Photoinduced Intramolecular formal [4 + 2] Cycloaddition of Aryl-Substituted o-Vinylstyryl-2-oxazoles to Form Benzo[f]quinoline Derivatives: Experimental Results and Theoretical Interpretation

Article abstract of DOI:10.1021/acs.joc.5b01504

A new approach to benzo[f]quinoline derivatives has been found by an effective formal [4 + 2] photocycloaddition process from novel aryl-substituted o-vinylstyryl-2-oxazoles. All of the o-vinylstyryl-2-oxazoles were synthesized by a multicomponent Wittig

Full text of DOI:10.1021/acs.joc.5b01504

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Article
Photoinduced intramolecular formal [4+2] cycloaddition of aryl
substituted o-vinylstyryl-2-oxazoles to form benzo[f]quinoline
derivatives: experimental results and theoretical interpretation
Ivana Sagud, Ivana Antol, Zeljko Marinic, and Marija Sindler-Kulyk
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01504 • Publication Date (Web): 04 Sep 2015
Downloaded from http://pubs.acs.org on September 11, 2015
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Photoinduced intramolecular formal [4+2] cycloaddition of aryl substituted o-
vinylstyryl-2-oxazoles to form benzo[f]quinoline derivatives: experimental results and
theoretical interpretation
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a
b*
c
a*
Ivana Šagud, Ivana Antol, Željko Marinić and Marija ŠindlerꢀKulyk
a
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb,
b
Marulićev trg 19, 10000 Zagreb, Croatia, Laboratory for physicalꢀorganic chemistry, Division of Organic Chemistry
c
and Biochemistry, Rudjer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia, NMR Center, Rudjer
Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
marija.sindler@fkit.hr; iantol@emma.irb.hr
Graphical abstract
h
N
N
H+
O
NH
R
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R'
Abstract
A new approach to benzo[f]quinoline derivatives has been found by effective formal [4+2]
photocycloaddition process from novel aryl substituted oꢀvinylstyrylꢀ2ꢀoxazoles. All of the oꢀ
vinylstyrylꢀ2ꢀoxazoles were synthesized by multicomponent Wittig reaction from
diphosphonium salt of
α,α’ꢀoꢀxylenedibromide, formaldehyde and 5ꢀtolylꢀ, 4ꢀphenylꢀ5ꢀ
methylꢀ and 4,5ꢀdiphenyloxazoleꢀ2ꢀcarbaldehydes. TDꢀDFT calculations revealed that the
intramolecular photocyclization in 2ꢀ(2ꢀvinylstyryl)oxazoles to form benzo[f]quinoline
derivatives proceeds on the S PES via stepwise pathway, namely by 10
π
followed by 6
π ring
1
closure. On that path the existence of a S /S conical intersection was indicated. The reactivity
0 1
of the photocyclization steps depends on the substitution pattern at the positions 4 and 5 of the
oxazole ring where the aryl group in position 5 deactivates the reaction.
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Introduction
1
Benzo[f]quinolines (naphtho[2,1ꢀb]pyridines) are the structural isomers of azaphenanthrenes.
2ꢀ5
A number of synthetic pathways to obtain these derivatives has been reported. One of the
very efficient and simple methods is the oxidative photocyclization of 2ꢀstyrylpyridine
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derivatives . Photocyclization reactions of 2ꢀstyrylpyridine isomers
and their annelated
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derivatives
as well as Shiff’s bases
provide a method to benzo[h]ꢀ, benzo[f]ꢀ,
benzo[f](iso)ꢀquinolines and azahelicenes, respectively. Benzoquinoline derivatives are very
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useful compounds with significant biological and pharmacological properties.
The use of
2
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heteroarylphenylethenes in photochemical synthesis of potentially biologically active
heteroaromatic compounds is expanding. Continuing our interest for conjugated
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heteroaromatic systems with furans,
thiophenes,
pyroles, and sydnones, as well as
their photochemical reactions to heteropolycyclic compounds we extended research to
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oxazole derivatives.
We have recently described novel oxidative photocyclization of
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styryl/heteroarylethenylꢀ5ꢀoxazoles (St-5-ox) to naphthooxazoles (Scheme 1).
Scheme 1. Photochemical electrocyclization of styryl/heteroarylethenylꢀ5ꢀoxazoles (St-5-ox)
Moreover, styrylꢀ4ꢀ and 5ꢀoxazoles (VinSt-4/5-ox), bearing a vinyl substituent in the ortho
position, gave in the absence of oxygen diverse fused tetracyclic oxazoline compounds
(Scheme 2) which further spontaneously hydrolyze to benzobicyclo[3.2.1]octenone
2
9
derivatives. The formation of the fused oxazoline products is explained by initial formal
2+2]cycloaddition followed by 1,6ꢀring closure of resonance stabilized intermediate. In
addition, 4ꢀ(2ꢀvinylstyryl)oxazole (VinSt-4-ox) gave minor product 4ꢀ(1,2ꢀ
[
a
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dihydronaphthalenꢀ2ꢀyl)oxazole (Nph-4-ox), formed in an electrocyclization process of the
hexatriene system of the divinylbenzene moiety (Scheme 2).
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Scheme 2. Photochemical reactions of oꢀvinylstyrylꢀ4/5ꢀoxazoles (VinStꢀ4/5ꢀox)
In this work we describe the photochemical transformation of aryloxazole derivatives
substituted with oꢀvinylstyryl group in the position 2 (1aꢀc). Irradiation of aryl substituted 2ꢀ
(2ꢀvinylstyryl)oxazole derivatives resulted in a completely unexpected photochemical
process, formal intramolecular [4+2] cycloaddition. The influence of the aryl substituents at
the oxazole ring to the transformation of these oxazoles to benzo[f]quinoline derivatives was
observed and explained by molecular modeling. The described photochemical reaction
represents a new synthetic approach for the synthesis of benzo[f]quinoline derivatives.
Results and Discussion
Cis/trans isomers of 2ꢀ(oꢀvinylstyryl)oxazole derivatives (1a-c) were synthesized by Wittig
reactions from the diphosphonium salt of
α,α’ꢀoꢀxylenedibromide, formaldehyde and
appropriate oxazoleꢀ2ꢀcarbaldehydes (2a-c) following our established procedure for the
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synthesis of
β
ꢀheteroaryl derivatives of oꢀdivinylbenzene (Scheme 3).
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Scheme 3. Synthesis of 2ꢀ(2ꢀvinylstyryl)oxazoles (1a-c)
All new compounds were obtained in moderate yields (53ꢀ61%) as mixtures of cis/trans
isomers in a ratio 1:4. The isomers were isolated by column chromatography on silica gel and
characterized by spectroscopic methods (see SI 1). The examination of UV spectra shows a
bathochromic shift of absorption maxima of 1a and 1c [at 344 (transꢀ1a), 325 (cisꢀ1a) and
345 (transꢀ1c), 330 (cisꢀ1c) nm] compared to the absorption maximum of 1b [at 328 (transꢀ
1
b), 308 (cisꢀ1b) nm] due to prolonged conjugation by aryl substituent in the position 5 of the
oxazole ring. The excitation gives rise to S states that probably do not undergo efficient
intersystem crossing to populate T states, based on the styrylꢀ5ꢀoxazole. However,
compounds are weakly fluorescent or nonꢀfluorescent because of efficient deactivation of S1
1
3
0
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0
by photochemical transꢀcis isomerization, as reported for similar compounds. Preliminary
irradiation experiments in UV cuvettes indicated transꢀcis isomerization (see SI 1). Longer
irradiations resulted in a decrease of absorption which suggested formation of products with
1
reduced conjugation. The H NMR spectra of the crude reaction mixtures after the irradiation
performed in a Rayonet reactor at λmax 350 nm in petroleum ether, acetonitrile or benzene
showed the highest conversion in benzene which was used as solvent in further preparative
experiments. The irradiation in acetone gave only highꢀmolecular weight materials,
suggesting that the observed products in benzene do not arise via triplet excited state. A series
of experiments were conducted with 5ꢀtolylꢀ2ꢀ(2ꢀvinylstyryl)oxazole (1a) by varying
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concentration of the compound, irradiation time, but none of them resulted in the formation of
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product 3a. H NMR spectra of the photoꢀmixtures after shorter irradiations (2h) indicated the
cisꢀtrans and transꢀcis isomerization, whereas at longer times (6h) decomposition took place.
On the contrary, the derivatives with the phenyl substituent in the position 4 on the oxazole,
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1
b and 1c, gave selectively new oxaꢀbridged derivatives 3b and 3c, respectively in very good
(>72%) to good yields (38%) (Scheme 4).
Scheme 4. Photochemical reaction of 2ꢀ(2ꢀvinylstyryl)oxazoles 1a-c.
The observed photochemical reactivity of 1b and 1c is significantly different compared to our
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previous reports. The possible photoproduct 4, which would be an analogue to Nph-4-ox
(Scheme 2) as a result of 6 electrocyclization process of the oꢀdivinylbenzene moiety, was
π
not detected. Furthermore, anticipated benzobicyclo[2.1.1]hexene photoproduct 5, as a result
of [2+2] cycloaddition which was the main process in 3ꢀfuran substituted 2ꢀ
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vinylstyrylfurans was also not detected.
Photochemical product 3b could not be isolated. During chromatography on silica gel it was
spontaneously transformed to 6b, isolated in 72% yield (Scheme 5). Photoproduct 3c is stable,
so it was isolated in 38% yield. Cleavage of the oxaꢀbridge and transformation to
benzo[f]quinoline 6c was performed by refluxing 3c in slightly acidified ethanol (Scheme 5).
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Scheme 5. Splitting of oxaꢀbridged 3b and 3c.
The structures of photochemical products 3b,c and benzo[f]quinoline derivatives 6b,c were
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determined by UV, IR, and H and C NMR spectroscopy and mass spectrometry methods.
1
In H NMR spectra, compounds 3b and 3c have a characteristic ABX pattern where the
geminal signals of protons H
for 3c. The signals of the protons in 3c are shifted to low field compared to the signals of 3b,
probably due to a desheilding effect of the benzene ring. The signal of proton H is located at
A B
and H are at 2.40 and 2.02 ppm for 3b and 2.76 and 2.54 ppm
X
3.24 and 3.37 ppm, respectively. Dihydroquinoline derivatives 6b and 6c have AB pattern of
the geminal protons signals in the expected range of 3.24 to 3.76 ppm and a new signal of the
NH proton at 2.35 and 2.67 ppm, respectively (See SI 1).
When the irradiation of 1b and 1c was performed under the same conditions, the conversion
of diphenyl derivative 1c to oxaꢀbridged quinoline 3c (38%) was lower than the conversion of
methylphenyl derivative 1b to 3b (>72%). This can be explained by an influence of the aryl
substituent in the position 5 on the oxazole ring in 1c which evidently reduces the efficiency
of the cyloaddition process.
The evidence that the formation of products 3b and 3c proceeds photochemically and not as a
result of intramolecular DielsꢀAlder thermal [4+2] cycloaddition was obtained by refluxing
the starting compounds (cis-1a,b,c) in benzene, toluene and xylene. In all experiments no
thermal reaction was observed and only starting material was isolated.
Irradiation of 1b and 1c in acetone or benzene solutions in aerobic conditions gave only high
molecular weight products, suggesting that photochemical transformations take place from
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singlet excited state. Furthermore, irradiation of similar annelated furan derivatives in the
presence of benzophenone as triplet sensitizer, performed under conditions to ensure the
excitation of the sensitizer, gave no experimental evidence to the mechanism via the triplet
state. It is presumed that the formation of these oxaꢀbridged derivatives (3b, 3c) could
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fluorescence measurements could not give insight into the singlet excited state reactivity of
aꢀ1c due to competitive cisꢀtrans isomerization, we resorted to theoretical calculations
instead. To shed light into the mechanism of this reaction the topology of the ground state S
the first triplet T and the first excited singlet state S potential energy surface (PES) was
probed by DFT calculations. The TDꢀDFT molecular modeling became a valuable tool in
π followed by 6π ring closure on singlet excited state surface. Since
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,
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interpretation of UVꢀVIS spectroscopic data and understanding of photochemical processes.
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However, special attention to selection of proper density functional must be payed. In the
present work TDꢀM06ꢀ2X/6ꢀ311++G(2d,p)//(U)M06/6ꢀ31+G(d) model was used. The
3
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selection of a hybrid metaꢀexchangeꢀcorrelation M06ꢀ2X density functional for calculating
energies was motivated by its good performance in modeling of the DielsꢀAlder reaction of
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,3ꢀbutadiene and ethylene in the ground state as well as its good description of the excited
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states.
The comparison of calculated vertical excitation energies of cisꢀ2ꢀ(2ꢀvinylstyryl)oxazoles 1aꢀ
c with an available experimental values for max of the first absorption band (see SI 2, Table
1
λ
SI5) showed the excellent agreement. Moreover, one can find that the excitation energies of
substituted derivatives in FranckꢀCondon (FC) point were redꢀshifted compared to
unsubstituted 1d. In accordance to the experimental observation, the decrease of vertical
excitation energy was the most pronounced for derivative 1c. Just mentioned facts were taken
as an additional confirmation of good quality of selected theoretical model for description of
the S PES in the present study.
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The concerted synchronous closure of C11ꢀC5 and C10ꢀC2 bonds (Scheme 6a) and biradical
stepwise pathway where one CꢀC bond forms before the other one (Scheme 6b) were found as
more favorable pathways in the S and T states, respectively. A detailed analysis of the
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theoretical results and Cartesian coordinates of all stationary points were given in the
Supporting information 2 (SI 2).
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Scheme 6. Concerted (a) vs. stepwise (b) pathway for 1 to 3 transformation.
ꢀ1
It should be emphasized that energy barriers higher than 25 kcal mol for the DielsꢀAlder
cycloaddition in the ground state hampered the thermal reaction (see SI 2: Figure SI1 and
Table SI1) as was, indeed, found in experiment. The transformation of 2ꢀ(2ꢀ
vinylstyryl)oxazoles (1) to epoxyꢀbridged derivatives on the T
1
PES was energetically more
favorable than corresponding transformation on the S PES. However, possibility that the
0
photo induced cyclization proceeds on the triplet PES could be discarded due to still high
calculated barriers for production of intermediate A. The barriers are in the range between
ꢀ1
1
2.6 and 19.9 kcal mol (see SI 2: Table SI4). Also, there is a disagreement between the
experimental results and calculations. Namely, the lowest energy barrier was calculated for
the derivative a where photo reaction was not observed at all. The energy barrier for
transformation of derivative b, where the reaction proceeded with 70% yield, was 6.6 kcal
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mol higher than in the case a. It is also interesting to note that the stability of biradical
intermediate A in the T state depends on the substitution pattern. Phenyl substitution in the
1
position 4 of oxazole ring stabilizes and tolyl substitution in the position 5 destabilizes the
intermediate A.
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From the discussion above it comes out that the photochemical reactivity mainly depends on
the evolution of the system away from FranckꢀCondon (FC) point on the S PES. Therefore,
1
the topology of the S PES was probed along both concerted and stepwise pathways by single
1
point TDꢀDFT calculations in all stationary points found in the S
stationary points on the S PES were found and fully optimized for derivatives with
substitution pattern a and c. Stepwise reaction path on the S PES is more favorable: the S
0 1
and T states. Also, new
1
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energy is the lowest for A(T ) geometries where C11ꢀC5 bond is formed. The calculations
1
also indicate the existence of S /S conical intersection (CI) on the path for 1 to 3
0
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transformation in a vicinity of A(T ) minimum where efficient relaxation to the ground state is
expected. It should be emphasized that direct downhill approach to the PES part with the
structures with small S
SI5d) derivatives.
1
/S
0
gaps was found for 1b (see Figure 1b) and 1d (see SI 2, Figure
a)
b)
TSa(S
1
)
85.0
85.0
downhill
approach
TS search
S
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optimization
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1a(S ) min
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TSb(T )
S
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3.7
C5-C11 bond distance / Å
C5-C11 bond distance / Å
1 1 1
Figure 1. Comparison of IRC paths on the T PES starting from (a) TSa(T ) and (b) TSb(T )
ꢀ1
structures. The energies (kcal mol ) were calculated at the M06ꢀ2X/6ꢀ311++G(2d,p)//M06/6ꢀ
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31+G(d) level of theory with respect to the ground state 2ꢀ(2ꢀvinylstyryl)oxazole minimum
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0 1
(S ). Relative energies of the ground and the S state along the paths were given as well.
1 0
Due to small S /S gap, which is also an indication that conical intersection exists nearby, the
0
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molecules could switch to the ground state PES where further relaxation could bifurcate in
different directions: toward products and reactants. On the other hand, the reaction is
prevented by trapping the excited molecules in the S minimum (see Figure 1a, fully
1
optimized structure is given in SI 2, Figure SI5) in the case of derivative with substitution
pattern a. Additionally a relaxed scan for a decrease of the C2ꢀC10 distance on the S
was conducted. The TSa(S ) transition structure (see SI 2, Figure SI5) was found and
confirmed by vibrational analysis. The energy barrier of 5.7 kcal mol using M06ꢀ2X/6ꢀ
11++G(2d,p) method for the path in the S excited state of 1a is a consequence of aryl
1
PES
1
ꢀ1
3
1
substitution in position 5 which, similar to what was found in the T
structures with closed C11ꢀC5 bond in the S state. Although the molecule 1c has similar
shape of S excited state PES (See SI 2, Figure SI4) as found in 1a, it undergoes
1
state, destabilizes
1
1
ꢀ1
photochemical transformation due to lower energy barrier (3.4 kcal mol ). However, it is less
reactive than 1b (30% vs. 70% yield) since part of population doesn’t have enough energy to
surmount the barrier. From TDꢀDFT calculations can be concluded that substitution pattern on
the oxazole ring can tune the reactivity of photocyclization in
o
ꢀvinylstyrylꢀ2ꢀoxazoles by
/S CI where C5ꢀ
changing the shape of PES between FranckꢀCondon point and indicated S
1
0
C11 bond is already formed. A final evidence for the existence of the CI indicated by TDꢀ
37
DFT is provided by CASSCF(8,8)/6ꢀ31+G(d) conical intersection search using the smallest
1 0
model system with no substituents attached on oxazole ring, 1d (optimized CId(S /S )
structure is shown in SI 2, Figure SI6).
Conclusion
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In conclusion, we have shown that 2ꢀ(2ꢀvinylstyryl)oxazoles (1b, 1c) afford oxaꢀbridged
quinoline derivatives 3b, 3c as the major products by formal intramolecular photochemical
[
4+2] cycloaddition. The molecular modeling showed that the photocyclization involves
formation of one CꢀC bond between C5 on oxazole ring and C11 from vinyl group on the S
PES followed by decay to the ground state via S /S conical intersection and subsequent
1
10
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1
0
formation of second CꢀC bond between C2 and C11 in the ground state. Both experimental
and theoretical results revealed the high impact of the phenyl substituent at the oxazole ring
on the photocyclization process. The oxaꢀbridged derivatives 3b and 3c can easily be
transformed to quinoline derivatives. Therefore, photochemistry of transformation of 2ꢀ(2ꢀ
vinylstyryl)oxazoles provides a new synthetic approach for the synthesis of benzo[
derivatives.
f]quinoline
Experimental section
General procedures. Reactions which required the use of anhydrous, inert atmosphere
techniques were carried out under an atmosphere of nitrogen. Petroleum ether, bp 40ꢀ60 ºC,
was used. Solvents were purified by distillation. Column chromatography was carried out on
columns with silica gel (Fluka 0.063ꢀ0.2 nm and Fluka 60 Å, technical grade). TLC was
carried out using plates coated with silica gel (0.2 mm, 0.5 mm, 1.0 mm, Kiselgel 60 F254).
4
Organic layers were routinely dried with anhydrous MgSO and evaporated using a rotary
1
13
evaporator. H and C NMR spectra were recorded on a spectrometer at 300 and 600 MHz.
All NMR spectra were measured in CDCl using tetramethylsilane as reference and some in
3
C D . The assignment of the signals is based on 2DꢀCH correlation and 2DꢀHHꢀCOSY
6
6
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 FTIRꢀATR and FTIR. Mass spectra were
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obtained on a GCꢀMS system. Melting points were obtained using a microscope equipped
apparatus and are uncorrected. HRMS analysis were carried out 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 and on a EXTREL FTMS
001 DD. Irradiation experiments of compound solutions were performed in a tightly closed
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2
vessel in a photochemical reactor equipped with the UVA lamps (316ꢀ400 nm). The solvent
was removed on the rotatory evaporator under reduced pressure in a ventilated hood.
Oxazole ring formation
3
8,39
40
Compounds 5ꢀ(4ꢀmethylphenyl)oxazole (7a),
4ꢀphenylꢀ5ꢀmethyloxazole (7b), and 4,5ꢀ
4
0,41
38ꢀ41
diphenyloxazole
(7c) were prepared according to procedures in the literature.
5-(4-methylphenyl)oxazole (7a): 0.27 g (43%) as white crystals: mp = 63.6ꢀ63.8 ºC; Rf
1
(
PE/E = 10:2) = 0.35; H NMR (CDCl
3
, 600 MHz):
δ/ppm 7.89 (s, 1H, Hꢀ2), 7.55 (d,
J
5a,5b
=
1
3
8.07 Hz, 2H, Hꢀ5a), 7.30 ( s, 1H, Hꢀ4 ), 7.24 (d,
J
5a,5b = 8.07 Hz, 2H, Hꢀ5b); C NMR
(CDCl
3
, 150 MHz):
δ/ppm 150.1 (d, Hꢀ2), 138.7 (s), 129.6 (d), 125.1 (s), 124.4 (d), 120.9 (d),
+
2
1.3 (q); MS m/z (%, fragment) (EI): 159 (100%, M ), 130 (31%), 117 (5%), 90 (2%).
1
4
-phenyl-5-methyloxazole (7b): 1.07 g (42%) as oil: R (PE/E = 10:1) = 0.30; H NMR
f
(CDCl
3
, 300 MHz):
δ/ppm 7.80 (s, 1H, Hꢀ2), 7.69 ꢀ7.66 (m, 2H, Hꢀ4a), 7.46ꢀ7.41 (m, 2H, Hꢀ
1
3
4
b), 7.33ꢀ7.30 (m, 1H, Hꢀ4c), 2.55 (s, 3H, CH ); C NMR (CDCl , 75 MHz): δ/ppm 149.0 (d,
3 3
Cꢀ2), 144.1 (s), 134.1 (s), 131.9 (s), 128.6 (d), 127.3 (d), 126.6 (d), 11.7 (q).
1
4
,5-diphenyloxazole (7c): 1.92 g (35%) as colorless powder: H NMR (CDCl , 600 MHz):
3
δ/ppm 7.95 (s, 1H, Hꢀ2), 7.67ꢀ7.66 (m, 2H, Hꢀar), 7.61ꢀ7.60 (m, 2H, Hꢀar), 7.39ꢀ7.33 (m, 6H,
Hꢀar).
Synthesis of carbaldehydes (2aꢀc)
In 20 mL of ether 30 mmol of oxazole (7aꢀc) is dissolved. The mixture is cooled down to ꢀ70
°C (dry ice in acetone) and then 30 mL of nꢀBuLi is added drop wise. The reaction mixture is
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kept under flow of nitrogen over the whole period of the reaction. 2.20 mL of
N,Nꢀ
dimethylformamide dissolved in 10 mL of dry ether is added drop wise and the reaction
mixture is stired for 30 minutes on low temperature and then additional 90 minutes at room
temperature. The reaction is neutralized with 2M HCl (pH = 5ꢀ6) and the product extracted
with dichloromethane, dryed over magnesium sulphate and the solvent evaporated under
reduced pressure. Crude reaction mixture was purified by column chromatography on silica
gel with petroleum ether/ether (0ꢀ10%) as eluent to give carbaldehydes 2aꢀc.
10
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59
60
5
3
1
-(4-methylphenyl)oxazole-2-carbaldehyde (2a)
ꢀ1
.09 g (55%), oil: R (PE/E=10:2) = 0.35; IR νmax/cm : 3028, 1697 (C=O), 1483, 1609, 1485,
f
1
276, 942; H NMR (CDCl
3
, 600 MHz):
δ
/ppm 9.75 (s, 1H, CHO), 7.69 (d, 2H,
J
5a/5b = 8.01
13
Hz. Hꢀ5a), 7.58 (s, 1H, Hꢀ4), 7.29 (d, 2H, J5a/5b = 8,01 Hz, Hꢀ5b), 2.41 (s, 3H, CH ); C
3
NMR (CDCl
3
, 75 MHz):
δ/ppm 176.5 (d, CHO), 157.4 (s), 140,88 (s), 138.7 (s), 129.9 (d),
+
125.5 (d), 123.5 (s), 120.8 (d), 21.5 (q); MS m/z (EI) (%, fragment): 187 (100%, M ), 159
+
(7,5%), 91 (5%) HRMS (MALDIꢀTOF/TOF) for C11
H
9
NO
2
(M+H) calcd 188.0706, found
188.0707
5-methyl-4-phenyloxazole-2-carbaldehyde (2b)
ꢀ1
2.80 g (50%), oil: R (PE:E=10:2) = 0.30; IR νmax/cm : 3058, 2925, 2854, 1702 (CHO), 1530,
f
1
1
492, 1337, 1016, 788; H NMR (CDCl
3
, 600 MHz)
δ/ppm 9.74 (s, 1H, CHO), 7.71ꢀ7.00 (m,
13
2
H, Hꢀ4a), 7.49ꢀ7,46 (m, 2H, Hꢀ 4b), 7.41ꢀ7,38 (m, 1H, Hꢀ4c), 2.67 (s, 3H , CH ); C NMR
3
3
(CDCl , 150 MHz) δ/ppm: 177.2 (d, CHO), 156.3 (s), 148.8 (s), 138.5 (s), 130.8 (s), 128.9 (d,
3
CꢀAr), 128.4 (d, CꢀAr), 127.0 (d, CꢀAr), 12.3 (q, CH ); HRMS (MALDIꢀTOF/TOF) for
+
C
11
H
9
NO
2
(M+H) calcd 188.0706, found 188.0709.
4
2
4
,5-diphenyloxazole-2-carbaldehyde (2c)
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ꢀ
1
1
6.88 g (92%), oil: IR
νmax/cm : 2820, 1688, 1600, 1578, 1520, 1470, 1440, 1370, 1330; H
NMR (CDCl , 600 MHz):
3
δ
/ppm 9.82 (s, 1H, CHO), 7.72ꢀ7.67 (m, 4H, Hꢀar), 7.44ꢀ7.38 (m,
+
6
H, Hꢀar); MS m/z (%, fragment) (EI): 249 (100%, M ), 221 ( 50%), 193 (75%) 165 (36%).
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Synthesis of 2ꢀ(2ꢀvinylstyryl)oxazole (1a-c)
To a stirred solution of diphosphonium salt of α,α’ꢀoꢀxylenedibromide (3 mmol) in absolute
ethanol (100 ml, kept on 3 Å sieves) simultaneously and dropwise was added a solution of
oxazoleꢀ2ꢀcarbaldehyde (2a-c) (3 mmol) in 4 mL of ethanol and half of a solution of sodium
ethoxide (6,6 mmol, 2.2 equiv in 30 mL of ethanol) in strictly anhydrous conditions under
nitrogen. Reaction mixture was left to stir for 1h. Under the stream of dry nitrogen, gaseous
formaldehyde (obtained by decomposition of paraformaldehyde taken in excess, 1.0 g) was
introduced together with the second quantity of sodium ethoxide that was added dropwise.
Reaction mixture was stirred overnight. After removal of the solvent the residue was worked
up with iceꢀwater, and extracted with benzene (4 × 20 mL). Benzene extracts were dried over
anhydrous MgSO
-(4-methylphenyl)-[2-(2-vinylphenyl)ethenyl]oxazole (1a). By column chromatography on
silica gel using petroleum ether/ether (variable ratio) as eluent afforded 0.47 g (55%) of
mixture of cis trans= 1:4 isomers of compound 1a contaminated with small amounts of cisꢀ
4
. Evaporation of solvent under reduced pressure afforded the crude product.
5
/
and transꢀ5ꢀ(4ꢀmethylphenyl)ꢀ[2ꢀ(2ꢀmethylphenyl)ethenyl]oxazole (impurity). The isomers
were purified and separated by repeated column chromatography on silica gel. Cisꢀisomer was
impossible to purify completely.
Cisꢀ5ꢀ(4ꢀmethylphenyl)ꢀ[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (cis-1a with 14% impurity); oil:
3
ꢀ1
ꢀ1
1
R (PE/E=10:3) = 0.30; UV (EtOH) λmax/nm (
ε
/dm mol cm ): 243 (14076), 325 (12191); H
ar = 7.8 Hz, Hꢀar), 7.40ꢀ7.35 (m, 2H, Hꢀar), 7.28 (t,
Jar = 7.3 Hz, Hꢀar), 7.24 (s, 1H, Hꢀ4), 7.13ꢀ7.08 (m, 4H, Hꢀar), 7.05 (d, Jet = 12.2 Hz, 1H, Hꢀ
et), 6.60 (d, et = 12.2 Hz, 1H, Hꢀet), 5.65 (d, a,b = 1.1 Hz 1H, Hꢀa), 5.24 (d,
f
3
NMR (CDCl , 600 MHz): δ/ppm 7.59 (d, J
J
Ja,c = 17.3 Hz, J
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Jb,c = 11.0 Hz, Jb,a = 1.1 Hz 1H, Hꢀb), 2.32 (s, 3H, CH ) 10; C NMR (CDCl , 150 MHz)
3
3
δ
/ppm: 137.9 (s), 135.6 (s), 134.4 (d), 132.7 (d), 129.1 (d), 128.9 (d), 127.6 (d), 126.8 (d),
1
25.9 (d), 124.9 (d), 123.8 (d), 123.5 (d), 117.1 (t), 116.8 (d), 115.5 (d), 115.4 (s), 20.9 (q,
3
CH ).
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Transꢀ5ꢀ(4ꢀmethylphenyl)ꢀ[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (trans-1a); colorless powder:
°
3
ꢀ1
ꢀ1
mp 85ꢀ87 C; R
f
(PE /E = 10:3) = 0.28; UV (EtOH)
λ
max/nm (
ε
/dm mol cm ): 344 (23876),
ꢀ1
1
266 (16718); IR
ν
max/cm : 2920, 2850, 2160, 1625, 1499, 1120, 966, 750, 505; H NMR
3
(CDCl , 600 MHz) δ/ppm: 7.87 (d, 1H, Jet = 16.2 Hz, Hꢀet), 7.61ꢀ7.58 (m, 2H, Hꢀ5a), 7.52ꢀ
7
7
1
.49 (m, 1H, HꢀAr), 7.36 (s, 1H, Hꢀ4), 7.34ꢀ7.31 (m, 2H, HꢀAr), 7.26ꢀ7.24 (m, 2H, Hꢀ5b),
.15 (dd, 1H, Ja,c = 17.4 Hz, Jb,c = 10.9 Hz, Hꢀc), 7.10ꢀ7.09 (m, 1H, HꢀAr), 6.89 (d, 1H, Jet
6.2 Hz, Hꢀet), 5.68 (dd, 1H, a,b = 1.3 Hz, Hꢀa), 5.45 (dd, 1H,
a,b = 1.3 Hz, Hꢀb), 2.40 (s, 3H, CH ); C NMR (CDCl ; 150 MHz) /ppm: 160.3 (s), 150.7
(s), 138.1 (s), 136.8 (s), 134.1 (d), 133.2 (s), 132.7 (d), 129.1 (d), 128.5 (d), 127.5 (d), 126.5
=
J
a,c = 17.4 Hz,
J
Jb,c = 10.9 Hz,
1
3
J
3
3
δ
(d), 125.9 (d), 124.7 (s), 123.7 (d), 123.7 (d), 122.6 (d), 117.1 (t), 115.5 (d), 20.9 (q); HRMS
+
(
MALDIꢀTOF/TOF) for C H NO (M+H) calcd 288.1383, found 288.1383.
20
17
5-methyl-4-phenyl-[2-(2-vinylphenyl)ethenyl]oxazole (1b). Column chromatography on
silica gel using petroleum ether/ether (variable ratio) as eluent afforded 0.456 g (53%) of
mixture of cis trans= 1:4 isomers of compound 1b contaminated with small amounts of cisꢀ
and transꢀ5ꢀmethylꢀ4ꢀphenylꢀ[2ꢀ(2ꢀmethylphenyl)ethenyl]oxazole (impurity). The isomers
/
were purified and separated by repeated column chromatography on silica gel. Cisꢀ and trans
ꢀ
isomers were impossible to purify completely.
cisꢀ4ꢀphenylꢀ5ꢀmethylꢀ[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (cis-1b with 12.5% transꢀ1b), oil:
3
ꢀ1
ꢀ1
1
R
f
(PE/E = 5:1) = 0.40; UV (EtOH)
NMR (CDCl , 600 MHz): /ppm 7.60 (m, 2H, HꢀAr), 7.54 (brd,
(brd, Ar = 7.5 Hz, 1H, HꢀAr), 7.39 (t, Ar = 7.5 Hz, 1H, HꢀAr), 7.33 – 7.23 (m, 3H, HꢀAr),
λ
max/nm (
ε
/dm mol cm ): 251 (15984), 308 (9631); H
3
δ
J
Ar = 7.5 Hz, 1H, HꢀAr), 7.44
J
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6.99 (brd, Jet = 12.5 Hz, 1H, Hꢀet), 6.90 (dd, Ja,c = 17.6 Hz, Jb,c = 11.2 Hz, 1H, Hꢀc), 6.56 (d,
Jet = 12.5 Hz, 1H, Hꢀet), 5.66 (dd, Ja,c = 17.6 Hz, Ja,b = 1.1 Hz, 1H, Hꢀa), 5.27 (dd, Jb,c = 11.2
13
Hz,
J
a,b = 1.1 Hz, Hꢀb) 2.33 (s, 3H, CH
3
); C NMR (CDCl
3
, 150 MHz)
δ/ppm: 157.5 (s),
143.2 (s), 135.8 (s), 135.0 (s), 134.5 (d, Cꢀc), 134.3 (s), 133.9 (d, Cꢀet), 131.7 (s), 129.1 (d, Cꢀ
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
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2
3
4
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0
ar), 128.0 (d, Cꢀar), 127.6 (d), 126.7 (d), 126.4 (d), 126.1 (d), 124.9 (d), 116.4 (d), 115.4 (t),
+
1
1.3 (q); HRMS (MALDIꢀTOF/TOF) for C H NO (M+H) calcd 288.1383, found
20
17
288.1377.
trans-4ꢀphenylꢀ5ꢀmethylꢀ[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (trans-1b with 15% impurity),
3
ꢀ1
ꢀ1
oil: R
IR
MHz)
ar), 7.51ꢀ7.49 (m, 1H, Hꢀar), 7.45ꢀ7.43 (m, 2H, Hꢀar), 7.34ꢀ7.31 (m, 3H, Hꢀar), 7.15 (dd, 1H,
f
(PE/E = 5:1) 0.44; UV (EtOH)
λ
max/nm (
ε
/dm mol cm ): 328 (22303), 253 (23408);
ꢀ1
1
ν
max/cm : 2922, 2359, 2160, 1599, 1495, 1186, 962, 895, 696, 484; H NMR (CDCl
3
, 600
δ
/ppm: 7.79 (d, 1H, Jet = 16.3 Hz, Hꢀet), 7.70ꢀ7.68 (m, 2H, Hꢀar), 7.59ꢀ7.58 (m, 1H, Hꢀ
J
a,c = 17.3 Hz,
J
b,c = 10.0 Hz, Hꢀc), 6.87 (d, 1H,
J
et = 16.3 Hz, Hꢀet), 5.68 (dd, 1H,
J
a,c = 17.3
13
Hz, Ja,b = 1.2 Hz, Hꢀa), 5.43 (dd, 1H, Jc,b = 10.0 Hz, Ja,b = 1.2 Hz, Hꢀb), 2.60 (s ,3H, CH ); C
3
3
NMR (CDCl , 150 MHz) δ/ppm: 143.4 (s), 136.7 (s), 135.7 (s), 134.1 (d), 133.3 (s), 132.2 (d),
131.8 (s), 128.4 (s), 128.1 (d), 127.5 (d), 126.9 (d), 126.4(d), 126.2 (d), 125.8 (d), 116.9 (t),
+
1
1
4
15.2 (d), 30.9 (d), 29.7 (d), 29.2 (t), 11.5 (q); MS m/z (%, fragment) (EI): 187 (100%, M ),
03 (25%).
,5-diphenyl-2[2-(2-vinylphenyl)ethenyl]oxazole (1c). By column chromatography on silica
gel using petroleum ether/ether (variable ratio) as eluent afforded 0.64 g (61%) of mixture of
cis trans= 1:4 isomers of compound 1c. The isomers were separated by repeated column
/
chromatography on silica gel.
Cisꢀ4,5ꢀdiphenylꢀ2[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (cis-1c), oil: R
f
(PE/E = 10:1) = 0.26;
3
ꢀ1
ꢀ1
1
UV (EtOH)
λ
max/nm (
ε
/dm mol cm ): 330 (10630), 279 (18025), 228 (28575); H NMR
(
CDCl , 600 MHz):
3
δ/ppm 7.67 (m, 1H, HꢀAr ), 7.46 ( 1H, HꢀAr), 7.11 (d, 1H, Jet1,et2 = 12.2
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Hz, Hꢀet /et ), 6.92 (dd, 1H, Jc,b = 17.4 Hz, Jc,a = 11.0 Hz, Hꢀc), 6.65 (d, 1H, Jet1,et2 = 12.2 Hz,
1
2
Hꢀet1/et2), 5.67 (dd, 1H, Ja,c = 17.4 Hz, Ja,b = 1.1 Hz, 1H, Hꢀa), 5.26 (dd, 1H, Jb,c = 11.0 Hz,
13
J
b,a = 1.1 Hz, 1H, Hꢀb); C NMR (CDCl
3
, 600 MHz):
δ/ppm 158.8 (s), 145.2 (s), 136.3 (s),
135.1 (s), 135.6 (d), 135.3 (s), 134.8 (d), 132.5 (s), 129.3 (d), 128.5 (s), 128.3 (d), 128.2 (d),
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128.1 (d), 128.1 (d), 127.9 (d), 127.3 (d), 126.8 (d), 125.9 (d), 125.4 (d), 117.2 (d), 116.0 (t).
ꢀ
HRMS (MALDIꢀTOF/TOF) for C H NO (Mꢀe) calcd 349.146115, found 349.149054.
25
19
Transꢀ4,5ꢀdiphenylꢀ2[2ꢀ(2ꢀvinylphenyl)ethenyl]oxazole (trans-1c); yellow powder: mp
°
3
ꢀ1
ꢀ1
1
06.5ꢀ107 C; R (PE/E = 10:1) = 0.24; UV (EtOH) λmax/nm (
ε
/ dm mol cm ): 345 (21234),
f
ꢀ1
280 (19127), 234 (20621); IR
ν
max/cm (KBr): 1620, 1590, 1525, 1495, 1465, 1435, 1175,
, 600 MHz): /ppm 7.91 (d, et = 16.1 Hz, 1H,
c,a = 17.4 Hz, c,b = 11.0
a,c = 17.4 Hz, a,b = 0.9 Hz, 1H, Hꢀa
, 600 MHz): /ppm 8.08 (d,
1
1
150, 1060, 1015, 960, 910; H NMR (CDCl
3
δ
J
Hꢀet), 7.68 (m, HꢀAr), 7.61 ( m, HꢀAr), 7.51 (m, HꢀAr), 7.15 (dd,
J
J
Hz, 1H, Hꢀc), 6.94 (d,
, 5.44 ( dd,
J
et = 16.1 Hz, 1H, Hꢀet), 5.69 (dd,
J
J
1
)
Jb,c = 11.0 Hz,
J
a,b = 0.9 Hz, 1H, Hꢀb); H NMR (C
6
D
6
δ
Jet = 16.2 Hz, 1H, Hꢀet), 7.92 (m, 2H, HꢀAr), 7.62 (m, 2H, HꢀAr), 7.33 (m, 2H, HꢀAr), 6.93
d, et = 16.2 Hz, 1H, Hꢀet), 5.46 (dd, a,c = 17.2 Hz, 1H, Hꢀa ), 5.11 ( dd,
1.4 Hz, Jb,c = 11.0 Hz, 1H, Hꢀb); C NMR (CDCl , 150 MHz): /ppm 160.1 (s), 145.3 (s),
(
J
J
a,b = 1.4 Hz,
J
a,b
J =
13
δ
3
137.3 (s), 137.0 (s), 134.6 (d), 133.8 (d), 133.7 (s), 132.5 (s), 129.1 (d), 128.9 (s), 128.7 (d),
128.7 (d), 128.6 (d), 128.3 (d), 128.1 (d), 127.0 (d), 126.7 (d), 126.5 (d), 117.6 (t), 115.9 (d);
+
MS, m/z (M , %): 349 (40), 348 (58), 221 (88), 193 (75), 165 (100), 77 (89).
Irradiation experiments
Irradiation of 5-(4-methylphenyl)-2-[2-(2-vinylphenyl)ethenyl]oxazole (1a).
ꢀ3
In a vessel 0.086 g (4.5 × 10 mol/L) a mixture of cisꢀ and transꢀ1a dissolved in benzene was
purged for 20 minutes with argon in a Rayonet reactor at 350 nm with varying irradiation
1
times. After removal of the solvent, H NMR spectra show at shorter irradiation times (≈ 30
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minutes) only trans
ꢀ
cis isomerization and at longer period of irradiation (≈ 9h) only tarry
material.
Irradiation of 5-methyl-4-phenyl-2-[2-(2-vinylphenyl)ethenyl]oxazole (1b). In a vessel
ꢀ3
0
.060 g (3 × 10 mol/L) a mixture of cisꢀ and transꢀ1b dissolved in benzene and purged with
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argon for 20 minutes was irradiated at 350 nm for 5h. After removal of the solvent the crude
1
product based on H NMR contains only 3b (See Supporting Information 1).
1
,10 4,9
12ꢀmethylꢀ13ꢀphenylꢀ15ꢀoxaꢀ14ꢀazatetracyclo[10.2.1.0 .0 ]pentadecaꢀ2,4,6,8,13ꢀpentaene
1
(
3b): H NMR (CDCl
3
, 600 MHz):
Ar = 7.5 Hz, 1H, HꢀAr), 6.90 (d,
A,X = 8.7 Hz, B,X = 4.5 Hz, 1H, HꢀX), 2,40 (dd,
δ
/ppm 7.75ꢀ7.73 (m, 2H, HꢀAr), 7.49ꢀ7.21 (m, 8H, HꢀAr),
E,F = 9.8 Hz, 1H, HꢀE/F), 6.52 (d,
A,B = 11.7 Hz,
7
.15 (d,
J
J
JE,F = 9.8 Hz,
1H, HꢀE/F), 3.24 (dd,
J
J
J
A,X
J =
13
8.7 Hz, 1H, HꢀA), 2.02 (dd, JB,X = 4.5 Hz, JA,B = 11.7 Hz, 1H, HꢀB), 1.88 (s, 3H, CH ); C
3
NMR (CDCl
3
, 150 MHz)
δ/ppm:142.6 (s), 137.1 (s), 133.8 (d), 131.3 (s), 131.0(d), 130.5 (s),
130.3 (d), 128.2 (d), 128.0 (d), 127.6 (d), 127.5 (d), 126.9 (d), 122.3 (d), 98.3 (s), 84.6 (s),
+
42.4 (d), 37.5 (t), 16.8 (q, CH
88.1388, found 288.1378.
3
); HRMS (MALDIꢀTOF/TOF) for C20
H
17NO (M+H) calcd
2
When the crude product was purified by column chromatography on silica gel 0.43 g (72%)
of 6b was isolated.
2ꢀmethylꢀ3ꢀphenylꢀ1
H
,4
) = 0.28; UV (EtOH)
14360), 218 (20098); IR
CDCl 600 MHz):
H
ꢀbenzo[
f]quinoline (6b): colorless powder: mp 58ꢀ61
°C; Rf
3
ꢀ1
ꢀ1
(
(
(
CH
2
Cl
2
λ
max/nm (
ε
/dm mol cm ): 333 (5054), 273 (15836), 251
ꢀ1
1
ν
max/cm : 3400 (NH), 3055, 2930, 1650, 1444, 1137; H NMR
δ
/ppm 8.03ꢀ8.00 (m, 3H, HꢀAr), 7.88 (d, JAr = 8.4 Hz, 1H, HꢀAr), 7.81 (d,
E,F = 8.5 Hz, 1H, HꢀE/F), 7.69 (d, E,F = 8.5 Hz, 1H, HꢀE/F), 7.57ꢀ7.54 (m, 1H, Hꢀ5c), 7.49ꢀ
.46 ( m, 4H, HꢀAr), 3.45 (d, JA,B = 16.4 Hz, 1H, HꢀA/B), 3.31 (d, JA,B = 16.4 Hz, 1H, Hꢀ
3
J
J
7
13
3 3
A/B), 2.09 (brs, 1H, NH), 1.54 (s, 3H, CH ); C NMR (CDCl , 150 MHz) δ/ppm: 172.7 (s),
140.2 (s), 136.0 (s), 132.4 (s), 130.8 (s), 129.5 (d), 128.3 (d), 128.2 (d), 127.7 (d), 127.3 (d),
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126.0 (d), 126.0 (d), 125.2 (d), 123.0 (d), 120.9 (s), 70.8 (s), 37.4 (t), 24.9 (q); MS m/z (%,
+
ꢀ
fragment) (EI): 270 (100%, (M+H) ); HRMS (MALDIꢀTOF/TOF) for C H N (MꢀH) calcd
2
0
17
270.1288, found 270.1284.
Irradiaton of 4,5-diphenyl-2[2-(2-vinylphenyl)ethenyl]oxazole (1c)
.
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ꢀ
3
In a vessel 0.079 g (2.27 × 10 mol/L) a mixture of cisꢀ and transꢀ1c dissolved in benzene
and purged with argon for 20 minutes was irradiated at 350 nm for 6.5 h. After removal of the
solvent crude product was purified by column chromatography on silica gel using
dichloromethane as eluent and gave 0.029 g (37.5%) of 12,13ꢀdiphenylꢀ15ꢀoxaꢀ14ꢀ
1
,10 4,9
azatetracyclo[10.2.1.0 .0 ]pentadecaꢀ2,4,6,8,13ꢀpentaene (3c) as colorless powder: mp
3
ꢀ1
ꢀ1
198ꢀ199
°
C; R
f
(CH
2
Cl
2
) = 0.37; UV (EtOH)
λ
max/nm (
ε
/dm mol cm ): 259 (19414), 335
ꢀ1
1
(1889); IR
ν
max/cm : 2924, 1610, 1447, 1159, 1005, 696, 608; H NMR (CDCl
3
, 600 MHz):
δ
/ppm 7.55ꢀ7.53 ( m, 2H, HꢀAr), 7.44ꢀ7.42 ( m, 2H, HꢀAr), 7.37ꢀ7.33 ( m, 2H, HꢀAr), 7.24ꢀ
E,F = 9.8 Hz, 1H, HꢀE/F), 6.64 (d, E,F = 9.8 Hz, 1H, HꢀE/F),
A,X = 4.3 Hz, 1H, HꢀX ), 2.76 (dd B,X = 8.6 Hz, A,B = 11.4 Hz, 1H,
, 600 MHz) /ppm:
.52ꢀ7.50 ( m, 2H, HꢀAr), 7.30ꢀ7.28 ( m, 2H, HꢀAr), 6.90ꢀ6.89 ( m, 4H, HꢀAr), 6.86ꢀ6.83 (m,
1H, HꢀAr) 6.80ꢀ6.76( m, 2H, HꢀAr), 6.68 (d, E/F = 9.6 Hz, 1H, HꢀE/F), 6.47 (d,
A,X = 4.8 Hz, 1H, HꢀX ), 2.12 (dd
7.19 (m, 2H, HꢀAr), 6.92 (d,
.37 (dd,
HꢀA/B), 2.54 (dd,
J
J
3
J
B,X = 8.6 Hz,
J
J
J
1
J
A,B = 11.4,
J
A,X = 4.3 Hz, 1H, HꢀA/B); H NMR (C
6
D
6
δ
7
J
J
E,F = 9.6 Hz,
1H, HꢀE/F), 3.12 (dd,
J
B,X = 8.4 Hz,
J
J
A/B,X = 4.8 Hz,
J
A,B
=
13
1
1.3 Hz, 1H, HꢀA), 2.08 (dd, JA,B = 11.4, JA/B,X = 8.4 Hz, 1H, HꢀB); C NMR (CDCl , 150
3
MHz)
δ/ppm: 176.5(s), 169.6 (s), 136.9 (s), 135.6 (s), 130.6 (s), 98.9 (s), 88.5 (s), 134.1 (d, Cꢀ
E/F), 130.4 (d), 128.4 (d), 128.2 (d), 128.1 (d), 128.0 (d), 127.9 (d), 127.7 (d), 127.5 (d),
1
26.2 (d), 122.1 (d, CꢀE/F), 42.4 (d, CꢀX), 34.4 (t, CꢀA,B); ); MS m/z (%, fragment) (EI): 349
+
(
100%, M ), 321 (20%), 247 (32%), 167 (65%); HRMS (MALDIꢀTOF/TOF) for C25
H19NO
+
(
M+H) calcd 350.1539, found 350.1524.
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Ring opening of the oxa-bridged derivate 3c
.
The photoproduct 3c (0.015 g) is refluxed in
acidic ethanol (two drops of HCl p.a. in 10 mL of ethanol) for 1h. After cooling the mixture is
neutralized with NaOH, extracted with ether, dried over anhydrous magnesium sulphate,
filtered and the solvent is removed under reduced pressure. The crude product is purified by
column chromatography on silica gel with dichloromethane as eluent and 0.011 g (74%) of 6c
0
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is gained. 2,3ꢀDiphenylꢀ1
H,4Hꢀbenzo[f]quinoline (6c): colorless powder mp 104ꢀ106 °C; R
f
3
ꢀ1
ꢀ1
(
CH Cl ) = 0.40; UV (EtOH)
2
2
λ
max/nm (
ε
/dm mol cm ): 273 (2876), 283 (2750), 338 (1198);
ꢀ1
1
IR νmax/cm : 3379, 3059, 1447, 1215, 908, 698; H NMR (CDCl , 600 MHz)
δ
/ppm: 7.86 (d,
E/F = 8.58, HꢀE/F),
.66 (m, 2H, HꢀAr), 7.48ꢀ7.33 (m, 7H, HꢀAr), 7.25ꢀ7.19 (m, 3H), 3.77 (d, 1H, A,B = 16.7 Hz,
A,B = 16.7 Hz, HꢀA/B), 2.65 (s, 1H, NH); C NMR (CDCl , 150 MHz)
3
1
H, JAr = 8.4 Hz, HꢀHꢀAr ), 7.81 (d, 2H, JE/F = 8.58, HꢀE/F ), 7.77 (d, 1H, J
7
J
13
HꢀA/B), 3.63 (d, 1H,
J
3
δ
1
1
3
/ppm: 169.1 (s), 142.0 (s), 140.4 (s), 136.4 (s), 132.6 (s), 130.6 (s), 129.5 (d), 128.3 (d),
28.1 (d), 127.9 (d), 127.9 (d), 127.4 (d), 126.0 (d), 125.9 (d), 125.2 (d), 124.5 (d), 123.0 (d),
ꢀ
19.8 (s), 74.0 (s), 39.3 (t, A,B); HRMS (MALDIꢀTOF/TOF) for C H N (Mꢀe) calcd
2
5
19
33.1508, found 333.1512.
Computational Details
A key step in preparation of novel benzo[f]quinoline derivatives – transformation of 2ꢀ(2ꢀ
vinylstyryl)oxazoles (1) to epoxy derivatives (3) was rationalized by DFT calculations using
35
M06 density functional. The restricted method was used for all closed shell species while we
employed the unrestricted method for the open shell species. The stationary structures in the
singlet ground state and the lowest triplet state were optimized by using 6ꢀ31+G(d) basis set.
The nature of stationary points was investigated by a full vibrational analysis at the same
theoretical level used for geometry optimization. Harmonic frequencies were used to compute
zeroꢀpoint energies. The total energies were further recalculated using M06ꢀ2X density
functional and larger 6ꢀ311++G(2d,p) basis set. Also, TDꢀDFT approach was used for the
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single point calculation of the first excited singlet state energies in all stationary points found
on the S and T PESs as well as for the search of stationary points in the S excited state. All
0
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43
calculations were carried out using the Gaussian09 suite of programs on the Isabella cluster
(Isabella.srce.hr) at the University of Zagreb Computing Center (SRCE) and visualized by the
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VEGAꢀZZ and Molden programs.
Acknowledgements
This work was supported by grants from the Ministry of Science, Education and Sports of the
Republic of Croatia (grant no. 125ꢀ0982933ꢀ2926 and 098ꢀ0982929ꢀ2917). The authors are
thankful to Dr. N. Basarić for his comments and very useful discussions.
Supporting Information
1
13
Spectral data ( H NMR, C NMR, IR and UV) of synthesized compounds 1ꢀ7 are given in
the Supporting Information 1 (SI 1). Detailed description of computational methods and
analysis of the theoretical results are given in the Supporting Information 2 (SI 2). This
material is available free of charge via the Internet at http://pubs.acs.org.
References
1. Eicher, T.; Hauptmann, S.; Speicher, A.; The Chemistry of Heterocycles: Structures,
Reactions, Synthesis, and Applications 3rd Ed.; WileyꢀVCH Verlag & Co., Weinheim, 2012.
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3
4
. Maiti, G.; Karmakar, R.; Kayal, U. Tetrahedron Lett. 2013, 54, 2920ꢀ2923.
. Wang, X.ꢀS.; Zhou, J.; Yang, K.; Yao, C.ꢀS. Tetrahedron Lett. 2010, 51, 5721ꢀ5723.
. Wang, X.ꢀS.; Li, Q.; Yao, C.ꢀS.; Tu, S.ꢀJ. Eur. J. Org. Chem. 2008, 20, 3513ꢀ3518.
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. Kumler, P. L.; Dybas, R. A. J. Org. Chem. 1970, 35, 125ꢀ131.
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7. Kumler, P. L.; Dybas, R. A. J. Org. Chem. 1970, 42, 3825ꢀ3831.
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2011, 80, 1115ꢀ1133.
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Mele, A.; Sora, I. N.; Pazeri, W. Tetrahedron 2006, 62, 139ꢀ148.
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Meinardi, F.; Mele, A.; Panzeri, W.; Recupero, F.; Sironi, A.; Tubino, R. Eur. J. Org.Chem.
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005, 7, 1247ꢀ1257.
4. Loader, C. E.; Timmons, C. J. J. Chem. Soc. (C) 1966, 1078ꢀ1081.
5. Collin, P. J.; Shannon, J. S.; Silberman, H.; Sternhell,S.; Sugowdz,G. Tetrahedron 1968,
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