Synthesis of Naphthoxazoles by Photocyclization of 4-/5-(Phenylethenyl)oxazoles

Article abstract of DOI:10.1002/ejoc.201800737

Promising test results on the biological activity of our previously described naphtho[1,2-d]oxazoles and heterobenz[1,2-d]oxazoles, obtained by the photochemical cyclization of 5-phenylethenyl- and 5-heteroarylethenyloxazoles, prompted us to continue with the photochemical synthesis of substituted naphtho[1,2-d]oxazoles, and to extend the photochemical cyclization to the synthesis of naphtho/heterobenz[2,1-d]oxazoles from 4-(aryl/heteroarylethenyl)oxazoles. The required p- and o-phenyl-substituted 5-arylethenyloxazoles were prepared from the corresponding α,β-unsaturated aldehydes and the TosMIC reagent (tosylmethyl isocyanide) by the Van Leusen reaction. The substituted 4-(aryl/heteroarylethenyl)oxazoles were prepared by the Wittig reaction starting from various phosphonium salts and 2-H/methyl-4-oxazolecarbaldehydes.

Full text of DOI:10.1002/ejoc.201800737

A Journal of
Accepted Article
Title: Synthesis of Naphthoxazoles by Photocyclization of 4-/5-
(phenylethenyl)oxazoles
Authors: Ivana Šagud, Marija Šindler-Kulyk, Irena Škorić, Vanja
Kelava, and Željko Marinić
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
Synthesis of Naphthoxazoles by Photocyclization of 4-/5-(phenylethenyl)oxazoles
Ivana Šagud*a, Marija Šindler-Kulyka, Irena Škorića, Vanja Kelavab and Željko Marinićc
aDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb,
Marulićev trg 19, 10000 Zagreb, Croatia, bFidelta Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia,
cNMR Center, Rudjer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
isagud@fkit.hr
Abstract graphic
Abstract
Promising test results on biological activity of our previously described naphtho[1,2-d]oxazoles
and heterobenz[1,2-d]oxazoles, obtained by photochemical cyclization of 5-phenylethenyl- and
5-heteroarylethenyloxazoles, prompted us to continue with the photochemical synthesis of
diverse substituted naphtho[1,2-d]oxazoles and extend the photochemical cyclization to
naphtho/heterobenz[2,1-d]oxazoles going from 4-(aryl/heteroarylethenyl)oxazoles. Required
p- and o-phenyl-substituted 5-arylethenyloxazoles were prepared from the corresponding ,-
unsaturated aldehydes and the TosMIC reagent by Van Leusen reaction. For the preparation of
the substituted 4-(aryl/heteroarylethenyl)oxazoles the Wittig reaction was used starting from
the selected diverse phosphonium salts and the 2-H/methyl-4-oxazolecarbaldehydes.
Keywords: polycyclic oxazoles, photocyclization, biological activity, Van Leusen, Wittig
reaction
Introduction
Benzoxazoles and naphthoxazoles as subunits are important moieties in the synthesis of
biologically active molecules[1-7] and there is a vast number of ground state synthetic
approaches leading to these fused oxazole polycyclic compounds.[8-15] One of the excited state
approaches for the formation of polycycles would be the photocyclization reaction. In the
specific case of heterobenzoxazoles and naphthoxazoles the required substrates would have to
be stilbene-type compounds. Earliest studies on excited state reactivity of stilbene were done
on the photochemical isomerization and cyclization reactions. Synthetically efficient
photocyclization became feasible in 1964, when F. Mallory discovered that iodine can catalyze
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this oxidation.[16] Over the preceding years there has been a lot of developments and
applications[17] of the Mallory photocyclization of heterostilbene-type analogues. The
photocyclization of heterostilbene-type compounds that would have an oxazole ring
incorporated into it was not described until our paper appeared covering photochemical
transformations of 5-arylethenyl-/5-heteroarylethenyloxazoles.[18] In the published Note an
easy and clean photochemical path to new fused naphtho[1,2-d]oxazoles as well as
heterobenzoxazoles was given. Since this paper was published some of the naphtho[1,2-
d]oxazoles as well as heterobenzoxazoles (A-G; figure 1) that were synthesized were tested for
antioxidant activity as well as acetylcholinesterase and butyrylcholinesterase inhibitory
activity.[19] These compounds have shown a high cholinesterase inhibition rate and antioxidant
activity greater than that of vitamin C. As acetylcholinesterase and butyrylcholinesterase hyper
production along with oxidative stress play a big role in different stages of Alzheimer’s disease
some of the tested compounds could potentially become promising hits in the search for a drug.
Figure 1. Biologically active naphtho[1,2-d]oxazoles and heterobenzoxazoles.
These previously synthesized fused oxazole compounds are also being tested for additional
biological activity, lipophilicity as well as metabolic stability.[20] Having in mind that these
structures are showing such positive results it was our goal to significantly broaden the scope
of this easy and fast photochemical synthesis by adding selected, new, naphtho[1,2-d]oxazoles
as well as a series of new naphtho[2,1-d]oxazoles and fused heterobenzoxazoles to the library
of compounds.
Results and discussion
Synthesis of the 4-/5-(phenylethenyl)oxazoles
The plan was to synthesize new 4-styryl/heteroaryl-oxazoles that would further be
photochemically transformed to heterobenz/naphtho[2,1-d]oxazole products. For the synthesis
of these 4-aryl/furyl/thienylethenyloxazoles Wittig reaction[21] was utilized. Selected
phosphonium salts (2-4) were combined with the oxazole-4-carbaldehyde (1a)[22] or 2-methyl-
oxazole-4-carbaldehyde (1b)[23] with sodium ethoxide as base (scheme 1). Aldehydes 1a and
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1b were prepared from commercially available esters by DIBAL-H reduction following the
procedure[23] for oxazole-4-carbaldehyde (1a).
Scheme 1. Synthesis of 4-styryloxazoles (5a-c; 6a-c; 7a,b) and 4-(2-methylstyryl)oxazoles
(5d; 6d-f; 7c,d).
Required phosphonium salts were synthesized from the corresponding bromides and
triphenylphosphine.[24-28] Phosphonium salt with the methoxy group in the para position on the
phenyl ring was used to give compounds 6a and 6d and the 2-furyl and 2-thienyl salts to give
compounds 7a-d, respectively. Salt with the methyl group in both the ortho and the para
position was used for the synthesis of compounds 5b, 6b and 6e, respectively. As biologically
active compounds containing heterocycles which are bearing nitro groups are well known[29]
a
salt with the nitro group in the para position of the phenyl ring was used for the synthesis of
compounds 6c and 6f. One of the groups that is also a proven pharmacophore is the nitrile
group.[30] Nitriles often play a key role as hydrogen bond acceptors thus bonding with the amino
acids or water which are bound to the protein backbone.[31,32] This group is also quite robust
and is not readily metabolized so it passes through the body unchanged and the release of the
cyanide from aromatic carbons has never been observed.[33] This prompted us to synthesize
compounds 5c and 5d where phosphonium salt with the o-nitrile group was utilized.
All of the Wittig reactions gave mixtures of trans and cis isomers in diverse ratios. The
geometry of the resulting alkene that is formed in the Wittig reaction depends partially on the
reactivity of the ylide. The formed ylide can be stabilized by bearing an electron withdrawing
group and not as reactive as when it has an electron donating group or an alkyl group. [34-36] The
overall stereoselectivity of the Wittig reaction is believed to be the result of steric effects
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European Journal of Organic Chemistry
that develop as the ylide and carbonyl compound approach one another. The three phenyl
substituents on phosphorus impose large steric demands that govern the formation of the
diastereomeric adducts. Reactions of unstabilized phosphoranes are believed to to be
selective for the cis-alkene. Ultimately the precise stereoselectivity is dependent on a
number of variables, including reactant structure, the base used for ylide formation, the
presence of other ions, solvent, and temperature. [37]
Wittig reaction with the (2-cyanobenzyl)triphenylphosphonium bromide (2b) was
stereoselective and only cis-5c and cis-5d were formed, respectively. While the (4-
nitrobenzyl)triphenylphosphonium bromide (3c) gave only trans-6c and trans-6f, respectively.
Both the cyano and the nitro group are by itself electron withdrawing, but when they are present
as substituents on the phenyl ring there are numerous electronic and steric effects that come
into consideration, and direct the Wittig reaction towards stereoselectivity. All of the other salts,
that were used, gave mixtures of isomers as products, with variable cis/trans ratios. New 4-
styryloxazoles 5-7 were obtained in good to excellent yields (23 – 98.5 %). Mixtures of isomers,
that had the Rf values different enough, were separated by multiple column and thin layer
chromatographies on silica gel with petroleumether/diethyl ether as eluent and they were
completely characterized (See experimental part and SI).
To further broaden the library of naphtho[1,2-d]oxazoles new 5-(arylethenyl)oxazoles were
synthesized, as described,[18] in one step by Van Leusen reaction[38,39] from the corresponding
aryl-substituted ,-unsaturated aldehydes (9a-e) with tosylmethyl-isocyanide (TosMIC)
(scheme 2).
Scheme 2. Synthesis of 5-(arylethenyl)oxazoles 10a-e.
After the solvent was evaporated and the crude reaction mixture purified by column
chromatography on silica gel, substituted 5-styryloxazoles (trans-10a-e) were isolated in yields
ranging from 22% to 94%. The trans-3-(o-tolyl)acrylaldehyde[40] (9a), that was not
commercially available, was synthesized by Wittig reaction from the o-methylbenzaldehyde (8)
and formylmethylenetriphenylphosphorane by a procedure described in literature for the
synthesis of (E)-3-(pyridyl)acrylaldehydes[41] (scheme 3).
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European Journal of Organic Chemistry
Scheme 3. Synthesis of trans-3-(o-tolyl)acrylaldehyde (trans-9a).
The stereoselectivity leading exclusively to trans-9a was directed by the electron withdrawing
CHO group on the ylide. With 1.3 equiv of the starting phosphorane the yield on the product
9a was 27% and an increase of the phosphorane added to the reaction (up to 3 equiv) gave no
rise in the yields of neither the desired product trans-3-(o-tolyl)acrylaldehyde (trans-9a) nor
the byproduct trans,trans-5-(2-methylphenyl)penta-2,4-dienal (trans,trans-11). Reduced
reactivity of the o-methylbenzaldehyde (8) can be explained by the steric hindrances of the
substituent in the ortho position. We have observed this effect of the ortho group in one of our
previous papers.[42] In that case the vinyl group was in the ortho position to the aldehyde and
that resulted in both a lower yield of formation of the acrylaldehyde as well as in formation of
the double addition byproduct. The selected new 5-styryloxazoles (10) were synthesized in
order to transform them to naphtho[1,2-d]oxazoles with chlorine, fluorine and dimethyl-amino
groups, as potential pharmachophores.[43,44] Fluorine and dimethyl-amino groups have been
extensively investigated as substituents in drug research as they can enhance biological activity
as well as chemical and metabolic stability.[45,46] As all of the ,-unsaturated aldehydes (9)
were in trans-configuration, when entering the Van Leusen reaction, all of the synthesized
compounds 10a-e were obtained in pure trans-form (See Experimental and SI).
Photochemical transformation of oxazole derivatives 5-10
From our previous studies on the photo-physical properties of 2/4/5-styryloxazoles[47,48] it is
evident that in the case of 4- and 5-styryl-oxazoles, the initial process in nitrogen purged
solutions is the trans-cis isomerization followed by the electrocyclization process to
naphthoxazoles via dihydro-intermediates. The electrocyclization process is accelerated in
solutions that are aerated, which is expected. Formation of the desired cyclization products in
preparative conditions with iodine present is fast and efficient because the iodine acts as a
hydrogen-trapping agent. This makes the photocyclization reaction of 4- and 5-styryloxazoles
useful and economic as a synthetic tool. Preparative irradiation experiments of 5-10 were
performed in toluene solutions with the addition of small amounts of iodine (≈1-3 mg) in the
Rayonet reactor equipped with 300 and 350 nm lamps, respectively (scheme 4). The irradiations
were performed until full consumption of the starting 4/5-(arylethenyl)oxazoles (schemes 4 and
5).
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Scheme 4. Photocyclization of 4-(arylethenyl)oxazoles to naphtho[2,1-d]oxazoles 12-13.
Scheme 5. Photocyclization of 5-(arylethenyl)oxazoles to naphtho[1,2-d]oxazoles 14.
Synthesized 4-(arylethenyl)oxazoles 5a-d and 6a-e as well as 5-(arylethenyl)oxazoles 10a-d
gave the photocyclization products 12-14 in very good to excellent yields, ranging from 30%
to 99%. Tables 1 and 2 give a summary of the starting compounds, cyclization products,
reaction conditions and the photocyclization reaction yields. All of the cyclization products
were isolated and completely characterized by spectroscopic methods (See Experimental part
and SI).
Table 1. Cyclization products 12-13 of 4-(arylethenyl)oxazoles 5 and 6.
Starting
tirr/
Yield
(%)
Product

irr/nm
Compound
h
4
4
300
92a
300
300
49
11
90
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11
300
35
7
4
300
300
350
90
65
86
16
7
7
300
300
350
45
53
42
24
a Lit. yield 14%51
Table 2. Cyclization products 14 of 5-(arylethenyl)oxazoles 10.
Starting
tirr/
Yield
Product

irr/nm
Compound
(%)
h
7
300
99
33
24
350
11
7
300
300
77
30
On irradiation of 4-(heteroarylethenyl)oxazoles 7a-d the resulting photo-mixtures showed only
trans-cis isomerization, in shorter irradiation times, and high molecular weight products on
prolonged irradiations. No photocyclization products were detected, not even in trace amounts
(scheme 6). As opposed to the formerly studied 5-(heteroarylethenyl)oxazoles[18] new 4-
(heteroarylethenyl)oxazoles 7a-d obviously do not cyclize under the same conditions.
Modification of the irradiation time, concentration, wavelength or the amount of iodine that
was added gave no improvement. Photocyclization reactivity of the 5- versus 4-
(heteroarylethenyl)oxazoles is comparable to the reactivity of the 1,2-di-(2-thienyl)ethene and
1,2-di-(3-thienyl)ethene where the 2-thienyl derivative gave the fused cyclization product in
70% yield and the 3-thienyl derivative gave no product.[49] It can also be compared to the
difference in reactivity of our previously published 5-(heteroarylethenyl)oxazole compounds
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
where the 5-(3-thienylethenyl)oxazole had a lower cyclization yield (41%) than the 5-(2-
thienylethenyl)oxazole (59%).[18] The position of the heteroatoms (4-oxazole vs 5-oxazole) in
the stilbene-type compounds has an effect on the overall distribution of electrons in the excited
[50]
state of the system and consequently this impacts the general reactivity. Recently,
the
stilbene-type derivatives with furan and thiophene moieties were studied under base conditions.
In the present paper we haven’t explored photocyclization conditions beyond neutral. The
compound 10e (scheme 6) with the -substituted chlorine atom also reacted by giving high
molecular weight products and traces of a large number of unidentified products.
Scheme 6. Attempted photocyclization of 7a-d and 10e.
At this time the cause of this unreactivity was not investigated further and these starting
compounds were proclaimed to be synthetically ineffective, but future study into their non-
reactivity is not excluded.
In an attempt to further open new routes for the formation of polycyclic heterocycle containing
compounds, 5-(2-vinylphenyl)oxazole (15) was synthesized by Van Leusen reactions starting
from 2-vinylbenzaldehyde (16). This compound, in which the middle double bond of the
hexatriene system is a part of a benzene ring, has a hypsochromic shift in UV spectrum (See
SI) when compared to the 2/4/5-styryloxazoles where the middle double bond of the hexatriene
system is a part of a conjugated system, as expected. Photocyclization reaction of compound
15 gave the identical product as the photocyclization of the 4-styryloxazole (5a) but via a
different cyclization route (scheme 7). We hypothesized that electrocyclization proceeds via
DH1 and DH2 followed by loss of hydrogen.
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European Journal of Organic Chemistry
Scheme 7. Plausible mechanism for the photocyclization of 15.
Conditions of this photocyclization reaction were considerably different. The irradiation was
performed in argon purged solutions without addition of iodine. The yield was smaller (16%)
than the one gained by photocyclization from 5a (92%) but never the less it is a new option for
insertion of oxazole ring into the polycyclic compounds.
CONCLUSION
In conclusion, new 4-(aryl/heteroarylethenyl)- (5-7) and 5-(arylethenyl)oxazoles (10) have
been synthesized and photochemically cyclized to various naphtho[2,1-d]oxazoles 12-13 and
naphtho[1,2-d]oxazoles 14, respectively. For the synthesis of the starting 4-aryl-/5-
heteroarylethenyloxazoles two synthetic methods were utilized, the Wittig reaction and the Van
Leusen reaction. All of the starting 4-aryl-/5-heteroarylethenyloxazoles are new compounds
and are completely characterized. The described photochemical method to substituted
naphtho[1,2-d]oxazoles and naphtho[2,1-d]oxazoles was proven to be applicable for the
synthesis of a broad spectrum of fused polycycles with the oxazole ring incorporated into the
system to be tested for biological activity. We have demonstrated that 4-
(heteroarylethenyl)oxazoles with furan and thiophene moiety behave radically different.
Additionally, we have presented a potential new photochemical route to naphtho[2,1-d]oxazole
on irradiation of 5-(o-vinylphenyl)oxazole.
Experimental section
General procedures. Petroleum ether, bp 40-60 ºC, was used. Solvents were purified by
distillation. Column chromatography was carried out on columns with silica gel (Fluka 0,063-
0,2 nm and Fluka 60 Å, tehnical grade). TLC was carried out using plates coated with silica gel
(0,2 mm, 0,5 mm, Kieselgel 60 F254). Organic layers were routinely dried with anhydrous
MgSO4 and evaporated using a rotary evaporator. 1H and 13C NMR spectra were recorded on a
spectrometer at 600 MHz. All NMR spectra were measured in CDCl3 using tetramethylsilane
as reference. The assignment of the signals is based on 2D-CH correlation and 2D-HH-COSY
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experiments. The following abbreviations are used: s, singlet; d, doublet; t, triplet; q, quartet,
dd, doublet of doublets; m, multiplet and br, broad. UV spectra were measured on a UV/VIS
spectrophotometer. IR spectra were recorded on a FTIR-ATR and FTIR. Mass spectra were
obtained on a GC-MS system. Melting points were obtained using a microscope equipped
apparatus and are uncorrected. HRMS analysis were carried out on a UHPLC/MS system with
the QTOF mass spectrometer operating at Dual AJS ESI, 2 GHz, Ext dynamic range and on a
mass spectrometer (MALDI TOF/TOF analyzer), equipped with Nd:YAG laser operating at
355 nm with firing rate 200 Hz in the positive (H+) or negative (-H) ion reflector mode.
Irradiation experiments were performed in closed quartz vessels in benzene or toluene solutions
in a photochemical reactor equipped with 300 and 350 lamps, respectively.
Synthesis of 4-styryloxazoles (5-6) and 4-(heteroarylethenyl)oxazoles (7)
Phosphonium salt (0.00217 mol) was dissolved in 50 mL of dry ethanol. In a funnel sodium
ethoxide was prepared by dissolving 0.06 g of sodium (1.2 eq, 0.0026 mol) in 20 mL of ethanol
and added dropwise to the reaction mixture, simultaneously with the 2-methyl-oxazole-4-
carbaldeyhde (1a)/oxazole-4-carbaldeyhde (1b) (1 eq, 0.00217 mol,), from a syringe. The
reaction mixture was left to stir for 24 h. Solvent was removed under reduced pressure and the
residue was dissolved in water and extracted with toluene (6 × 20 mL). Organic layers were
dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure.
Isomers were purified and separated by multiple column and thin layer chromatographies.
4-styryloxazole (5a)[39] (0.255 g, 56%))
cis-4-styryloxazole (cis-5a, with 11% of trans-5a as impurity) as oil: Rf (PE/E = 3:1) = 0.41;
IR max/cm-1: 3024, 1517, 1097, 1065, 910; UV (EtOH) λmax/nm (ε/dm3mol-1cm-1): 275 (8719);
1H NMR (CDCl3, 600 MHz): δ/ppm 7.78 (s, 1H, H-2), 7.38-7.33 (m, 5H, H-ar), 7.28 (s, 1H, H-
5), 6.72 (d, 1H, Jet = 12.0 Hz, H-et), 6.44 (d, Jet = 12.0 Hz, 1H, H-et); 13C NMR (CDCl3, 150
MHz) δ/ppm: 150.1 (d, C-2), 137.6 (s), 136.7 (s), 136.2 (d, C-5), 132.2 (d, C-et), 128.5 (d, C-
Ar), 128.3 (d, C-Ar), 127.6 (d, C-Ar), 120.0 (d, C-Ar); HRMS(MALDI-TOF/TOF) za
C11H9NO: (M+K)+calcd = 210.0316, (M+H)+found = 210.0311.
trans-4-styryloxazole (trans-5a) (Values are taken out of a spectra of mixture of the two
isomers) as oil: Rf (PE/E=3:1) = 0.40; 1H NMR (CDCl3, 600 MHz): δ/ppm 7.88 (s, 1H, H-2),
7.68 (s, 1H, H-5), 7.50 (d, Jar = 7.3 Hz, 1H, H-ar), 7.38-7.33 (m, 2H, H-ar), 7.36 (d, Jet = 16.0
Hz, H-et), 7.29-7.28 (m, 1H, H-ar), 6.94 (d, Jet = 12.0 Hz, 1H, H-et).
4-(2-methylstyryl)oxazole (5b) (0.157 g, 39%)
cis-4-(2-methylstyryl)oxazole (cis-5b) as oil: Rf (PE/CH2Cl2 = 3:1) = 0.40; UV (EtOH)
λmax/nm (ε/dm3mol-1cm-1): 271 (5488); 1H NMR (CDCl3, 600 MHz) δ/ppm: 7.73 (s, 1H, H-2),
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7.24-7.18 (m, 3H, H-Ar), 7.19-7.17 (m, 1H, H-Ar), 6.88 (s, 1H, H-5), 6.74 (d, Jet = 11.9 Hz,
1H, H-et), 6.54 (d, Jet = 11.9 Hz, 1H, H-et), 2.24 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz)
δ/ppm: 149.4 (d, C-2), 137.0 (s), 136.3 (s), 135.4 (d, C-5), 135.1 (s), 131.0 (d, C-et), 129.8 (d,
C-Ar), 127.6 (d, C-Ar), 127.3 (d, C-Ar), 125.6 (d, C-Ar), 120.8 (d, C-et), 19.1 (q, CH3); MS
m/z (%, fragment): 185 (100%, M+), 168 (18%), 156 (27%); HRMS(MALDI-TOF/TOF) za
C12H11NO: (M+H)+calcd = 186.0913, (M+H)+found = 186.0916.
trans-4-(2-methylstyryl)oxazole (trans-5b) as oil: Rf (PE/CH2Cl2 = 3:1) = 0.45; IR max/cm-1:
1
3022, 1695, 1516, 1186, 1066; UV (EtOH) λmax/nm (ε/dm3mol-1cm-1): 283 (12819); H NMR
(CDCl3, 600 MHz): δ/ppm 7.87 (s, 1H, H-2), 7.65 (s, 1H, H-5), 7.58 (d, 1H, Jet = 15.8 Hz, H-
et), 7.55-7.54 (m, 1H, H-ar), 7.24-7.16 (m, 3H, H-ar), 6.83 (d, 1H, Jet = 15.8 Hz, H-et), 2.44 (s,
3H, CH3); 13C NMR (CDCl3, 150 MHz): δ/ppm 150.7 (d, C-2), 138.5 (s), 135.6 (s), 135.3 (s),
134.9 (d, C-5), 130.0 (d, C-ar), 128.2 (d, C-6/7), 127.3 (d, C-ar), 125.6 (d, C-ar), 124.7 (d, C-
ar), 116.7 (d, C-6/7), 19.4 (q, CH3); MS m/z (%, fragment): 185 (100%, M+), 168 (18%), 156
(27%).
4-(2-cyanostyryl)oxazole (5c) (0.415, 97%)
cis-4-(2-cyanostyryl)oxazole (cis-5c) as white powder: mp 99-1010C, (PE/E = 5:1) = 0.55, UV
(EtOH) max/nm (/dm3mol-1cm-1): 228 (12847), 272 (5402), 301 (Sh 3552), IR max/cm-1
(NaCl): 3147, 3112, 2924, 2228, 1736, 1519, 1478, 1450, 1090, 1H NMR (CDCl3, 600 MHz):
δ/ppm 7.76 (s, 1H, Hox2), 7.69 (d, J3/4= 7.6 Hz, 1H, Har4), 7.62 (d, J1/2 = 7.7 Hz, 1H, Har1), 7.55
(dd, J2/3 = 7.6 Hz, J1/2 = 7.7 Hz, 1H, Har2), 7.37 (t, J3/4 = J2/3 = 7.6 Hz, 1H, Har3), 7.35 (s, 1H,
Hox5) 6.80 (d, Jet = 12.1 Hz, 1H, Het), 6.66 (d, Jet = 12.2 Hz, 1H, Het); 13C NMR (CDCl3, 150
MHz): /ppm 150 (d, C-2), 140.7 (s), 136.7 (d), 132.2 (d), 131.8 (d), 129. 2 (d), 127.4 (d), 126.7
(d), 122.2 (d), 117.2 (s), 111.8 (s); MS m/z (%, fragment): 196 (100%, (M+H)+); HRMS (Q-
TOF) for C12H8N2O: (M+H)+calcd = 197.0637found = 197.0707.
2-methyl-4-(2-cyanostyryl)oxazole (5d) (0.210, 46 %)
cis-2-methyl-4-(2-cyanostyryl)oxazole (cis-5d) as oil: Rf (PE/E = 5:1) = 0.60; UV (EtOH)

max/nm (/dm3mol-1cm-1): 284 (4406); IR max/cm-1 (NaCl): 2926, 2224, 1589, 1109; 1H NMR
(CDCl3, 600 MHz): δ/ppm 7.67 (t, Jar = 8.8 Hz, 2H, Har1/4), 7.55-7.52 (m, 1H, Har2-3), 7.37 (t,
Jar = 8.8 Hz, 1H, Har2/3), 7.16(s, 1H, Hox), 6.74 (d, Je t= 12.1 Hz, 1H, Het), 6.58 (d, Jet = 12.1 Hz,
1H, Het), 2.38 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 160.5 (s), 140.8 (s), 136.2 (d,
C-ar), 132.3 (d, C-ar), 131.8 (d, C-ar), 129.2 (d, C-ar), 127.3 (d, C-ar), 126.0 (d, C-et), 122.9
(d, C-et), 117.3 (s(, 111.8 (s), 13.3 (q, CH3); MS m/z (%, fragment): 211 (100%, (M+H)+);
HRMS (Q-TOF) for C14H10N2O: (M+H)+calcd = 211.0793, (M+H)+found = 211.0866.
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4-(4-methoxystyryl)oxazole (6a) (0.180 g, 41%)
cis-4-(4-methoxystyryl)oxazole (cis-6a) as oil: Rf (PE/E = 20:1) = 0.63, UV (EtOH) max/nm
(/dm3mol-1cm-1): 272 (6306); IR max/cm-1 (NaCl): 2933, 1607, 1509, 1252,1H NMR (CDCl3,
600 MHz): δ/ppm 7.79 (s, 1H, Hox2), 7.38 (s,1H, Hox5), 7.34 (d, Jar = 8.7 Hz, 2H, Har2), 6.87 (d,
Jar1 = 8.7 Hz, 2H, Har1), 6.63 (d, Jet = 12.1 Hz, 1H, Het), 6.34 (d, Jet =12.1 Hz, 1H, Het), 3.83 (s,
3H, OCH3); 13C NMR (CDCl3, 150 MHz): /ppm 159.1 (s), 151.1 (s), 150.1 (d, C-ox2), 136.9
(s), 136.1 (d, C-et), 131.8 (d, C-ox5), 130.0 (d, C-ar2), 118.5 (d, C-et), 113.8 (d, C-Ar1), 55.2
(q, OCH3); MS m/z (%, fragment): 201 (100%), (M+H)+); HRMS (Q-TOF) for C12H11NO2:
(M+H)+calcd = 202.0790, : (M+H)+found = 202.0863.
0
trans-4-(4-methoxystyryl)oxazole (trans-6a) as white powder: mp 95-101 C, Rf (PE/E =
20:1) = 0.55; UV (EtOH) max/nm (/dm3mol-1cm-1): 292 (8199); IR max/cm-1(NaCl): 2913,
1
1733, 1606, 1511, 1249; H NMR (CDCl3, 600 MHz): δ/ppm 7.86 (s, 1H, Hox2), 7.64 (s, 1H,
Hox5), 7.43 (d, Jar= 8.6 Hz, 2H, Har2), 7.29 (d, Jet = 15.9 Hz, 1H, Het), 6.89 (d, Jar = 8.6 Hz, 2H,
Har1), 6.81 (d, Jet = 15.9 Hz, 1H, Het), 3.83 (s, 3H, OCH3), MS m/z (%, fragment): 201 (100%,
M+).
4-(4-methylstyryl)oxazole (6b) (0.150 g, 37%)
4-(4-methylstyryl)oxazole) as an inseparable mixture of cis and trans-isomer: Rf (PE/E = 20:1)
= 0.60; IR max/cm-1(NaCl): 3023, 1694, 1514, 1090; 1H NMR (CDCl3, 600 MHz, from mixture
for cis-6b): δ/ppm 7.87 (s, 1H, Hox2), 7.66 (s, 1H, Hox5), 7.39 (d, Jet = 7.7 Hz, 2H, Har), 7.32 (d,
Jar = 16.0 Hz, 1H, Het), 7.16 (dd, Jar = 7.2 Hz, 2H, Har), 6.88 (d, Jar = 16.0 Hz, 1H, Het), 2,36 (s,
1
3H, CH3); H NMR (CDCl3, 600 MHz, from mixture for trans-6b): δ/ppm ppm 7.78 (s, 1H,
Hox2), 7.34 (s, 1H, Hox5), 7.27 (d, Jet = 7.2 Hz, 2H, Har), 7.16 (dd, Jar = 7.2 Hz, 2H, Har), 6.67 (d,
Jet = 11.6 Hz, 1H, Het), 6.39 (d, Jar = 11.6 Hz, 1H, Het), 2,36 (s, 3H, CH3; MS m/z (%, fragment):
185 (100%, M+), 168 (18%), 156 (27%); HRMS(Q-TOF) for C12H11NO: (M+H)+
186.0841, (M+H)+found = 186.0914.
=
calcd
4-(4-nitrostyryl)oxazole (6c) (0.402 g, 86%)
cis-4-(4-nitrostyryl)oxazole (cis-6c) as yellow powder: mp 171-1780C, (PE/E = 20:1) = 0.43;
UV (EtOH) max/nm (/dm3mol-1cm-1): 328 (8320); IR max/cm-1(NaCl): 3125, 2925, 2854,
1
1596, 1508, 1341, 1090, H NMR (CDCl3, 600 MHz): δ/ppm 8.19 (d, Jar = 8.8 Hz, 2H, Har2),
7.82 (s, 1H, Hox2), 7.63 (d, Jar = 8.8 Hz, 2H, Har1), 7.49 (s, 1H, Hox5), 6.67 (d, Jet = 12.6 Hz, 1H,
13
Het2), 6.57 (d, Jet = 12.6 Hz, 1H, Het1); C NMR (CDCl3, 150 MHz): /ppm 150.7 (d, Cox2),
146.9 (s), 143.9 (s), 137.5 (d, Cox2), 136.5 (s), 129.8 (d, Car1), 129.4 (d, Cet1), 124.2 (d, Car2),
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121.5 (d, Cet2); MS m/z (%, fragment): 216 (100%); (M+H)+); HRMS (Q-TOF) for C11H8N2O3:
(M+H)+ calcd 217.0535, found 217.0610.
trans-4-(4-nitrostyryl)oxazole (trans-6c) as oil: (PE/E = 20:1) = 0.15; UV (EtOH) max/nm
1
(/dm3mol-1cm-1): 339 (9634); IR max/cm-1(NaCl):2923, 1735, 1594, 1507, 1341, H NMR
(CDCl3, 600 MHz): δ/ppm 8.21(d, Jar = 8.7 Hz, 2H, Har), 7.91 (s, 1H, Hox2), 7.76 (s, 1H, Hox5),
7.61 (d, Jar = 8.7 Hz, 2H, Har), 7.41 (d, Jet = 15.6 Hz, 1H, Het), 7.10 (d, Jet = 15.6 Hz, 1H, Het);
13C NMR (CDCl3, 150 MHz): /ppm 146.6 (d, C-ox2), 142.7 (s), 135.4 (s), 129.3 (s), 128.0 (d,
C-et), 126.5 (d, C-ar), 123.6 (d, C-ar), 122.1 (d, C-ox5), 119.9 (d), 112.0 (d); MS m/z (%,
fragment): 216 (100%); (M+H)+.
2-methyl-4-(4-methoxystyryl)oxazole (6d) (0.460 g, 98.5 %)
cis-2-methyl-4-(4-methoxystyryl)oxazole (cis-6d) as oil: Rf (PE/E = 20:1) = 0.80; UV (EtOH)

max/nm (/dm3mol-1cm-1): 284 (6796), 394 (Sh 850); IR max/cm-1(NaCl): 2887, 1605, 1516,
1343, 1228; 1H NMR (CDCl3, 600 MHz): δ/ppm 7.35 (d, Jar = 8.7 Hz, 2H, Har2), 7.25 (s, 1H,
Hox), 6.86 (d, Jar = 8.7 Hz, 2H, Har1), 6.56 (d, Jet = 12.4 Hz, 1H, Het), 6 27 (d, Jet = 12.4 Hz, 1H,
Het), 3.83 (s, 3H, OCH3), 2.41 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 159.9 8 (s),
158.5 (s), 136.7 (s), 135.1 (d, C-ox), 130.6 (d, C-et), 129.5 (s), 129.3 (d, C-ar), 118.6 (d, C-et),
113.3 (d, C-ar), 54.7 (q, OCH3), 13.3 (q, CH3); MS m/z (%, fragment): 216 (100%); (M+H)+.
trans-2-methyl-4-(4-methoxystyryl)oxazole (trans-6d) as white powder: mp 113-117 0C; Rf
(PE/E = 20:1) = 0.23; UV (EtOH) max/nm (/dm3mol-1cm-1): 286 (Sh 10088), 293 (10348), 310
(Sh 6869), 322 (Sh 4381); IR max/cm-1 (NaCl): 2924, 1605, 1510, 1247; 1H NMR (CDCl3, 600
MHz): δ/ppm 7.49 (s, 1H, Hox), 7.41 (d, Jar = 8.7 Hz, 2H, Har), 7.22 (d, Jet = 15.9 Hz, 1H, Het),
6.87 (d, Jar = 8.7 Hz, 2H, Har), 6.74 (d, Jet = 15.9 Hz, 1H, Het), 3,82 (s, 3H, OCH3), 2.48 (s, 3H,
CH3); 13C NMR (CDCl3, 150 MHz): /ppm 161.3 (s), 158.9 (s), 138.9 (s), 134.1 (d, C-5), 129.3
(s), 129.1 (d-et), 127.2 (d-ar), 113.6 (d-et), 113.3 (d-ar), 54.8 (q, OCH3), 13.5 (q, CH3). MS m/z
(%, fragment): 216 (100%), (M+H)+).
2-methyl-4-(4-methylstyryl)oxazole (6e) (0.172 g, 40%)
cis-2-methyl-4-(4-methylstyryl)oxazole (cis-6e) as oil: (PE/E = 20:1) = 0.40; UV (EtOH)

max/nm (/dm3mol-1cm-1): 308 (2224); 1H NMR (CDCl3, 600 MHz): δ/ppm 7.28 (d, Jar = 8.0
Hz, 2H, H-ar), 7.19 (s, 1H, H-5), 7,13 (d, Jar = 8.0 Hz, 2H, H-ar), 6.60 (d, Jet = 12.5 Hz, 1H,
Het), 6.31 (d, Jet = 12.5 Hz, 1H, Het) 2.40 (s, 3H, CH3), 2.35 (s, 3H, CH3); MS m/z (%, fragment):
199 (100%, M+); HRMS (Q-TOF) for C13H13NO: (M+H)+
200.1071.
= 200.0997, (M+H)+
=
calcd
found
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
trans-2-methyl-4-(4-methylstyryl)oxazole (trans-6e) as white powder: mp 99-101 0C, (PE/E
= 20:1) = 0.43; UV (EtOH) max/nm (/dm3mol-1cm-1): 282 (27358), 290 (28184), 311 (Sh
14359); IR max/cm-1 (NaCl): 3088, 1726, 1591, 1097, 963; 1H NMR (CDCl3, 600 MHz): δ/ppm
7.51 (s, 1H, H5), 7.37 (d, Jar = 7.9 Hz, 2H, Har), 7.23(d, Jet = 16.1 Hz, 1H, Het), 7.14 (d, Jar = 7.9
Hz, 2H, Har), 6.83 (d, Jet = 16.1 Hz, 1H, Het), 2.48 (s, 3H, CH3), 2.35 (s, 3H, CH3); 13C NMR
(CDCl3, 150 MHz): /ppm 138.8 (s), 137.1 (s), 134.4 (d,C-5), 133.7 (s), 129.5 (d, C-et), 128.9
(d, C-ar), 125.9 (d, C-ar), 115.0 (d, C-et), 20.7 (q), 13.5 (q); MS m/z (%, fragment): 199 (100%,
M+).
2-methyl-4-(4-nitrostyryl)oxazole (6f) (0.352, 70.5 %)
trans-2-methyl-4-(4-nitrostyryl)oxazole (trans-6f) as yellow powder, mp 181-199 0C, (PE/E
= 20:1) = 0.15; UV (EtOH) max/nm (/dm3mol-1cm-1): 238 (7592), 343 (10915); IR max/cm-1
(NaCl): 2950, 1600, 1520, 1350; 1H NMR (CDCl3, 600 MHz): δ/ppm 8.20 (d, Jar = 8.8 Hz, 2H,
Har2), 7.62 (s, 1H, H5), 7.59 (d, Jar = 8.8 Hz, 2H, Har1), 7.33 (d, Jet = 16.0 Hz, 1H, Het1), 7.04 (d,
Jet = 16.0 Hz, 1H, Het2), 2.51(s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 162.3 (s), 146.9
(s), 138.5 (s), 136.7 (d, C-ox), 129.8 (s), 127.7 (d, C-et1), 126.8 (d, C-ar1), 124.1 (d, C-ar2),
120.9 (d, C-et2), 29.7 (CH3); MS m/z (%, fragment): 230 (100%), (M+H)+); HRMS (Q-TOF)
for C13H10N2O3: (M+H)+calcd = 231.0691, (M+H)+found = 231.0760.
4-(2-furostyryl)oxazole (7a) (0.097 g, 23 %)
cis-4-(2-furostyryl)oxazole (cis-7a) as oil: (PE/E = 20:1) = 0.35; UV (EtOH) max/nm
1
(/dm3mol-1cm-1): 305 (9623), 315 (8325); H NMR (CDCl3, 600 MHz): δ/ppm ppm 8.32 (s,
1H, H2), 7.87 (s, 1H, H5), 7.49 (d, Jf = 1.3 Hz, 1H, Hf1), 6.65 (d, Jf = 3.3 Hz, 1H, Hf3), 6.46-6.45
13
(m, 1H, Hf2), 6.37 (d, Jet = 13.2 Hz, Het), 6.26 (d, Jet = 13.2 Hz, Het); C NMR (CDCl3, 150
MHz): /ppm 152.1 (s), 150.1 (d), 142.3 (d), 137.7 (d), 136.7 (s), 117.3 (d), 115.5 (d), 112.1
(d), 111.8 (d); MS m/z (%, fragment): 161 (100%), (M)+); HRMS (Q-TOF) for C9H7NO2:
(M+H)+calcd = 162.0477, (M+H)+found = 162.0552.
trans-4-(2-furostyryl)oxazole (trans-7a) (from mixture of cis : trans = 1:1) (PE/E = 20:1) =
1
0.34; IR max/cm-1(NaCl): 3583, 1666,01595, 1359; H NMR (CDCl3, 600 MHz): δ/ppm 7.85
(s, 1H, H2), 7.65 (s, 1H, H5), 7.40 (d, Jf = 1.3 Hz, 1H, Hf1), 7.13 (dd, Jet = 15.7 Hz, Het), 6.42-
6.41 6.86 (d, Jet= 15.7 Hz, 1H, Het), 6.39-6.38 (m, 1H, Hf2t), 6.36 (s, 1H, Hf3); MS m/z (%,
fragment): 16 (100%).
4-(2-thienostyryl)oxazole (7b) (0.111 g, 29%)
cis-4-(4-thienostyryl)oxazole (cis-7b with 30% of trans-7b as impurity) as oil: (PE/E = 20:1)
= 0.41; UV (EtOH) max/nm (/dm3mol-1cm-1): 287 (Sh 4665), 299 (5119), 314 (Sh 3909); IR
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10.1002/ejoc.201800737
European Journal of Organic Chemistry

max/cm-1(NaCl): 2965, 1692, 1484, 1068; 1H NMR (CDCl3, 600 MHz): δ/ppm 8.32 (s, 1H, H2),
7.86 (s, 1H, H5), 7.49 (brs, 1H, Htf1), 6.46 (d, Jtf = 3.3 Hz, 1H, Htf3), 7.41-7.40 (m, 1H, Htf2),
6.37 (d, Jet = 13.1 Hz, 1H, Het), 6.25 (d, Jet = 13.1 Hz, 1H, Het); 6.80 (d, Jet = 12.1 Hz, 1H, Het),
6.66 (d, Jet = 12.2 Hz, 1H, Het); MS m/z (%, fragment): 161 (100%), (M)+).
trans-4-(4-thienostyryl)oxazole (trans-7b) as white powder: mp 100-103 0C, (PE/E = 20:1) =
1
0.40, UV (EtOH) max/nm (/dm3mol-1cm-1): 285 (Sh 8276), 293 (10907), 310 (Sh 8890); H
NMR (CDCl3, 600 MHz): δ/ppm 7.85 (s, 1H, H2), 7.64 (s, 1H, H5), 7.39 (d, Jtf = 1.7 Hz, 1H,
Htf1), 7.55 (d, Jet= 15.8 Hz, 1H, Het), 6.85 (d, Jet= 15.8 Hz, 1H, Het), 6.42-6.41 (m, 1H, Htf2),
6.35 (d, Jtf = 3.3 Hz, 1H, Htf3); 13C NMR (CDCl3, 150 MHz): /ppm152.3 8d), 150.7(s), 141.5
(d), 148.5 (s), 134.8 (d), 118.2 (d), 114.0 (d), 111.1 (d), 108.9 (d); MS m/z (%, fragment): 161
(100%), (M)+).
2-methyl-4-(2-furostyryl)oxazole (7c) (0.170 g, 37.5 %)
cis-2-methyl-4-(4-furostyryl)oxazole (cis-7c) as oil: (PE/E = 20:1) = 0.39; UV (EtOH)

max/nm (/dm3mol-1cm-1): 290 (Sh 7821), 302 (9591), 316 (7325); IR max/cm-1(NaCl): 3047,
2930, 1759;1H NMR (CDCl3, 600 MHz): δ/ppm 8.16 (s, 1H, H5), 7.46 (d, Jf = 1.5 Hz, 1H, Hf1),
6.67 (d, Jf = 3.3 Hz, 1H, Hf3), 6.45-6.44 (m, 1H, Hf2), 6.31 (d, Jet = 12.9 Hz, 1H, Het), 6.17 (d,
Jet = 12.9 Hz, 1H, Het), 2.47 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 160.5 (s), 152.3
(s), 142.1 (d), 137.3 (d), 137.0 (s), 116.8 (d), 115.8 (d), 111.8 (d), 111.7 (d), 13.7 (q); MS m/z
(%, fragment): 175 (100%), (M)+); HRMS (Q-TOF) for C10H9NO2: (M+H)+
(M+H)+found = 176.0703.
= 176.0633,
calcd
trans-2-methyl-4-(4-furostyryl)oxazole (cis-7c) as oil: (PE/E = 20:1) = 0.45, UV (EtOH)
1

max/nm (/dm3mol-1cm-1): 286 (13774), 298 (18327), 312 (14789); H NMR (CDCl3, 600
MHz): δ/ppm 7.50 (s, 1H, H5), 7.37 (d, Jf = 1.3 Hz, 1H, Hf1), 7.06 (d, Jet = 15.9 Hz, 1H, Het),
6.79 (d, Jet = 15.9 Hz, 1H, Het), 6.40-6.39 (m, 1H, Hf2), 6.31 (d, Jf = 3.1 Hz, 1H, Hf3), 2.48 (s,
3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 157.0 (s), 155.2 (s), 142.2 (s), 138.9 (s), 135.2
(d), 117.9 (d), 114.9 (d), 111.6 (d), 109.0 (d), 13.9 (q); MS m/z (%, fragment): 175 (100%),
(M)+).
2-methyl-4-(2-thienostyryl)oxazole (7d) (0.111 g, 45%)
cis-2-methyl-4-(4-thienostyryl)oxazole (cis-7d)(from a mixture of isomers, cis : trans = 3 : 1)
1
as oil: (PE/E = 20:1) = 0.23; IR max/cm-1(NaCl): 3104, 1672, 1587, 1371, 1105; H NMR
(CDCl3, 600 MHz): δ/ppm 1H NMR (CDCl3, 600 MHz): δ/ppm 7.63 (s, 1H, H5), 7.28 (d, Jtf =
3.6 Hz, 1H, Htf1), 7.25 (d, Jtf = 6.0 Hz, 1H, Htf3), 7.0-6.97 (m, 1H, Htf2), 6.65 (d, Jet = 12.3 Hz,
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
1H, Het), 6.23 (d, Jet = 12.3 Hz, 1H, Het), 2.48 (s, 3H, CH3); MS m/z (%, fragment): 192 (100%),
(M+H)+); HRMS (Q-TOF) for C10H9NOS: (M+H)+calcd = 192.0405, (M+H)+found = 192.0480.
trans-2-methyl-4-(4-thienostyryl)oxazole (trans-7d) (from a mixture of isomers, cis : trans =
3 : 1) as oil: (PE/E = 20:1) = 0.23; 1H NMR (CDCl3, 600 MHz): δ/ppm 1H NMR (CDCl3, 600
MHz): δ/ppm 7.50 (s, 1H, H5), 7.17 (d, Jtf = 5.0 Hz, 1H, Htf1), 7.04 (d, Jtf = 3.3 Hz, 1H, Htf3),
7.0-6.97 (m, 1H, Htf2), 6.69 (d, Jet = 15.7 Hz, 1H, Het), 6.39 (d, Jet = 15.7 Hz, 1H, Het), 2.48 (s,
3H, CH3).
Synthesis of 9a
trans-3-(2-methylphenyl)prop-2-enal (9a) was prepared from the o-methylbenzaldehyde and
formylmethylenetriphenylposphorane by the Wittig reaction described in literature.41
Formylmethylenetriphenylposphorane (1,3 eq, 0,026 mol) and aldehyde (1 eq, 0,02 mol) were
mixed in dry benzene and heated to reflux under a stream of nitrogen for 24h. After removal of
the solvent the crude residue was extracted with cold ether and the ether extracts were dried
over anhydrous MgSO4 after which the solvent was evaporated. The crude mixture contained
the compound 9 as well as the byproduct trans,trans-5-(2-methylphenyl)penta-2,4-dienal 11
and was purified by column chromatography on silica gel using petroleum ether/diethyl ether
(variable ratio) as eluent.
(0.79 g, 27%) trans-3-(2-methylphenyl)prop-2-enal[40] (trans-9a) as oil: R(f) (PE/E = 50:1) =
0.20; UV (EtOH) max/nm (/dm3mol-1cm-1): 292 (18898), 224 (9193); IR max/cm-1: 1677
1
(C=O), 1616, 1460, 1117; H NMR (CDCl3, 600 MHz) /ppm: 9.73 (d, JCHO,2 = 7.6 Hz, 1H,
CHO), 7.78 (d, J2,3 = 15.8 Hz, 1H, H-3), 7.59 (d, Jar = 7.8 Hz, 1H, H-Ar), 7.33 (dd, Jar = 7.6 Hz,
Jar = 7.2 Hz, 1H, H- Ar), 7.26 (dd, Jar = 7.6 Hz, Jar = 7.8 Hz, 2H, H-Ar), 6.67 (dd, JCHO,2 = 7.6
Hz, J2,3 = 15.8 Hz, 1H, H-2), 2.48 (s, 3H, CH3); 13C NMR (150 MHz, CDCl3): /ppm 193.3 (d,
CHO), 149.7 (d, C-3), 137.4 (s), 132.4 (s), 130.5 (d, C-ar), 129.2 (d, C-2), 126.3 (d, C-ar), 126.1
(d, C-ar), 19.2 (q, CH3); MS m/z (EI) = 147 (100, M+); HRMS(MALDI-TOF/TOF) for C10H10O:
(M+H)+calcd = 147.0804, (M+H)+found = 147.0801.
(0.098 g, 6%) trans,trans-5-(2-methylphenyl)penta-2,4-dienal (trans-11) as oil: R(f)
(PE/E=25:1) = 0.10; UV (EtOH) max/nm (/dm3mol-1cm-1): 329 (27012), 238 (6519); IR
1

max/cm-1: 3020, 1680 (C=O), 1616, 1599, 1157, 1119; H NMR (CDCl3, 600 MHz) : /ppm
9.63 (d, JCHO,2 = 7.9 Hz, 1H, CHO), 7.58 (d, Jar = 7.8 Hz, 1H, H-ar), 7.31 (dd, J2,3 = 15.4 Hz,
J3,4 = 11.0 Hz 1H, H-3), 7.28 (d, J4,5 = 15.4 Hz, 1H, H-5), 7.25 – 7.18 (m, 3H, H-ar), 6.93 (dd,
J3,4 = 11.0 Hz, J4,5 = 15.4 Hz, 1H, H-4), 6.28 (dd, J2,3 = 15.4 Hz, JCHO,2 = 7.9 Hz, 1H, H-2), 2.42
(s, 3H, H-CH3); 13C NMR (CDCl3, 150 MHz)  193.0 (d, CHO), 151.8 (d, C-3), 139.5 (d, C-
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
5), 136.4 (s), 134.0 (s), 131.0 (d, C-2), 130.3 (d, C-ar), 129.0 (d, C-ar), 126.7 (d, C-4), 125.9 (d,
C-ar), 125.4 (d, C-ar), 19.2 (q, CH3); HRMS (MALDI-TOF/TOF) for C12H12O: (M-e)-calcd
172.0883 (M-e)-found = 172.0878.
=
Synthesis of 5-(aryl/heteroarylethenyl)oxazoles (10a-e) and 15
Compounds 10a-e were prepared from the corresponding acrylaldehydes 9a-e and 4 -
toluenesulfonylmethyl isocyanide (TosMIC) as described in the literature for 5-
phenyloxazole.38 For the compound 15 the starting aldehyde was the o-vinylbenzaldehyde. 4-
Toluenesulfonylmethylisocyanide (1 eq, 0.005 mol), aldehyde (1 eq, 0.005 mol), and potassium
carbonate (1 eq, 0.005 mol) in 30 mL of methanol were heated under reflux for 3-4 h. After
removal of the solvent the residue was worked up with ice-water and extracted with cold ether.
Ether extracts were dried over anhydrous MgSO4. Evaporation under reduced pressure afforded
the crude product, which was further purified by column chromatography on silica gel using
petroleum ether/diethyl ether (variable ratio) as eluent.
trans-5-(2-methylstyryl)oxazole (trans-10a)
(0.31 g, 33%), as oil: Rf (PE/E=10:1) = 0.15; UV (EtOH) max/nm (/dm3mol-1cm-1): 300
(12646), 318 (11021), 329 (6440); IR max/cm-1: 3020, 2924, 1689, 1460, 1090, 955; 1H NMR
(CDCl3, 600 MHz): /ppm 7.82 (s, 1H, H-2), 7.51 – 7.5 (m, 1H, H-Ar), 7.33 (d, Jet = 16.2 Hz,
1H, H-et), 7.20 -7.14 (m, 3H, H-ar), 7.04 (s, 1H, H-4), 6.80 (d, Jet = 16.2 Hz, 1H, H-et), 2.43
(s, 3H, H-CH3); 13C NMR (CDCl3, 150 MHz): /ppm 150.6 (d, C-2), 150.2 (s,), 136.0 (s), 135.0
(d,C-ar), 128.2 (d, C-ar), 127.9 (d, C-et), 126.2 (d, C-ar), 125.0 (d, C-ar), 123.8 (d, C-5), 113.8
(d, C-et), 19.7 (s); HRMS(MALDI-TOF/TOF) for C12H11NO: (M+H)+
(M+H)+found = 186.0914.
= 186.0913,
calcd
trans-5-(4-N,N-dimethylaminostyryl)oxazole (trans-10b)
(0.235 g, 22 %) as yellow crystals: mp 139-141 °C; Rf (PE/E=1:1) = 0.20; UV (EtOH) max/nm
(/dm3mol-1cm-1): 357 (27584); IR max/cm-1: 2853, 2218, 1600, 1380, 1270; 1H NMR (CDCl3,
600 MHz): /ppm 7.80 (s, 1H, H-2), 7.38 (d, Jar = 8.7 Hz, 2H, H-ar), 7.03 (d, Jet =16.3 Hz, 1H,
H-et), 6.98 (s, 1H, H-4), 6.72 (d, Jet =16.3 Hz, 1H, H-et), 6.27-6.70 (m, 1H, H-ar), 3.00 (s, 6H,
N-(CH3)2); 13C NMR (CDCl3, 150 MHz): /ppm151.3 (s), 149.7 (s), 149.6 (d), 130.6 (d), 127.8
(d), 122.4 (d), 112.3 (d), 108.6 (s), 40.3 (q), 31.2 (q); MS m/z (EI) = 214 (100, M+); HRMS(Q-
TOF) for C13H14N2O: (M+H)+calcd = 215.1106, (M+H)+found = 215.1176.
trans-5-(4-chlorostyryl)oxazole (trans-10c)
(0.946 g, 92 %) as colorless crystals: mp 78-81°C; Rf (PE/E=10:1) = 0.55; UV (EtOH) max/nm
(/dm3mol-1cm-1): 299 (27977), 312 (29351), 326 (20895); IR max/cm-1: 1697, 1610, 1491,
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
1089; 1H NMR (CDCl3, 600 MHz): /ppm 7.84 (s, 1H, H-2), 7.40 (dd, Jar= 8.5 Hz, Jar= 6.6 Hz,
2H, H-ar), 7.33 (dd, Jar= 8.5 Hz, Jar= 6.6 Hz, 2H, H-ar), 7.08 (s, 1H, H-4), 7.04 (d, Jet = 16.2
Hz, 1H, H-et), 6.88 (d, Jet = 16.2 Hz, 1H, H-et); 13C NMR (CDCl3, 150 MHz): /ppm 149.9 (d,
C-2), 149.7 (s), 134.2 (s), 133.5 (s), 128.5 (d), 128.4 (d), 127.2 (d), 124.0 (d), 112.9 (d); MS
m/z (EI) = 205 (100, M+); HRMS(Q-TOF) for C11H8ClNO: (M+H)+
(M+H)+found = 206.0369.
= 206.0294,
calcd
trans-5-(4-fluorostyryl)oxazole (trans-10d)
(0.728 g, 92 %) as colorless crystals: mp 73-76 °C; Rf (PE/E=10:1) = 0.65; UV (EtOH) max/nm
(/dm3mol-1cm-1): 274 (10817), 284 (12200); IR max/cm-1: 1645, 1534, 1457, 1361; 1H NMR
(CDCl3, 600 MHz): /ppm 7.85 (s, 1H, H-2), 7.47-7.44 (m, 2H, H-ar), 7.08-7.05 (m, 4H, H-ar,
et, 4), 6.84 (d, Jet = 16.1 Hz, 1H, H-et); 13C NMR (CDCl3, 150 MHz): /ppm 163.1 (d), 161.4
(s), 149.8 (s), 131.9 (s), 128.6 (d), 127.7 (d), 123.5 (d), 115.3 (d), 115.2 (d), 112.2 (d); MS m/z
(EI) = 189 (100, M+); HRMS(Q-TOF) for C11H8FNO: (M+H)+calcd = 190.0590, (M+H)+
=
found
190.0666.
trans−−(−chloro-2-phenylvinyl)oxazole (trans-10e)
(1.01 g, 94 %) as yellow crystals: mp 62.3-62.4 °C; Rf (PE/E=10:1) = 0.14, UV (EtOH) max/nm
(/dm3mol-1cm-1): 225 (7646), 291 (23972), 303 (25341), 318 (15546); IR max/cm-1: 3126,
1443, 974, 829, 633; 1H NMR (CDCl3, 600 MHz): /ppm 7.88 (s, 1H, H-2), 7.75 (d, J9,10 = 7.4
Hz, 2H, H-9), 7.41 (t, J9,10 = J10,11 = 7.4 Hz, 2H, H-10), 7.35 (d, J10,11 = 7.4 Hz, 1H, H-11), 7.31
(s, 1H, H-4), 7.26 (s, 1H, H-7); 13C NMR (CDCl3, 150 MHz): /ppm 150.9 (d, C-2), 149.6 (s),
133.8 (s), 129.7 (d), 128.8 (d), 128.5 (d), 128.4 (s), 125.3 (d), 117.8 (s); HRMS(MALDI-
TOF/TOF) for C11H8ClNO: (M+H)+calcd = 206.0367, (M+H)+found = 206.0374.
Synthesis of 5-(2-vinylphenyl)oxazole (15)
(0.513 g 60 %) as oil: Rf (PE/E = 5:1) = 0.44; UV (EtOH) max/nm (/dm3mol-1cm-1): 265
(14159), 235 (20436); IR max/cm-1: 3128, 1501, 1317, 1103, 914, 639; 1H NMR (CDCl3, 600
MHz): /ppm 7.95 (s, 1H, H-2), 7.63 – 7.61 (m, 1H, H-Ar), 7.58–7.56 (m, 1H, H-Ar), 7.38 –
7.35 (m, 2H, H-Ar), 7.23 (s, 1H, H-4), 7.00 (dd, Ja,c = 17.40 Hz, Jb,c = 10.95 Hz, 1H, H-c), 5.72
(dd, Ja,c = 17.40 Hz, Ja,b = 1.26 Hz, 1H, H-a), 5.39 (dd, Jb,c = 10.95 Hz, Ja,b = 1.26 Hz, 1 Hz, H-
b); 13C NMR (CDCl3, 75 MHz): /ppm 150.60 (d), 150.15 (s), 136.23 (s), 135.39 (d), 128.97
(d), 127.90 (d), 127.50 (d), 127.19 (d), 125.92 (s), 125.34 (d), 117.03 (t); HRMS(MALDI-
TOF/TOF) for C11H9N2O: (M+H)+calcd = 172.0757, (M+H)+found = 172.0760.
Photochemistry of 4-/5-(aryl/heteroarylethnyl)oxazoles
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10.1002/ejoc.201800737
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A quartz vessel was charged with 4/5-styryl/heteroaryl-oxazoles (5-10) (0.0009 mol) in 300 mL
of benzene with addition of small amount of iodine and was irradiated at 300 nm and 350 nmin
Rayonet reactor for 4h, 7h, 11h, 24h. After irradiation the solvent was removed in vacuum and
the residue chromatographed on silica gel column using petroleum ether/diethyl ether (variable
ratio) as eluent.
naphtho[2,1-d]oxazole (12a)[51] (0.140 g, 92 %, lit[51] 14 %) as colorless crystals : mp 50-51
°C; Rf (PE/E=10:2) = 0.43; UV (EtOH) max/nm (/dm3mol-1cm-1): 222 (29823), 233 (31946),
311 (1545), 326 (2098); IR max/cm-1: 3099, 2921, 1498, 1261, 1087, 1066; 1H NMR (CDCl3,
600 MHz): /ppm 8.26 (d, Jar = 8.6 Hz, 1H, H-ar), 8.25 (s, 1H, H-2 ), 8.00 (d, Jar = 8.2 Hz, 1H,
H-ar), 7.86 (d, Jet= 8.7 Hz, 1H, H-et), 7.82 (d, Jet= 8.7 Hz, 1H, H-et), 7.67-7.64 (m, 1H, H-ar),
13
7.59-7.56 (m, 1H, H-ar); C NMR (CDCl3, 150 MHz): /ppm 151.2 (d), 145.6 (s), 136.1 (s),
131.4 (s), 128.1 (d), 126.5 (d), 125.5 (d), 125.0 (d), 120.0 (s), 119.8 (d), 118.4 (d).
Irradiation without the presence of oxygen and iodine
0.154 g (c = 3 × 10-3 mol/L) of 5-(2-vinylphenyl)oxazole (15) in 300 mL of benzene (purged
with argon for 30 min) at 300 nm was irradiated for 76h. After removal of the solvent and
purification 0.025 g (16 %, lit.51 14%) of naphtho[2,1-d]oxazole (12a) was obtained.
°
6-methylnaphtho[2,1-d]oxazole (12b) (0.081 g, 49 %) as yellow crystals: mp 62–64 C; Rf
(PE/E=10:1) = 0.15; UV (EtOH) max/nm (/dm3mol-1cm-1): 238 (24720), 270 (3775), 281
1
(3480), 293 (2296), 314 (1522), 329 (2185); IR max/cm-1: 2972, 1531. 1504, 1379, 1263; H
NMR (CDCl3, 600 MHz) /ppm 8.22 (s, 1H, H-2), 8.13 (d, Jar = 8.2 Hz, 1H, H-10/12), 7.98 (d,
J6,7 = 8.9 Hz, H-6/7), 7.88 (d, J6,7 = 8.9 Hz, 1H, H-6/7), 7.53 (dd, Jar = 8.2 Hz, Jar = 7.0 Hz, 1H,
13
H-11), 7.41 (d, Jar = 7.0 Hz, 1H, H-10/12), 2.77 (s, 3H, CH3); C NMR (CDCl3, 75 MHz)
/ppm 151.7 (d, C-2), 136.3 (s), 135.4 (s), 131.0 (s), 126.9 (d), 126.7 (d, C), 124.5 (s), 121.6
(d), 120.6 (s), 118.5 (d), 118.4 (d), 20.2 (q, CH3); MS m/z (EI): 183 (100, M+); HRMS(MALDI-
TOF/TOF) za C12H9NO: (M+H)+calcd = 184.0757, (M+H)+measured = 184.0756.
naphthho[2,1-d]oxazole-6-carbonitrile (12c) (0.158 g, 90 %) as yellow powder: mp 158-165
0C, Rf (PE/E = 20:1) = 0.19; UV (EtOH) max/nm (/dm3 mol-1 cm-1): 220 (2140), 247 (3150),
253 (3972), 300 (349); IR max/cm-1 (NaCl): 2919, 2228, 1079; 1H NMR (CDCl3, 600 MHz):
δ/ppm 8.53 (d, J2,3 = 7.5 Hz, 1H, H3), 8.31(s, 1H, Hox), 8.25 (d, J4,5=8.5 Hz, 1H, H4/5), 8.09 (d,
J4,5 = 8.6 Hz, 1H, H4/5), 8.00 (d, J1,2= 7.5 Hz, 1H, H1), 7.72 (t, J1,2 = J2,3 = 7.5 Hz, 1H, H2); 13C
NMR (CDCl3, 150 MHz): /ppm 225.6 (s, CN), 152.1 (d), 131.8 (d), 130.3 (s), 129.3 (s), 122.1
(d), 121.4 (d), 121.3 (d), 121.1 (d), 119.9 (s), 117.0 (s), 97.2 (s); MS m/z (EI): 194 (100, M+).
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10.1002/ejoc.201800737
European Journal of Organic Chemistry
2-methyl-naphtho[2,1-d]oxazole-6-carbonitrile (12d) (0.066 g, 35 %) as oil: Rf (PE/E = 20:1)
= 0.12; UV (EtOH) max/nm (/dm3 mol-1 cm-1):303 (3260), 338 (Sh 1784); IR max/cm-1 (NaCl):
3011, 2230, 1109; 1H NMR (CDCl3, 600 MHz): δ/ppm 8.45 (d, Jar = 8.8 Hz, 1H, Har1/3), 8.19
(d, Jar = 9.9 Hz, 1H, Har5/6), 7.98 (d, Jar = 9.9 Hz, 1H, Har5/6), 7.96 (dd, Jar = 7.4 Hz, Jar = 1.1 Hz,
1H, Har1/3), 7.68 (dd, Jar = 8.8 Hz, Jar = 7.4 Hz, 1H, Har2), 2.80 (s, 3H, CH3); 13C NMR (CDCl3,
150 MHz): /ppm 163.7 (s), 146.1 (s), 138.7 (s), 131.3 (d), 129.6 (s), 125.3 (d), 124.6 (d), 121.5
(d), 120.8 (d), 119.6 (s), 117.2 (s), 110.6 (s), 14.13 (q, CH3); MS m/z (EI): 208 (100, M+).
8-metoxynaphto[2,1-d]oxazole (13a) (0.160 g, 90 %) as yellow powder: mp 131-1410C; Rf
(PE/E = 20:1) = 0.43; UV (EtOH) max/nm (/dm3 mol-1 cm-1): 225 (9427), 246 (11694), 280
(1681), 316 (626); 1H NMR (CDCl3, 600 MHz): δ/ppm 8.22 (s, 1H, Hox), 7.88 (d, J2/3 = 8.8 Hz,
1H, H3), 7.73 (d, J4,5 = 8.5 Hz, 1H, H4/5), 7.70 (d, J4,5 = 8.5 Hz, 1H, H4/5), 7.52 (d, J1,2 = 2.5 Hz,
1H, H1), 7.20 (dd, J1,2 = 2.5 Hz, J2,3 = 8.8 Hz, 1H, H2), 4.00 (s, 3H, OCH3); 13C NMR (CDCl3,
13
150 MHz): /ppm C NMR (CDCl3, 150 MHz): /ppm 158.1 (s), 151.1 (s), 136.6 (s), 129.8
(d), 126.7 (s), 124.7 (d), 124.2 (d), 121.0 (s), 117.8 (d), 115.7 (d), 98.6 (d), 55.0 (q); MS m/z
(EI): 200 (100, (M+H)+); HRMS (Q-TOF) for C12H9NO2: (M+H)+calcd = 200.0633, (M+H)+
found
= 200.0705.
8-methylnaphtho[2,1-d]oxazole (13b) (0.107 g, 65 %) as yellow powder: mp 121-129 0C; Rf
(PE/E = 20:1) = 0.45; UV (EtOH) max/nm (/dm3 mol-1 cm-1): 224 (35106), 241 (39824), 280
(4554), 312 (1207), 326 (1694); IR max/cm-1 (NaCl): 3096, 1497, 1261, 1091; 1H NMR (CDCl3,
600 MHz): δ/ppm 8.21 (s, 1H, Hox), 8.01 (brs, 1H, H1), 7.87 (d, J2,3 = 8.4 Hz, 1H, H3), 7.76 (d,
J4,5 = 8.8 Hz, 1H, H4/5), 7.75 (J4,5 = 8.8 Hz, 1H, H4/5), 7.39 (dd, J2,3 = 8.4 Hz, J1,2 = 1.5 Hz, 1H,
H2), 2.59 (s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 151.1 (d, C-ox), 145 2 (s), 136.6
(s), 136.1 (s), 129.7 (s), 127.9 (d, C-3), 127.7 (d, C-2), 124.7 (d, C-4/5), 118.8 (d, C-1), 117.3
(d, C-4/5), 21.4 (CH3); MS m/z (EI): 183 (100, M+); HRMS(Q-TOF) za C12H9NO: (M+H)+
calcd
= 184.0684, (M+H)+found = 184.0755.
8-nitronaphtho[2,1-d]oxazole (13c) (0.165 g, 86 %) as colorless powder: 84-96 0C; Rf (PE/E
= 20:1) = 0.11; UV (EtOH) max/nm (/dm3 mol-1 cm-1):258 (1116), 270 (Sh 928), 300 (511);
IR max/cm-1 (NaCl): 3584, 2913, 1600, 1509, 1344, 1275; 1H NMR (CDCl3, 600 MHz): δ/ppm
9.21 (d, J1,2 = 2.2 Hz, H1), 8.35 (s, 1H, Hox), 8.34 (dd, J1,2 = 2.2 Hz, J2,3 = 8.9 Hz, 1H, H2), 8.14
13
(d, J2/3 = 8.9 Hz, 1H, H3), 8.07 (d, J4,5 = 8.7 Hz, 1H, H4), 7.93 (d, J4,5 = 8.7 Hz, 1H, H5); C
NMR (CDCl3, 150 MHz): /ppm 152.2 (s), 133.7 (s), 129.8 (d), 129.2 (d), 124.8 (d), 122.4 (d),
121.0 (s), 118.9 (d), 118.8 (s), 117.4 (s), 116.7 (d); MS m/z (EI): 214 (100, M+); HRMS (Q-
TOF) for C11H6N2O3: (M+H)+calcd = 215.0378, (M+H)+found = 215.0450.
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10.1002/ejoc.201800737
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2-methyl-8-methoxynaphtho[2,1-d]oxazole (13d) (0.080 g, 45 %) as white powder: 122-125
0C; Rf (PE/E = 20:1) = 0.44; UV (EtOH) max/nm (/dm3 mol-1 cm-1): 227 (28292), 246 (43332),
254 (35544); IR max/cm-1 (NaCl): 2923, 2225, 1450, 1225, 1023; 1H NMR (CDCl3, 600 MHz):
δ/ppm 7.84 (d, J2,3 =8.9 Hz, 1H, H3), 7.66 (d, J4,5 = 8.5 Hz, 1H, H4/5), 7.59 (d, J4,5 = 8.5 Hz, 1H,
H4/5), 7.44 (d, J1,2 = 2.3 Hz, 1H, H1), 7.15 (dd, J1,2 = 2.3 Hz, J2,3 = 8.9 Hz, 1H, H2), 3.98(s, 3H,
OCH3), 2.74(s, 3H, CH3); 13C NMR (CDCl3, 150 MHz): /ppm 162.9 (s), 158.5 (s), 146.2 (s),
138.3 (s), 130.3 (d), 126.7 (s), 124.5 (d), 121.2 (s), 117.8 (d), 115. 7(d), 55.5 (q, OCH3), 14.6
(q, CH3); MS m/z (EI): 213 (100, M+); HRMS (Q-TOF) for C13H11NO2: (M+H)+calcd = 214.0790,
(M+H)+measured = 214.0860.
2-methyl-8-methylnaphtho[2,1-d]oxazole (13e) (0.094 g, 53 %) as yellow powder: mp 71-75
0C; Rf (PE/E = 20:1) = 0.70; UV (EtOH) max/nm (/dm3 mol-1 cm-1):272 (5973); IR max/cm-1
(NaCl): 3110, 1517, 1251; 1H NMR (CDCl3, 600 MHz): δ/ppm 7.95 (d, J1,2 = 0.9 Hz, 1H, H1),
7.84 (d, J2,3 = 7.8 Hz, 1H, H3), 7.69 (Jet = 9.0 Hz, 1H, Het), 7.66 (Jet = 9.0 Hz, 1H, Het), 7.34 (dd,
J1,2 = 0.9 Hz, J2,3 = 7.8 Hz, 1H, H2), 2.73 (s, 3H, CH3), 2.58 (s, 3H, CH3); 13C NMR (CDCl3,
150 MHz): /ppm 162.8 (s), 148.3 (s), 137.9 (s), 136.7 (s), 129.6 (s), 128.4 (d), 127.5 (d), 124.5
(d), 120.4 (s), 118.9 (d), 117.3 (d), 21.8 (q), 14.6 (q); MS m/z (EI): 197 (100, M+); HRMS(Q-
TOF) za C13H11NO: (M+H)+calcd = 198.0841, (M+H)+measured = 198.0911.
2-methyl-8-nitronaphtho[2,1-d]oxazole (13f) (in a mixture with 40% of unknown impurity
with the same Rf value) (0.086, 42%) as yellow powder: 91 - 105 0C; Rf (PE/E = 20:2) = 0.15;
1H NMR (CDCl3, 600 MHz): δ/ppm 9.15 (d, Jar = 2.3 Hz, 1H, H-ar1), 8.32 (d, Jar = 7.6 Hz, 1H,
H-ar2), 8.10 (d, Jar = 9.3 Hz, 1H, H-ar4), 7.97 (d, Jar = 7.6 Hz, 1H, H-ar3), 7.86 (d, Jar = 7.6 Hz,
1H, H-ar5), 2.81 (s, 3H, CH3); MS m/z (EI): 228 (100, M+); HRMS (Q-TOF) for C12H8N2O3:
(M+H)+calcd = 229.0535, (M+H)+measured = 229.0605.
6-methylnaphtho[1,2-d]oxazole (14a) (0.163 g, 99 %) as yellow crystals: mp 107.5–107.8 0C;
Rf (PE/E=10:3) = 0.20; UV (EtOH) max/nm (/dm3mol-1cm-1): 225 (36251), 280 (6150), 290
(5888), 311 (2975), 319 (2529), 325 (4491); IR max/cm-1: 3129, 1531, 1505, 1391, 1241, 1031;
1H NMR (CDCl3, 600 MHz): /ppm 8.40 (d, J10,11 = 8.2 Hz, 1H, H-10), 8.21 (s, 1H, H-2), 8.00
(d, J6,7 = 9.2 Hz, 1H, H-6/7), 7,74 (d, J6/7 = 9.2 Hz, 1H, H-6/7), 7.56 (dd, J10,11= 8.2 Hz, J11,12
=
7.1 Hz, 1H, H-11), 7.40 (d, J11,12= 7.1 Hz, 1H, H-12), 2.77 (s, 3H, CH3); 13C NMR (CDCl3, 75
MHz): /ppm 151.5 (d, C-2), 147.3 (s), 135.9 (s), 135.1 (s), 130.3 (s), 127.1 (d, C-11), 126.9
(s), 126.5 (d, C-12), 122.8 (d, C-6/7), 120.4 (d, C-10), 110.5 (d, C-6/7), 20.1 (q, CH3); MS m/z
(EI): 183 (100, M+), 155 (10%), 126 (9%), 102 (7%); HRMS(Q-TOF) za C12H9NO2:
(M+H)+calcd = 184.0757, (M+H)+measured = 184.0759.
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10.1002/ejoc.201800737
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8-N,N-dimethylamino-naphtho[2,1-d]oxazole (14b) (0.063 g, 33 %) as orange powder: 61-
0
64 C; Rf (PE/E = 20:1) = 0.15; UV (EtOH) max/nm (/dm3mol-1cm-1): 254 (17936), 316
(7040), 350 (4879); IR max/cm-1 (NaCl): 2950, 2300, 1590, 1410, 1266; 1H NMR (CDCl3, 600
MHz): δ/ppm 8.08 (s, 1H, H-2ox), 7.74 (d, Jar = 8.8 Hz, 1H, H-et), 7.60 (d, Jar2,3 = 9.0 Hz, 1H,
H-3), 7.46 (d, Jar1,2 = 2.5 Hz, 1H, H-1), 7.08 (dd, Jar1,2 = 2.5 Hz, Jar2,3 = 9.0 Hz, 1H, H-2), 3.07
13
(s, 6H, 2xCH3); C NMR (CDCl3, 150 MHz): /ppm 150.6 (d, C-2ox), 149.5 (s), 148.2 (s),
129.5 (d), 128.4 (s), 127.8 (s), 126.3 (d), 123.8 (s), 114.7 (d), 106.4 (d), 100.6 (d), 40.7 (q,
2xCH3); MS m/z (EI): 212 (100, M+); HRMS (Q-TOF) for C13H12N2O: (M+H)+calcd = 213.0950,
(M+H)+measured = 213.1024.
0
8-chloronaphtho[2,1-d]oxazole (14c) (0.141 g, 77 %) as white powder: mp 121-125 C; Rf
(PE/E = 20:1) = 0.80; UV (EtOH) max/nm (/dm3mol-1cm-1): 288 (5142), 322 (1850); IR

max/cm-1 (NaCl): 1690, 1620, 1451; 1H NMR (CDCl3, 600 MHz): δ/ppm 8.50 (d, Jar= 2.1 Hz,
H-1), 8.23 (s, 1H, H-ox2), 7.91 (d, Jar= 8.7 Hz, 1H, H-3), 7.81 (d, Jar= 9.0 Hz, 1H, H-et), 7. 81
(d, Jar= 9.0 Hz, 1H, H-et), 7.50 (dd, Jar = 8.7 Hz, Jar = 2.1 Hz, 1H, H-2); 13C NMR (CDCl3, 150
MHz): /ppm 151.8 (d), 148.1 (s), 134.9 (s), 133.5 (s), 130.1 (d), 129.4 (s), 127.4 (s), 126.5 (d),
126.4 (d), 121.4 (d), 111.2 (d); MS m/z (EI): 203 (100, M+); HRMS (Q-TOF) for C11H6ClNO:
(M+H)+calcd = 204.0138, (M+H)+measured = 204.0212.
8-fluoronaphtho[2,1-d]oxazole (14d) (0.050 g, 33 %) as white powder: mp 89-91 0C; Rf (PE/E
1
= 20:1) = 0.82; IR max/cm-1 (NaCl): 1705, 1599, 1561, 1101; H NMR (CDCl3, 600 MHz):
δ/ppm 8.22 (s, 1H, H-2ox), 8.10 (dd, Jar = 2.4 Hz, Jar = 9.4 Hz H-1), 7.96 (dd, Jar = 8.8 Hz, Jar
= 9.4 Hz H-2), 7.82 (d, Jar= 8.8 Hz, 1H, H-et), 7.68 (d, Jar= 8.8 Hz, 1H, H-et), 7.32 (dd, Jar =
8.8 Hz, Jar = 2.4 Hz, 1H, H3); 13C NMR (CDCl3, 150 MHz): /ppm 162.5 (s), 160.9 (s), 151.6
(d), 148.1 (s), 135.4 (s), 127.9 (s), 126.5 (d), 115.5 (d), 110.4 (d), 106.2 (d); MS m/z (EI): 187
(100, M+); HRMS (Q-TOF) for C11H6FNO: (M+H)+
= 188.0433, (M+H)+
=
calcd
measured
188.0501.
Supporting Information
This file contains all of the 1H and 13C spectra along with UV and 2D HETCOR spectra of some
compounds.
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Text for the TOC
Biological activity of naphtho[1,2-d]oxazoles and heterobenz[1,2-d]oxazoles, prompted the
further photochemical synthesis of substituted naphtho[1,2-d/2,1-d]xazoles. Required p- and
o-phenyl-substituted 5-arylethenyloxazoles were prepared by Van Leusen reaction. For the
preparation of the substituted 4-(aryl/heteroarylethenyl)oxazoles the Wittig reaction was
utilized.
Key topic
Oxazole photochemistry
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