Synthesis and photochemical properties of 2,4,6,-triaryl-4h-1,4-oxazines

Article abstract of DOI:10.3987/COM-13-12876

A series of 2,4,6-triaryl-4H-1,4-oxazines was synthesized, and their photochemical properties were studied. The 2,4,6-triaryl-4H-1,4-oxazines underwent photoreaction to N-(1-methoxy-2-oxo-2-arylethyl)-N-arylformamides determined by 1H NMR, 13C NMR, MS, and single crystal X-ray diffraction analyses.

Full text of DOI:10.3987/COM-13-12876

HETEROCYCLES, Vol. 89, No. 2, 2014
359
HETEROCYCLES, Vol. 89, No. 2, 2014, pp. 359 - 373. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 30th October, 2013, Accepted, 6th December, 2013, Published online, 6th January, 2014
DOI: 10.3987/COM-13-12876
SYNTHESIS
AND
PHOTOCHEMICAL
PROPERTIES
OF
2,4,6,-TRIARYL-4H-1,4-OXAZINES
Hongbo Tan, Hongxing Xin, and Hong Yan*
College of Life Science and Bio-engineering, Beijing University of Technology,
Beijing, 100124, P.R. China.*Corresponding author. Tel: (+86) 010-67396642;
E-mail: hongyan@bjut.edu.cn
Abstract – A series of 2,4,6-triaryl-4H-1,4-oxazines was synthesized, and their
photochemical properties were studied. The 2,4,6-triaryl-4H-1,4-oxazines
underwent photoreaction to N-(1-methoxy-2-oxo-2-arylethyl)-N-arylformamides
1
determined by H NMR, 13C NMR, MS, and single crystal X-ray diffraction
analyses.
INTRODUCTION
Heterocycles possess intrinsic reactivity that enables a wide variety of versatile and productive
transformations. Because of their ubiquitous presence in natural products and drugs, the development of
novel and efficient preparations of these structures remains a fundamental goal of organic synthesis.
Although the importance of 1,4-oxazines has been extensively documented, primarily as a result of
pharmaceutical and chromogenic research,1-8 there is only one known synthesis of
2,4,6-triphenyl-4H-1,4-oxazine.9 In connection with our research on the synthesis of heterocycles
containing nitrogen or oxygenand particular interest in six-membered rings,10-12 we intended to prepare a
series of oxazines and broaden the scope of the reported method. A series of the desired
2,4,6-triaryl-4H-1,4-oxazines was synthesized by the reaction of N,N-bis(phenacyl)anilines with an
excess of POCl3 in pyridine (Scheme 1). Because we are interested in the photochemical properties of
heterocycles containing nitrogen or oxygen,13-16 the photochemical properties of the
triaryl-4H-1,4-oxazines were investigated. The 2,4,6-triaryl-4H-1,4-oxazine was unstable and
photoreacted to the N-(1-methoxy-2-oxo-2-arylethyl)-N-arylformamide during UV irradiation in MeOH
(Scheme 2).

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HETEROCYCLES, Vol. 89, No. 2, 2014
R1
R1
R1
R1
O O
N
O
CH2Br
R1
O
N
NH2
Na2CO3
EtOH
POCl3
+
R2
pyridine
R2
R2
R1 = 1: H
R1 = 5: H
2: 4-Me
3: 4-Cl
6: 4-Me
7: 4-Cl
R2 = a: H; b: 4-Me; c: 4-Cl
4: 4-OMe
8: 4-OMe
Scheme 1. Synthesis of 2,4,6-triaryl-4H-1,4-oxazines
R1
R1
R1
O
N
R1
O
N
CHO
R2
hv
+
CO2H
MeO
MeOH
R2
9a: R1 = R2= H
9b: R1 = H, R2 = 4-Me
10a: R1 = 4-Cl, R2 = H
11: R1 = H
12: R1 = 4-Cl
5a, 5b and 7a
Scheme 2. Photoreaction of 2,4,6-triaryl-4H-1,4-oxazines
RESULTS AND DISCUSSION
Synthesis of 2,4,6-triaryl-4H-1,4-oxazines (5-8)
The synthesis of the 2,4,6-triaryl-4H-1,4-oxazines was carried out according to the literature,9 and
2,4,6-triphenyl-4H-1,4-oxazine (5a) was obtained as the only product by the reaction of
N,N-bis(phenacyl)aniline (1a) with an excess of POCl3 in pyridine. When substituents (R1 and R2) were
introduced on the phenyl rings, the breadth of the method was shown by the formation of various
4H-1,4-oxazines (Table 1). The yields of the triaryl-4H-1,4-oxazines varied predictably with the identity
of the substituents (R1 and R2), and the best yields of 7c were obtained when R1 and R2 were both 4-Cl
(74%). For example, when R1 is H, the yield of 5c (R2 = 4-Cl) is higher than that of 5a and 5b. When R2
is H, the yield of 7a (R1 = 4-Cl) was higher than that of 5a or 6a. These results show that an
electron-withdrawing group at R1 and R2 is preferred. It is probably because the electron-withdrawing
group is beneficial for the large conjugated structure and decreases the electronic density throughout.
When R1 is 4-OMe, a trace of 8a-c was observed by TLC during the reaction and disappeared within a

HETEROCYCLES, Vol. 89, No. 2, 2014
361
few minutes. The phenyl rings with strong electron-donating groups (R1 = 4-OMe) may cause the
2,4,6-triaryl-4H-1,4-oxazines to be unstable.
Table 1. The yields of 2,4,6-triaryl-4H-1,4-oxazines (5-8)
Products
R1
R2
Yields[a](%)
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
H
H
50
53
63
53
57
63
60
65
74
-
H
4-Me
4-Cl
H
H
4-Me
4-Me
4-Me
4-Cl
4-Cl
4-Cl
4-OMe
4-OMe
4-OMe
4-Me
4-Cl
H
4-Me
4-Cl
H
4-Me
4-Cl
-
-
[a] Isolated yields.
Photochemical study of 2,4,6-triaryl-4H-1,4-oxazines (5-8)
In this experiment, the 2,4,6-triaryl-4H-1,4-oxazines were found to be stable in the solid state and
unstable in solution. Due to their common features, 5a was chosen as a representative compound to
investigate their stability in a variety of conventional solvents (such as MeOH, benzene, hexane,
dichloromethane, EtOAc, acetone, tetrahydrofuran, acetonitrile, pyridine, and so on). The results showed
that 5a was unstable in solvents, except for MeOH, acetone and pyridine. And 5a was found more soluble
in MeOH than acetone and pyridine. So, MeOH was chosen as the solvent in the study of the
photochemical properties of the title compounds.

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Table 2. The UV-Vis absorption data of 2,4,6-triaryl-4H-1,4-oxazines (5a-c) and (7a-c)
Compounds
5a
5b
5c
7a
7b
7c
236
236
240
244
242
244

max(nm)
346
348
346
354
354
352
436
444
438
454
456
450
20,981
22,941
3,278
41,407
45,519
7,037
51,333
50,481
7,574
21,459
18,152
3,794
27,000
23,389
4,722
29,563
26,169
7,369

max(Lmol-1cm-1)
The UV-Vis absorption spectra of 5 and 7 in MeOH at a concentration of 1×10−5 M are shown in Table 2
and Figure 1. Several absorption peaks were observed in the linear absorption spectra for all of the
molecules in the wavelength ranging from 220 to 600 nm, while almost no linear absorption was
observed beyond 600 nm. The spectral shapes are similar because that these compounds have the same
stem nuclei of the 2,4,6-triaryl-4H-1,4-oxazine structure. The maximum absorptions range from 236 to
242 nm, 346 to 356 nm, and 436 to 456 nm and are similar to the UV-Vis absorption spectra of 5a.9
Figure 1. The UV–Vis absorption spectra of 5 and 7 in MeOH at a concentration of 1×10−5 M

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363
The results in Table 2 and Figure 1 show that the red shifts of the absorption peaks are observed solely
because of the introduction of auxochrome groups on the phenyl ring. For example, when R1 is the same,
the wavelength maximum of 5b (R1 = H, R2 = p-Me) is 444 nm, while the wavelength maximum of 7b
(R1 = p-Cl, R2 = p-Me) is 456 nm, which is 12 nm longer than that of 5b. According to the data above,
obviously that when R1 is auxochrome group, such as -Cl, the UV-Vis absorption spectra of
2,4,6-triaryl-4H-1,4-oxazines show red shifts of the absorption peaks.
The photostability was investigated by the changes of UV-Vis absorption spectra irradiated with UV
lights of 450 W medium pressure mercury lamp in MeOH at a concentration of 10−5 M (Figure2). After
irradiation for 1 h, all three wavelength maxima of 5a and 7a (236-244 nm, 346-354 nm, and 436-454 nm)
decreased dramatically from those taken before the irradiation. In particular, the wavelength maximum at
346-354 nm (the absorbance of the phenyl rings in the 2- and 6-position) decreased in magnitude, and the
436-454 nm peaks (the absorbance of the conjugated ring) disappeared. The changes in the UV-Vis
absorption spectra may be caused by fragmenting the conjugated structures during irradiation.
Figure 2. The UV-Vis absorption spectra of 5a and 7a before (solid lines) and after (dashed lines)
irradiation for 1h in MeOH
To elucidate the photochemical reaction of 2,4,6-triaryl-4H-1,4-oxazines, 5a was used as reactant in a
model reaction in MeOH. 5a was irradiated by a 450 W medium pressure mercury lamp, and the progress

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of the reaction was monitored by TLC. After irradiation for approximately 1 h, 9a and benzoic acid 11
were obtained in the yields of 12% and 10% (Scheme 2). A similar transformation of 5a also occurred by
irradiation with sunlight for about 3 days, and the yields of 9a and 11 were almost the same as those
obtained from irradiation with the mercury lamp. The structure of 9a was
1
N-(1-methoxy-2-oxo-2-phenylethyl)-N-phenylformamide confirmed by H NMR, 13C NMR, and MS.
Due to their structural similarity, compounds 5b and 7a were irradiated under the same conditions used
for 5a in MeOH. The results indicate that the 2,4,6-triaryl-4H-1,4-oxazines undergo a photoreaction to the
N-(1-methoxy-2-oxo-2-arylethyl)-N-arylformamides (9, 10) and corresponding benzoic acids (11, 12).
The substituents on the benzene rings have minor effects on the yields of the photoreaction, e.g., the
yields of 9b and 10a, which have electron-donating and electron-withdrawing groups, respectively, are
similar.
Figure 3. ORTEP diagram of the crystal structure of 10a (drawn at 50% thermal ellipsoids)
The structures of 9a-b, 10a were confirmed by 1H NMR, 13C NMR, and MS. Compound 10a will be used
as a representative example for discussing the details of the structures. In the1H NMR spectra of 10a,
there was a signal from the aldehyde group at δ 8.50, signals corresponding to the 9 protons on the two
benzene rings in the range of δ 6.99-7.76, a signal from the methine group at δ 6.92, a signal from the

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365
methoxy groupat δ 3.67. In the 13C NMR spectra of 10a there were only 12 signals due to the symmetry
of the benzene ring. The two carbonyl carbons resided at δ 190.8 and 163.4 respectively, the 8 signals of
the benzene rings appeared at δ 82.8-140.4, and the 2 signals from the the two saturated carbons were
found at δ 56.6 and 76.7. MS (ESI) m/z (%) = 325.7 [M+Na]+. Single crystal X-ray diffraction of 10a
(Deposition number CCDC-735378) further proves that the photoreaction product is
N-(1-methoxy-2-oxo-2-phenylethyl)-N-phenylformamide (Figure 3).
O
N
O
N
O
N
O
O
hv
hv
MeO
1O2
MeO
MeOH
5a
M1
M2
O
O
O2
CO2H
O
+
MeO
N CHO
MeO
N CHO
MeOH
9a
11
M3
Scheme 3. Supposed mechanism for the formation of 9a
A mechanism of the formation of 9a is speculated via the photoaddition by the MeOH and photooxygen
by the singlet oxygenshown in Scheme 3. The 5a is added by MeOH molecule to give M1 via
anti-Markownikoff addition. Actually, when other alcohols were used in this reaction, 5a could not give
the corresponding photoadditional products. The reaction may proceed via photoinduced electron-transfer
(PET) between photoexcited 5a with some kind of electron acceptor (O2 is possible candidate) to give
radical cation of 5a, then the radical cation of 5a attacks on MeOH, then deprotonation, one-electron
•-
reduction of the resulting radical (maybe from O2 ) to give anion, and protonation, according to
Mizuno.17 The conversion of M1 to M2 is speculated to be associated with the singlet oxygen which
probably comes from air in solution by absorbing UV (wavelengths <320 nm).18-22 It was proved by the
additions of air and N2. The formation of 9a was accelerated with the addition of air and abated under
nitrogen atmosphere. The presence of singlet oxygen was proved by the addition of quencher or
photosensitizer which can capture the singlet oxygen or convert the oxygen molecule to singlet oxygen.

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The quencher was 1,4-diazabicyclo[2.2.2]octane which slowed down the formation of 9a and 11
dramatically. The photosensitizer was a rubrene which speeded up the reaction considerably. The
1,2-dioxetane M2 is the precursor of the C-C bond cleavage product M3 and an intramolecular
electron-transfer mechanism is proposed for the cleavage of these peroxides. The M2 is decomposed by a
stepwise process involving homolysis of the peroxide bond to form a diradical with subsequent C-C bond
cleavage product M3.23 The N-formyl group stabilizes M3 probably because the electron-withdrawing
effect of the formyl prevents the lone-pair electron of the nitrogen from participating in breaking the C-O
bond of M3.24 In Scheme 3, there is another possibility that reverses the order of photoaddition of MeOH
and singlet oxygen. Namely, route of addition of singlet oxygen occurs first, then MeOH photochemically
adds. The accurate and reasonable explanation of the mechanism of the photoreaction of
2,4,6-triaryl-4H-1,4-oxazines will be proposed by the further studies.
EXPERIMENTAL
Materials and Methods
All chemicals were purchased from commercial sources and used without further purification. Thin-layer
chromatography (TLC) was conducted on silica gel 60 F254 plates (Merck KGaA). Melting points were
1
13
determined on a XT-5A digital melting point apparatus and are uncorrected. H NMR spectra and C
NMR spectra were recorded on a Bruker Avance 400 spectrometer at 400 MHz and 100 MHz using
CDCl3 or acetone-d6 as the solvent and tetramethylsilane (TMS) as the internal standard. High-resolution
mass spectral (HRMS) analyses were carried out using a VG 70SE mass spectrometer (Manchester, UK),
which was operated in electron impact or electrospray ionization mode. UV-Vis absorption spectra were
measured using a U-4100 UV/VIS spectrophotometer (Hitachi). Elemental analysis was performed on a
vario EL elemental analyzer. Irradiation for both the photostability studies and photochemical reactions
was conducted using an Osram HBO 450W/2 medium pressure mercury lamp. To mimic UV radiation, a
10-mm-thick Pyrex filter was placedbetween the lamp and the sample that was irradiated. The filter
allows irradiation only by wavelengths greater than 290 nm. The samples were irradiated while in quartz
cuvettes.
General procedure for the synthesis of N,N-bis(phenacyl)anilines
A mixture of phenacyl bromide (12 mmol), Na2CO3 (12 mmol), and aniline (6.0 mmol) was stirred under
reflux at 110 C. The progress of the reaction was monitored by TLC. After the indicated reaction time,
the solid products 1-4 were recrystallized from EtOH.
N,N-Bis(phenacyl)aniline (1a). Yellow needles, yield 65%; mp 196.2-197.4 C (mp 198 C11); 1H NMR

HETEROCYCLES, Vol. 89, No. 2, 2014
367
spectra (400 MHz, CDCl3, 25 C): δ 8.03 (d, J = 7.2 Hz, 4H, Ar-H), 7.62 (t, J = 7.6 Hz, 2H, Ar-H), 7.51
(t, J = 7.6 Hz, 4H, Ar-H), 7.16 (t, J = 7.6 Hz, 2H, Ar-H), 6.73 (t, J = 7.6 Hz, 1H, Ar-H), 6.55 (d, J = 8.4
Hz, 2H, Ar-H), 4.95 (s, 4H, N-CH2).
1
N,N-Bis(phenacyl)-4-toluidine (1b). Yellow needles, yield 73%; mp 153.2-154.1 C (mp 158 C11); H
NMR spectra (400 MHz, CDCl3, 25 C): δ 8.01 (d, J = 7.2 Hz, 4H, Ar-H), 7.61 (t, J = 7.6 Hz, 2H, Ar-H),
7.49 (t, J = 7.6 Hz, 4H, Ar-H), 6.75 (d, J = 8.8 Hz, 2H, Ar-H), 6.57 (d, J = 8.8 Hz, 2H, Ar-H), 4.95 (s,
4H, N-CH2), 2.24 (s, 3H, CH3).
1
N,N-Bis(phenacyl)-4-chloroaniline (1c). Yellow needles, yield 55%; mp 158.3-160.2 C11; H NMR
spectra (400 MHz, CDCl3, 25 C): δ 8.02 (d, J = 7.6 Hz, 4H, Ar-H), 7.67 (t, J = 7.2 Hz, 2H, Ar-H), 7.56
(t, J = 7.6 Hz, 4H, Ar-H), 7.09 (d, J = 8.8 Hz, 2H, Ar-H), 6.50 (d, J = 8.8 Hz, 2H, Ar-H), 5.03 (s, 4H,
N-CH2).
N,N-Bis(4-methylphenacyl)aniline (2a). Yellow needles, yield 62%; mp 103.7-104.5 C (mp 103 C11);
1H NMR spectra (400 MHz, CDCl3, 25 C): δ 7.93 (d, J = 8.0 Hz, 4H, Ar-H), 7.30 (d, J = 8.0 Hz, 4H,
Ar-H), 7.14 (t, J = 7.6 Hz, 2H, Ar-H), 6.73 (d, J = 7.2 Hz, 1H, Ar-H), 6.52 (d, J = 8.4 Hz, 2H, Ar-H),
4.92 (s, 4H, N-CH2), 2.43 (s, 6H, CH3).
N,N-Bis(4-methylphenacyl)-4-toluidine (2b). Yellow needles, yield 70%; mp 142.7-144.3 C (mp
128C11); 1H NMR spectra (400 MHz, CDCl3, 25 C): δ 7.91 (d, J = 8.0 Hz, 4H, Ar-H), 7.29 (d, J = 8.0
Hz, 4H, Ar-H), 6.95 (d, J = 8.0, 2H, Ar-H), 6.47 (d, J = 8.4 Hz, 2H, Ar-H), 4.90 (s, 4H, N-CH2), 2.43 (s,
6H, CH3), 2.20 (s, 3H, CH3).
1
N,N-Bis(4-methylphenacyl)-4-chloroaniline (2c). Yellow needles, yield 54%; mp 178.5-179.3 C11; H
NMR spectra (400 MHz, CDCl3, 25 C): δ 7.90 (d, J = 8.0, 4H, Ar-H), 7.29 (d, J = 8.0 Hz, 4H, Ar-H),
7.08 (d, J = 9.2 Hz, 2H, Ar-H), 6.43 (d, J = 9.2 Hz, 2H, Ar-H), 4.89 (s, 4H, N-CH2), 2.43 (s, 6H, CH3).
N,N-Bis(4-chlorophenacetyl)aniline (3a). Yellow needles, yield 76%; mp 108.1-109.8 C (mp 110
C11); 1H NMR spectra (400 MHz, CDCl3, 25 C): δ 7.96 (d, J = 8.4 Hz, 4H, Ar-H), 7.48 (d, J = 8.4 Hz,
4H, Ar-H), 7.17 (t, J = 8.0 Hz, 2H, Ar-H), 6.76 (t, J = 7.2 Hz, 1H, Ar-H), 6.52 (d, J = 8.0 Hz, 2H, Ar-H),
4.90 (s, 4H, N-CH2).
N,N-Bis(4-chlorophenacyl)-4-toluidine (3b). Yellow needles, yield 80%; mp 137.3-138.1 C (mp 140.0
C11); 1H NMR spectra (400 MHz, CDCl3, 25 C): δ 7.93 (d, J = 7.6 Hz, 4H, Ar-H), 7.33 (d, J = 7.6 Hz,
4H, Ar-H), 6.97 (d, J = 8.4 Hz, 2H, Ar-H), 6.49 (d, J = 8.4 Hz, 2H, Ar-H), 4.88 (s, 4H, N-CH2), 2.23 (s,
3H, CH3).
1
N,N-Bis(4-chlorophenacyl)-4-chloroaniline (3c). Yellow needles, yield 67%; mp 181.5-182.3 C11; H

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NMR spectra (400 MHz, CDCl3, 25 C): δ 7.94 (d, J = 8.4, 4H, Ar-H), 7.49 (d, J = 8.4 Hz, 4H, Ar-H),
7.11 (d, J = 8.4 Hz, 2H, Ar-H), 6.43 (d, J = 8.8 Hz, 2H, Ar-H), 4.87 (s, 4H, N-CH2).
N,N-Bis(4-methoxyphenacyl)aniline (4a). Yellow needles, yield 60%; mp 150.9-151.2 C (mp 152.0
C11); 1H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.01 (d, J = 8.8 Hz, 4H, Ar-H), 7.14 (t, J = 8.0 Hz,
2H, Ar-H), 6.97 (d, J = 8.8 Hz, 4H, Ar-H), 6.71 (t, J = 7.6 Hz, 1H, Ar-H), 6.53 (d, J = 8.4 Hz, 2H, Ar-H),
4.89 (s, 4H, N-CH2), 3.88 (s, 6H, OCH3).
N,N-Bis(4-methoxyphenacyl)-4-toluidine (4b). Yellow needles, yield 66%; mp 169.2-171.1 C (mp
1
170.0 C11); H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.21 (d, J = 8.8 Hz, 4H, Ar-H), 7.96 (d, J =
8.8 Hz, 4H, Ar-H), 6.94 (d, J = 8.0 Hz, 2H, Ar-H), 6.41 (d, J = 8.4 Hz, 2H, Ar-H), 4.80 (s, 4H, N-CH2),
3.90 (s, 6H, OCH3), 2.20 (s, 3H, CH3).
N,N-Bis(4-methoxyphenacyl)-4-chloroaniline (4c). Yellow needles, yield 49%; mp 168.7-169.3 C11;
1H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.06 (d, J = 8.4 Hz, 4H, Ar-H), 7.31 (d, J = 8.4 Hz, 4H,
Ar-H), 7.03 (d, J = 8.4 Hz, 2H, Ar-H), 6.50-6.52 (m, 2H, Ar-H), 4.94 (s, 4H, N-CH2), 3.63 (s, 6H,
OCH3).
General procedure for the synthesis of 2,4,6-triaryl-4H-1,4-oxazines
A mixture of N,N-bis(phenacyl)anilines (5 mmol) and 0.87 mL (9.4 mmol) of POCl3 in 30 mL of pyridine
(dried over CaH2) was heated with occasional swirling at 100 C for 45 min. The deep red solution was
poured onto 50 mL of crushed ice, and the resulting solid was filtered. The crude products were washed
twice with a small amount of MeOH to purify the products.
2,4,6-Triphenyl-4H-1,4-oxazine (5a). Orange red powder, yield 50%; mp 181.6-182.4 C (mp
1
183.0-185.0 C9); H NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.55 (d, J = 6.8 Hz, 4H, Ar-H),
13
7.29-7.43 (m, 10H, Ar-H), 7.03 (t, J = 6.8 Hz, H, Ar-H), 6.94 (s, 2H, N-CH=); C NMR spectra (100
MHz, 25 C, acetone-d6): δ 142.3, 138.7, 132.8, 129.7, 128.4, 127.5, 122.8, 120.9, 113.8, 109.3.
1
2,6-Diphenyl-4-(4-tolyl)-4H-1,4-oxazine (5b). Orange red powder, yield 53%; mp 115.7-117.2 C; H
NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.75 (d, J = 7.6 Hz, 4H, Ar-H), 7.40 (t, J = 7.6 Hz, 4H,
Ar-H), 7.29 (t, J = 7.6 Hz, 2H, Ar-H), 7.18 (d, J = 8.4 Hz, 4H, Ar-H), 6.98 (s, 2H, N-CH=), 2.28 (s, 3H,
13
Ar-CH3); C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.0, 137.8, 132.9, 130.0, 129.9, 128.4,
127.1, 122.6, 113.9, 110.0, 19.7; HRMS(ESI): (m/z) calcd for C23H19NO: 325.1467 [M]+; found
325.1453.
2,6-Diphenyl-4-(4-chlorophenyl)-4H-1,4-oxazine (5c). Orange red powder, yield 63%; mp 98.6-99.5
C; 1H NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.77 (d, J = 7.6 Hz, 4H, Ar-H), 7.29-7.43 (m, 10H,

HETEROCYCLES, Vol. 89, No. 2, 2014
369
Ar-H), 7.03 (s, 2H, N-CH=); 13C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.7, 138.3, 132.6,
129.2, 128.4, 127.5, 124.6, 122.9, 114.9, 109.0; HRMS(ESI): (m/z) calcd for C22H16ClNO: 345.0830
[M]+; found 345.0812.
1
2,6-Bis(4-tolyl)-4-phenyl-4H-1,4-oxazine (6a). Orange red powder, yield 53%; mp 113.5-114.2 C; H
NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.64 (d, J = 7.6 Hz, 4H, Ar-H), 6.92-7.35 (m, 9H, Ar-H),
13
6.91 (s, 2H, N-CH=), 2.35 (s, 6H, Ar-CH3); C NMR spectra (100 MHz, acetone-d6, 25 C): δ 142.0,
138.5, 137.0, 130.1, 129.4, 129.0, 122.8, 120.3, 113.4, 108.6, 20.4; HRMS(ESI): (m/z) calcd for
C24H21NO: 339.1623 [M]+; found 339.1602.
1
2,4,6-Tri(4-tolyl)-4H-1,4-oxazine (6b). Orange red powder, yield 57%; mp 133.6-134.2 C; H NMR
spectra (400 MHz, acetone-d6, 25 C): δ 7.13-7.60 (m, 12H, Ar-H), 6.87 (s, 2H, N-CH=), 2.27 (s, 6H,
13
Ar-CH3), 2.04 (s, 3H, Ar-CH3); C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.0, 137.8, 132.9,
130.0, 129.9, 128.4, 127.1, 122.6, 113.9, 110.0, 19.7; HRMS(ESI): (m/z) calcd for C25H23NO: 353.1736
[M]+; found 353.1702.
2,6-Bis(4-tolyl)-4-(4-chlorophenyl)-4H-1,4-oxazine (6c). Orange red powder, yield 63%; mp 98.6-99.9
1
C; H NMR spectra (400 MHz, acetone-d6, 25 C): δ 6.90-7.47 (m, 12H, Ar-H), 6.44 (s, 2H, N-CH=),
2.38 (s, 6H, Ar-CH3); 13C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.7, 138.5, 129.4, 129.3,
129.1, 124.2, 122.9, 122.7, 114.7, 109.1, 20.2; HRMS(ESI): (m/z) calcd for C24H20ClNO: 373.1140 [M]+;
found 373.1126.
2,6-Bis(4-chlorophenyl)-4-phenyl-4H-1,4-oxazine (7a). Orange red powder, yield 60%; mp 132.5-133.6
C; 1H NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.78 (d, J = 8.0 Hz, 4H, Ar-H), 7.30-7.54 (m, 9H,
13
Ar-H), 7.05 (s, 2H, N-CH=); C NMR spectra (100 M Hz, acetone-d6, 25 C): δ 140.6, 138.8, 132.6,
129.2, 128.4, 127.5, 124.6, 122.9, 114.9, 109.0; HRMS(ESI): (m/z) calcd for C22H15Cl2NO: 379.0531
[M]+; found 379.0516.
2,6-Bis(4-chlorophenyl)-4-(4-tolyl)-4H-1,4-oxazine (7b). Orange red powder, yield 65%; mp
1
153.9-154.7 C; H NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.74 (d, J = 8.8 Hz, 4H, Ar-H),
7.39-7.42 (m, 4H, Ar-H), 7.21 (d, J = 8.4 Hz, 2H, Ar-H), 7.16 (d, J = 8.4 Hz, 4H, Ar-H), 6.97 (s, 2H,
13
N-CH=), 2.29 (s, 3H, Ar-CH3); C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.0, 138.8, 132.3,
130.0, 128.4, 128.3, 127.6, 124.5, 113.8, 110.1, 19.6; HRMS(ESI): (m/z) calcd for C23H17Cl2NO:
393.0687 [M]+; found 393.0689.
1
2,4,6-Tri(4-chlorophenyl-4H-1,4-oxazine (7c). Orange red powder, yield 74%; mp 145.3-146.7 C; H
NMR spectra (400 MHz, acetone-d6, 25 C): δ 7.65 (d, J = 6.8 Hz, 4H, Ar-H), 7.08-7.45 (m, 8H, Ar-H),

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HETEROCYCLES, Vol. 89, No. 2, 2014
6.95 (s, 2H, N-CH=); 13C NMR spectra (100 MHz, acetone-d6, 25 C): δ 140.6, 138.7, 132.5, 129.2, 128.2,
127.5, 124.6, 122.8, 114.7, 109.0; HRMS(ESI): (m/z) calcd for C22H14Cl3NO: 413.0112 [M]+; found
413.0087.
General procedure for the photoreaction of 2,4,6-triaryl-4H-1,4-oxazines
The 2,4,6-triaryl-4H-1,4-oxazines (0.32 mmol) were dissolved in MeOH (200 mL) and poured into the
photolysis unit. Photo-irradiations were performed using a medium pressure mercury lamp (450 W), and
a 10-mm-thick Pyrex filter was placed between the lamp and sample. The reaction was monitored by TLC.
After completion, the solvent was removed under reduced pressure, and the residue was purified by
chromatography on silica gel using a mixed solvent of petroleum ether and EtOAc (20:3 v/v) to provide 9,
10 and the corresponding benzoic acids 11 and 12.
N-(1-Methoxy-2-oxo-2-phenylethyl)-N-phenylformamide (9a). Pale yellow solid, yield 12%; mp
1
127.2-128.7 C; H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.49 (s, 1H, CHO), 6.98-7.80 (m, 10H,
Ar-H), 6.97 (s, 1H, CH), 3.69 (s, 3H, OCH3); 13C NMR spectra (100 MHz, CDCl3, 25 C): δ 191.9, 163.5,
137.0, 134.5, 133.8, 129.3, 128.7, 128.2, 128.1, 126.3, 82.8, 56.6; MS(ESI) m/z (%) = 291.7 [M+Na]+.
Anal. Calcd (%) for C16H15NO3: C 71.36, H 5.61, N 5.20. Found: C 71.35, H 5.58, N 5.22.
N-(1-Methoxy-2-oxo-2-phenylethyl)-N-(4-tolyl)formamide (9b). Pale yellow solid, yield 15%; mp
1
135.5-136.6 C ; H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.47 (s, 1H, CHO), 7.43-7.85 (m, 5H,
Ar-H), 7.06 (d, J = 8.0 Hz, 2H, Ar-H), 6.98 (s, 1H, CH), 6.86 (d, J = 8.0 Hz, 2H, Ar-H), 3.69 (s, 3H,
13
OCH3), 2.31 (s, 3H, CH3); C NMR spectra (100 MHz, CDCl3, 25 C): δ 191.9, 163.5, 138.2, 134.4,
134.3, 133.8, 129.9, 128.7, 128.2, 126.4, 82.7, 56.6, 21.0; MS (ESI) m/z (%) = 306.7 [M+Na]+. Anal.
Calcd (%) for C17H17NO3: C 72.07, H 6.05, N 4.94. Found: C 72.06, H 6.02, N 4.93.
N-(2-(4-Chlorophenyl)-1-methoxy-2-oxoethyl)-N-phenylformamide (10a). Pale yellow solid, yield
12%; mp 145.1-146.3 C; 1H NMR spectra (400 MHz, CDCl3, 25 C): δ 8.50 (s, 1H, CHO), 6.99-7.76 (m,
13
9H, Ar-H), 6.92 (s, 1H, CH), 3.67 (s, 3H, OCH3); C NMR spectra (100 MHz, CDCl3, 25 C): δ 190.8,
163.4, 140.4, 136.8, 132.7,129.6, 129.4, 129.1, 128.3, 126.2, 82.8, 56.6; MS (ESI) m/z (%) = 325.7
[M+Na]+. Anal. Calcd (%) for C16H14ClNO3: C 63.27, H 4.65, N 4.61. Found: C 63.25, H 4.63, N 4.59.
X-Ray diffraction analysis for 10a (Table 3 and Figure 3)
Crystals of 10a suitable for X-ray diffraction analysis were obtained by the slow evaporation of an EtOAc
solution of 10a at room temperature. The single crystal X-ray diffraction measurement was conducted on
a Rigaku Saturn CCD area-detector diffractometer at 113(2) K using graphite monochromated Mo K

HETEROCYCLES, Vol. 89, No. 2, 2014
371
radiation (λ = 0.71070 Å) in the ω and φ scanning mode. An empirical absorption correction was applied
using the ABSCOR program.25 All structures were solved by direct methods using the SHELXS-97
program26 and refined by full matrix least squares on F2 using the SHELXL-97 program.27 All of the
hydrogen atoms were geometrically fixed using the riding model. Details, including the crystal data, data
collection, and structure refinements, are summarized in Table 3. Deposition number CCDC-735378
forcompound
10a.
Free
copies
of
the
data
can
be
obtained
via
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge, CB21EZ, UK; Fax: +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).
Table 3. Crystal data and structure refinement for 10a
Empirical formula
Formula weight
C16H14ClNO3
303.73
Temperature
113(2) K
Wavelength
0.71070 Å
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/n
a = 14.6024(17) Å
b = 6.3424(6) Å
c = 16.361(2) Å
α = 90o
β = 108.336(2)o
γ = 90o
Volume
1438.3(3) Å3
Z
4
Calculated density
Absorption coefficient
F(000)
1.403 Mg m-3
0.275 mm-1
632.0
Crystal size
0.26×0.06×0.04 mm-3
1.63-27.86o
 Range for data collection
Index ranges
-19 ≤ h ≤ 19, -8 ≤ k ≤ 18, -21 ≤ l ≤ 21
17239/3420 [Rint = 0.0386]
3420/0/192
Reflections collected/unique
Data/restraints/parameters
Goodness-of-fit on F2
R indices (all data)
Extinction coefficient
Largest diff. peak and hole
1.121
R1 = 0.0417, wR2 = 0.1071
0.275
0.256 and -0.462 eÅ-3

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HETEROCYCLES, Vol. 89, No. 2, 2014
ACKNOWLEDGMENTS
This work was financially supported by the Key Projects in the National Science & Technology Pillar
Program (No. 2012ZX10001007-008-002) and the Doctoral Fund of Innovation of Beijing University of
Technology.
REFERENCES
1.
2.
3.
P. J. Rybczynski, R. E. Zeck, J. Dudash, D. W. Combs, T. P. Burris, M. Yang, M. C. Osborne, X.
L. Chen, and K. Demarest, J. Med. Chem., 2004, 47, 196.
G. Caliendo, E. Perissutti, V. Santagada, F. Fiorino, B. Severino, D. Cirillo, R. Emmanuele, L.
Lippolis, A. Pinto, and R. Sorrentino, Eur. J. Med. Chem., 2004, 39, 815.
W. Yang, Y. Wang, Z. Ma, R. Golla, T. Stouch, R. Seethala, S. Johnson, R. Zhou, J. Feyen, and J.
K. Dickson, Jr., Bioorg. Med. Chem. Lett., 2004, 14, 2327.
4.
5.
P. L. Gentili, M. Nocchetti, C. Miliani, and G. Favaro, New J. Chem., 2004, 28, 379.
G. Castaldi, P. Allegrini, R. Fusco, L. Longo, and V. Malatesta, J. Chem. Soc., Chem. Commun.,
1991, 18, 1257.
6.
7.
X. Sun, M. Fan, X. Meng, and E. Knobbe, J. Photochem. Photobiol., A, 1997, 102, 213.
P. S. Anderluh, M. Anderluh, J. Ilaš, J. Mravljak, D. M. Sollner, M. S. Dolenc, M. Stegnar, and D.
Kikelj, J. Med. Chem., 2005, 48, 3110.
8.
9.
D. Xu, A. Chiaroni, M. B. Fleury, and M. Largeron, J. Org. Chem., 2006, 71, 6374.
J. Correia, J. Org. Chem., 1973, 38, 3433.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
R. Q. Li and H. Yan, Hecheng Huaxue, 2005, 13, 597.
C. L. Ni, X. H. Song, H. Yan, X. Q. Song, and R. G. Zhong, Ultrason. Sonochem., 2010, 17, 367.
H. Yan, J. Y. He, Z. L. Tan, X. Q. Song, and R. G. Zhong, Inventor Patent CN101492424, 2009.
X. H. Zhu, C. L. Ni, H. Yan, and R. G. Zhong, J. Photopolym. Sci. Technol., 2009, 22, 379.
H. Yan, H. Q. Wang, C. L. Ni, and X. Q. Song, Acta Crystallogr. Sect. E., 2006, 62, 1951.
H. Yan, C. L. Ni, and H. Q. Wang, Inventor Patent CN 101041662, 2007.
J. L. He, Z. L. Tan, and H. Yan, Acta Crystallogr. Sect. E., 2009, 65, 1129.
K. Mizuno, I. Nakanishi, N. Ichinose, and Y. Otsuji, Chem. Lett., 1989, 18, 1095.
X. Zhang, C. S. Foote, and S. I. Khan, J. Org. Chem., 1993, 58, 47.
W. Adam, M. Ahrweiler, K. Peters, and B. Schmiedeskamp, J. Org. Chem., 1994, 59, 2733.
E. L. Clennan, Tetrahedron, 2000, 56, 9151.
E. L. Clennan, Tetrahedron, 2005, 61, 6665.
R. A. Larson and K. A. Marley, Environmental Photochemistry: Springer, 1999. pp. 123-37.
A. P. Schaap, S. D. Gagnon, and K. Zaklika, Tetrahedron Lett., 1982, 23, 2943.

HETEROCYCLES, Vol. 89, No. 2, 2014
373
24.
25.
R. S. Handley, A. J. Stern, and A. P. Schaap, Tetrahedron Lett., 1985, 26, 3183.
G. Sheldrick, SADABS, Program for Empirical Absorption Correction of Area Detector Data,
University of Göttingen, Germany, 1996.
26.
27.
G. Sheldrick, SHELXS-97, Program for Crystal Structure Solution, University of Göttingen:
Göttingen, Germany, 1997.
G. Sheldrick, SHELXL-97, Program for the Refinement of Crystal Structures from Diffraction
Data, University of Göttingen, Göttingen, Germany, 1997.