A new regioselective synthesis and ambient light photochemistry of quinazolin-1-oxides

Article abstract of DOI:10.1016/j.tet.2007.02.004

Quinazolin-1-oxides were prepared by the oxidation of tetrahydroquinazolines with H₂O₂-tungstate and their ambient light photochemistry was investigated. Substituent effects on their photochemical cyclization and the reactions of the products 1aH-[1,2]oxazireno[2,3-a]quinazolines under photochemical and thermal conditions are reported. The cyclization of quinazolin-1-oxides and the reactions of 1aH-[1,2]oxazireno[2,3-a]quinazolines show pronounced solvent isotope and solvent effects.

Full text of DOI:10.1016/j.tet.2007.02.004

Tetrahedron 63 (2007) 2966–2972
A new regioselective synthesis and ambient light
photochemistry of quinazolin-1-oxides
*
Necdet Coxskun and Meliha C¸ etin
Department of Chemistry, Uludagꢀ University, 16059 Bursa, Turkey
Received 9 September 2006; revised 4 January 2007; accepted 1 February 2007
Available online 4 February 2007
Abstract—Quinazolin-1-oxides were prepared by the oxidation of tetrahydroquinazolines with H2O2–tungstate and their ambient light
photochemistry was investigated. Substituent effects on their photochemical cyclization and the reactions of the products 1aH-
[1,2]oxazireno[2,3-a]quinazolines under photochemical and thermal conditions are reported. The cyclization of quinazolin-1-oxides and
the reactions of 1aH-[1,2]oxazireno[2,3-a]quinazolines show pronounced solvent isotope and solvent effects.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
reaction of compound 1 with different aldehydes in metha-
nol at room temperature, with H2O2–tungstate to give the
corresponding quinazolin-1-oxides 2 (see Scheme 1 and
Table 1 for the yields and mps). In the cases of 2a–d, initially
formed quinazolin-1-oles precipitated and gradually con-
verted to the corresponding products within 25 h. In these
cases, shorter reaction times were achieved by evaporating
the initial reaction solvent (methanol) and subsequently
suspending the residue in chloroform and stirring at room
temperature in the presence of H2O2 and tetrabutylammo-
nium hydrogen sulfate (TBAHS).
The quinazoline ring system is a frequently encountered
moiety in organic syntheses as well as in medicinal chemis-
try.1 Many alkaloids possess a quinazoline skeleton.2 Quin-
azolines are an important class of compounds, which exhibit
anticonvulsant, antibacterial, antidiabetic, and anticancer
activities.1a,3 The chemistry of parent quinazoline and the
synthesis of different quinazoline derivatives are well estab-
lished and a number of methods to prepare quinazolines are
known.4–6
Herein we report the oxidation of in situ formed 2-
substituted-1,2,3,4-tetrahydroquinazolines to quinazolin-1-
oxides7 2 and the photochemical cyclization of the latter
compounds. The substituent effects on the reactions of 1aH-
[1,2]oxazireno[2,3-a]quinazolines 4 under photochemical
and thermal conditions are also reported. The cyclization
of quinazolin-1-oxides 2 and the reactions of 1aH-[1,2]-
oxazireno[2,3-a]quinazolines 4 show pronounced solvent
isotope and solvent effects.
Despite the precautions to avoid direct exposure to light, the
deoxygenated compounds 3 were detected in the crude reac-
tion mixtures by H NMR and in some cases isolated. The
1
yields of the by products 3 were higher in the cases of phenyl
rings having electron-withdrawing groups. The column
chromatography of the reaction mixtures of 2 in 5 mmol
scale afforded indazole in 7–28% yields in all cases. Ind-
azole is assumed to be a product of oxidative intramolecular
coupling of amine 1, which formed from the hydrolysis of
the corresponding tetrahydroquinazoline. The oxidation of
pure 1 in methanol under the conditions of the reaction in
Scheme 1 confirmed this assumption.
2. Results and discussions
2.1. Oxidation of 2-substituted-1,2,3,4-tetrahydro-
quinazolines to quinazolin-1-oxides 2
The singlet for C-4 hydrogen in the 1H NMR spectra of qui-
nazolines 3 in CDCl3 appears at ca. 9.50 ppm, however, the
same proton in compounds 2 appears at ca. 9.0 ppm (see
Table 4 for the characteristic C-4H chemical shifts). The
shift to higher field by ca. 0.5 ppm is ascribed to the positive
resonance effect of the oxygen at N-1. The C-4 hydrogen in
2-chloromethylquinazolin-3-oxides was reported to appear
at 9.50 ppm in DMSO-d6.9 The same shift to higher field
is also observed for C-4. Detailed inspection and comparison
of the 1H NMR spectra of 2a and its deoxygenation product
3a allow further distinction between 1- and 3-oxide. In the
As a continuation of our previous work8 we have treated in
situ formed tetrahydroquinazolines, obtained from the
Keywords: N-Oxides; Quinazoline; Quinazolin-1-ol; Quinazolin-1-oxide;
Quinazolin-3-oxide; Quinazolin-4(3H)-one; Ambient light photochemistry;
Rearrangement; Photochemical deoxygenation; Solvent effect; Solvent
isotope effect.
* Corresponding author. E-mail: coskun@uludag.edu.tr
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.02.004

N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
2967
hν
N
N
2(S1)
3
+
5
+
6
N
O
R
N
R
O
4 (S0)
+hν
2 (S0)
2.H2O2-WO42-
-hν
CH2Cl2
NH
N
N
or CDCl3
+
N
4(S1)
R
N
R
N
H
up to 81%
N
R
5
O
N
O
H
indazole
CHCl3,THF
or Toluene
tetrahydroquinazolines
6
[ox]
1.RCHO
MeOH; rt
82%
N
R
N
3
NH2
NH2
1
Scheme 1. The synthesis of compounds 2–6: (a) R¼Ph; (b) R¼2-furyl; (c) R¼4-MeOC6H4; (d) R¼4-ClC6H4; (e) R¼2-NO2C6H4; (f) R¼3-NO2C6H4; (g)
R¼3,4-(MeO)2C6H3; (h) R¼ethyl.
Table 1. Synthesis of Quinazolin-1-oxides 2
was monitored (see Table 2). It was not surprising that the
decrease in the concentration of 4 was equal to the sum of
the increase in the corresponding 2, 3, 5, and 6. This un-
doubtedly proves that thermal deoxygenation and rearrange-
ments of 4 could produce the starting material 2, the
quinazolines 3, and the rearrangement products 5 and 6.
The comparison of the total conversions (TC) of 2 within
100 min (see Table 2) shows that the order of reactivity in
the photochemical cyclization of compounds 2 is a substitu-
ent dependent process and is as follows: 3,4-(MeO)2C6H3>
4-MeOC6H4>Ph>ethyl>2-furyl>4-ClC6H4>2-NO2C6H4.
This order of reactivity could be rationalized by assuming
that the excited state of the 1-oxides 2(S1) is stabilized by
electron-withdrawing substituents while in the case of
electron-donating groups the latter prefer to cyclize to the
corresponding oxaziridines 4.
Entry Yield (%) RT (h) Mp (ꢀC) Entry Yield (%) RT (h) Mp (ꢀC)
2a
2b
2c
2d
40a (40)b 25
38 (36) 25
41 (38) 25
28 (36) 25
100–101 2e
154–155 2f
151–152 2g
140–141 2h
50c
44
60
65
16
16
16
203–204
227–228
152–153
75–76
2.5
a
Isolated 2-phenyl-1,2,3,4-tetrahydroquinazolin-1-ol was treated with
H2O2–tungstate in the presence of TBAHS in chloroform for 1 h at
room temperature to give the corresponding 2a in 80% yield.
Compounds 2a–d were prepared in a shorter reaction time, when the resi-
due, after evaporation of the methanol, was dissolved in chloroform and
treated with the oxidant system in the presence of phase transfer catalyst.
The yields in the parentheses are according to this method.
The yields of the isolated by-product quinazolines are 7% for 3a, 17% for
3d, and 19% for 3f.
b
c
1H NMR spectrum of 3a, the proton at C-8 and the ortho pro-
tons of the phenyl at C-2 resonate at 8.10 (1H) and 8.60 ppm
(2H), respectively. However, the same protons for 2a are at
8.72–8.74 (C-8 and an ortho proton) and the other ortho pro-
ton is at 8.79 ppm. It is clear that the oxygen is affecting both
the mentioned protons at C-8 and the C-2 phenyl’s ortho pro-
tons, confirming that it is at the N-1 position of the quinazo-
line system. Additional evidence for the structure 2 and its
isomer 3-oxide could be deduced from their mass spectra.
The fragment ion, which is derived from the molecular ion
by loss of HCNO is characteristic for the 3-oxide. The
same fragmentation pattern is absent in the mass spectra of
the 1-oxides.
Comparison of the underlined TC values shows that 4 with
electron-rich aromatic rings are more reactive than those
with electron-poor ones at thermal conditions. The order
of reactivity is: 3,4-(MeO)2C6H3>2-furyl>4-MeOC6H4>
ethyl>Ph>4-ClC6H4.
The rearrangement of 4 to 5 and 6 predominates over their
deoxygenations to 3 under both photochemical and thermal
conditions, however, it is much more pronounced under the
thermal conditions except in the case of 4-methoxyphenyl
substituted 4. It is not clear to define a general rule for the
substituent effects on the R/D value, however, generally
we can say that under both conditions electron-rich substit-
uents favor the rearrangements to 5 and 6.
2.2. Ambient light photochemistry of quinazoline
oxides 2
2.2.1. Substituent effects on the cyclization of quinazolin-
1-oxides 2 and the reactions of 1aH-[1,2]oxazireno[2,3-
a]quinazolines 4. A 0.014 M CDCl3 solution of a series of
1-oxides 2 was exposed to ambient light in Pyrex NMR tubes
for 100 min and the product distribution (see Scheme 1) was
determined by 1H NMR (see Table 4 for the protons charac-
teristic of the compounds determined quantitatively using
the integral areas). After exposure, the samples were kept
in dark for 50 min and the change in the product distribution
Comparison of the 4/R ratios reveals that quinazolines 2 with
electron-donating substituents easily form oxaziridines,
which with the same ease rearrange to compounds 5 and 6.
The electron-withdrawing substituents at C-2 neither pre-
vent the oxaziridine formation nor support their rearrange-
ment. Compound 2e having a 2-nitrophenyl group did not
undergo any photochemical reaction probably due to the
high stabilizing effect of the nitro group on the exited singlet
state of 2e. 4/R ratios imply the stabilizing order for the

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N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
Table 2. Effect of substituents on the product distribution in the photochemical reactions of quinazolin-1-oxides 2 and the rearrangements of 1aH-[1,2]-
oxazireno[2,3-a]quinazolines 4 in CDCl3
Entry
Product distribution (%)
TC (%)
R/Dd
5/6
4/R
2
3
4
5
6
2
4
hna
Db
hn
D
hn
6.08
D
2a
2b
2c
2d
2e
2g
2h
13
2
3 (1)
24
30 (6)
2
4 (2)
3
4 (1)
0
0
16
16
18
22 (4)
73
55
18
0
44
20
51
45
0
8
4
9 (5)
20
25 (5)
36
51 (15)
2
4 (2)
0
0
42.5
45 (2.5)
15
87
6
2
4a
4b
4c
4d
4e
4g
4h
19 (6)c
34
34
14 (6)
4
11 (7)
15
16 (1)
1
2 (1)
0
0
34
36 (2)
7
8 (1)
25e
11
2
1.2
1.4
0.07
0.5
1.63
1.5
1.5
2
66
97
57
0
1
25.5
1
0.2
0.42
0.5
0
0.75
0.86
100
55
12
0
3
9 (6)
43
45 (2)
100
100
0.5
3 (2.5)
18
24 (6)
8
17
3
0
0
7
0
0
99.5
82
4.8
0.8
0.5
0.09
1.91
100
40
N
0.8
0.2
42
25
1.22
21 (6)
1.75
2.42
a
The ambient light exposure time was 100 min. The average light intensity was 150 lux.
The reaction time for the thermal rearrangements was 50 min in the dark at 20 ꢀC.
The values in the brackets are the yields of the products from the thermal reactions of the 1aH-[1,2]oxazireno[2,3-a]quinazolines 4.
b
c
d
e
R/D is the rearrangement/deoxygenation ratio, TC¼total conversion, and 4/R is the ratio of the yields of the oxaziridine 4 to the sum of the yields of 5 and 6.
The ratio of the sum of the yields of all 4 transformation products to the yield of initial 4 multiplied by 100.
oxygen
species
substituents at C-8a of oxaziridines 4 in the excited state
to be: 4-ClC6H4>Ph>ethyl>4-MeOC6H4>2-furyl>3,4-
(MeO)2C6H3. It could be deduced from the 4/R ratios that
thermal rearrangements of 4 to 5 and 6 (see Table 2) are
favored by electron-donating substituents at C-8a.
OH
NH
O
N
O
H2O
3
N
R
-NH3
NH
A
B
H2N
R
7
R
O
The formation of compounds 5 and 6 under photochemical
conditions may result exclusively from the rearrangements
of the excited states of oxaziridine 4, exclusively from the re-
arrangements of ground state 4 or may involve both ways. If
only the thermal rearrangement of 4(S0) was the source of 5
and 6 then their ratios should be close to the ratios under the
thermal reaction conditions where we assume that the only
rearranging product is 4(S0). This is true only in the case of
4-chlorophenyl substituted 4d. In the other cases there are
changes in the ratios of 5 and 6 under photochemical and
thermal conditions. Under photochemical conditions, the
shift to oxygen predominates in the case of aromatic rings
having substituents with a positive resonance effect. The
heteroaromatic electron-rich 2-furyl ring also accelerates
the 2-aryloxyquinazoline formation (see Table 2). The
reverse is true for the unsubstituted phenyl where the pre-
dominating shift is to nitrogen. 3-Nitro-substituted phenyl
does not support at all any rearrangement to 5 and 6; the
only rearrangement is to the starting 2.
Scheme 2. Probable formation pathway for compounds 7.
the yields of cyclization in CHCl3 and CDCl3 reveal that
the reaction is faster in the deuterated solvent. An inverse
solvent isotope effect is observed with the formation of 4a.
The deoxygenation products 3 predominate in CHCl3, while
the rearrangement processes predominate in CDCl3.
The illumination of 2a in THF chemoselectively gave com-
pound 3a. The rate of cyclization in CCl4 was of the same
magnitude as in CDCl3, THF, and CH2Cl2. The deoxygen-
ation predominates in toluene and CCl4, while rearrange-
ment is the main process in CH2Cl2 (Table 3).
2.2.3. Structural elucidation of the rearrangement prod-
ucts of oxaziridines 4. We were able to record, probably for
the first time, the 1H NMR spectrum of the fused oxaziridine
Table 3. Solvent isotope and solvent effects on the photochemical reactions
of 2a
It is highly possible that the oxygen formed under photo-
chemical conditions could be different from the type formed
under thermal conditions. Products isolated from the reac-
tion mixtures of 2b and 2h in THF were proven to be N-
(2-formylphenyl)furan-2-carboxamide 7b and N-(2-formyl-
phenyl)propionamide 7h by spectral means. The formation
of these compounds may be rationalized by the addition of
oxygen species to the main product 3 of the reaction, the
transformations of which could give dihydroquinazolines
A (see Scheme 2). The hydrolysis of their ring-opened
tautomer B could produce compounds 7.
a
b
Solvent
%
%
2
4
D
R
2
4
D
R
CHCl3
CDCl3
THF
CH2Cl2
CCl4
Toluene
92
16
8
16
5
0
58
0
0
27
0
8
0
17
44
2
0
0
0
15
0
29
0
0
18
0
43
21
82
27
52
70
8c
48
0e
73
30
15
9
82
18
30
58
0d
66
38
18
24
a
The product distribution after 100 min exposure.
The product distribution after 200 min exposure.
Also compound 7 with 5% integral area.
A new product having singlet at 9.45 ppm with 9.8% integral area.
Beside the previous at 9.45 ppm (7%) a singlet corresponding to the
carboxamide 7 (11%). D is the yield of 3a and R is the total yield of the
rearrangement products 5a and 6a.
b
c
d
e
2.2.2. Solvent isotope and solvent effects on the cycliza-
tion of quinazoline 1-oxides 2 and the reactions of 1aH-
[1,2]oxazireno[2,3-a]quinazolines 4. The comparisons of

N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
2969
Some characteristic
4a (76% pure), obtained from the ambient light irradiation of
168.2; 9.26
HMBC correlations
H
compound 2a. The spectrum was elicited from the total spec-
trum and is as follows: (CDCl3, 400 MHz) d 7.42–7.50 (3H,
m), 7.52–7.66 (4H, m), 7.85–7.88 (2H, m), 8.72 (1H, s).10
The singlet at 8.72 ppm is assigned to the C-4 proton and is
shifted to higher field in comparison with the values for the
same protons in the aromatic derivatives 2, 3, 5, and 6. These
protons range from 8.52 ppm for the ethyl-substituted oxazir-
idines 4h to 8.79 ppm for the 3-nitrophenyl-substituted ox-
aziridine 4f (see Table 4). Attempts to record the 13C NMR
spectrum failed as the compound gradually converted, in
the dark, to the products shown in Table 2. The photoiso-
merization of 2-methylquinazolin-1-oxide was reported to
give benzooxadiazepines, where the intermediate oxaziri-
dine formation is assumed.12 Compound 5a, contaminated
with 11% of carboxamide 7a, was characterized as a repre-
sentative of the 1-substituted quinazolin-2(1H)-ones. The
presence of a carbonyl peak at 1670 cmꢁ1 in its IR spectrum
is in accordance with the proposed quinazolone structure
(Fig. 1). The 13C NMR spectrum of quinazolone contains
12 peaks. The HSQC spectrum revealed that eight carbons
are CH and four are quaternary. Some of the characteristic as-
signments are shown in Figure 1. The most characteristic
peaks are the singlet at 9.26 ppm, which correlates with the
carbon at 168.2 ppm, assigned to the C4 proton, together
with the doublet at 6.69 ppm, J¼8.8 Hz, which was assigned
to the C-8 proton. The latter proton was shown to belong to
a spin system consisting of four protons by TOCSY1D exper-
iment. All other quinazolones in the investigated reaction
mixtures have the same signals with nearly the same chemi-
116.6
N
N
155.5
N
O
N
O
136.8
115.4; 6.69
144.3
Figure 1. Characteristic NMR data for compound 5a.
127.3; 7.90
164.0; 9.30
122.4
129.5; 7.47
Some characteristic
HMBC correlations
121.7; 7.29
H
N
127.2; 7.90
N
N
O
O
N
H
125.8; 7.52
162.3
135.0; 7.82
153.3
152.0
125.2; 7.26
Figure 2. Some assignments for compound 6a based on 1D and 2D exper-
iments.
3. Conclusions
A convenient regioselective method for the oxidation of
2-substituted-1,2,3,4-tetrahydroquinazolines with H2O2–
tungstate to quinazolin-1-oxides 2 has been developed. An
excellent method, namely ambient light, proved to be effi-
cient for the deoxygenation and the rearrangements of qui-
nazolin-1-oxides 2, if the appropriate solvent is chosen.
The effect of substituents on the cyclization of compounds
2 as well as on the photochemical and thermal reactions of
compounds 4 was investigated in detail. The intermediates
of cyclization of a heterocyclic N-oxide were detected and
1
cal shifts. Table 4 summarizes the H NMR chemical shift
values for the characteristic C-4 proton of the compounds,
which were used in the quantification of the product distribu-
tion of the investigated reactions.
1
Compound 6awas isolated and characterized as the represen-
tative of the second rearrangement product series. The struc-
ture was deduced from the spectral data, some of which are
shown in Figure 2. There is no carbonyl stretch in the IR spec-
trum of the compound. Beside the peaks arising from the
stretching of the aromatic parts of the molecule, there are
strong peaks at 1199 and 1281 cmꢁ1 due to the diaryl ether’s
C–O–C stretching vibrations. These peaks are not so pro-
nounced in the spectrum of 5a. The compound has a charac-
teristic singlet at 9.30 ppm, which corresponds to C-4 proton
as all other 2-aryloxyquinazolines have. The same proton of
the 2-ethoxyquinazoline resonates at 9.12 ppm (see Table 4).
in some cases their H NMR spectra were recorded. For
the first time, these reactions were shown to display solvent
isotope and solvent effects. Structural elucidation of repre-
sentative deoxygenation and rearrangement products of ox-
aziridines 4 (e.g., 3a–g; 5a and 6a) was achieved by 1D and
2D NMR spectral methods. On the other hand, compounds 7
can be regarded as products from the reactions of 3 with the
reactive oxygen species from the deoxygenations of 4.
4. Experimental
4.1. General
The mass spectra of compounds 5a and 6a are nearly the
same. The molecular ion (M+) peaks are the base peaks in
the spectra. The (M+ꢁ1) peaks are the second most intense
peaks.
All ambient light photochemical transformations of quin-
azolin-1-oxides were performed in Pyrex NMR tubes of
the same quality in the same location in the laboratory.
Table 4. C-4H chemical shifts values of compounds 2, 3a–h, 4–6a–h
Entry
2
3
4
5
6
Entry
2
3
4
5
6
a
b
c
9.01
9.03
8.97
8.98
9.48
9.39
9.42
9.46
8.72a
8.63
8.69
8.70
9.26b
9.21
9.23
9.24
9.30b
9.31
9.27
9.29
e
f
g
h
9.03
9.04
8.90
8.82
9.52
9.42
9.35
8.79
8.70
8.52
9.24
9.22
9.28
9.12
d
See Section 2 for the full 1H NMR spectrum of compound 4a.
The compounds’ full characterization data are available in Section 4.
a
b

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N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
The samples were illuminated only by the light coming from
the laboratory windows. The light intensity was measured
with a Pasco high-sensitivity photometer Model OS-8020
(Pasco Scientific, Roseville, CA, USA). The solvents and re-
agents used in the synthesis and photochemical reactions of
quinazolines were Aldrich or Merck quality and were used
without additional purification. Melting points were taken
on an Electrothermal Digital melting point apparatus. Infra-
red spectra were recorded on a Mattson 1000 FTIR. 1H and
13C NMR as well as 2D NMR experiments such as COSY,
HMQC, HMBC, and NOESY 1D were performed on aVarian
Mercury Plus 400 MHz spectrometer. The mass spectra were
recorded on a Fisons VG Platform II instrument. Elemental
analyses were performed on a EuroEA 3000 CHNS analyzer.
119.4, 124.4, 124.9, 127.2, 128.9, 132.3, 134.6, 144.8,
146.5, 149.8, 161.7. Anal. Calcd for C15H12N2O2 (252.27),
MS m/z 252 (M+): C, 71.42; H, 4.79; N, 11.10. Found: C,
71.31; H, 4.75; N, 10.80.
4.2.1.4. 2-(4-Chlorophenyl)quinazolin-1-oxide 2d.
Light orange crystals. 1H NMR (400 MHz, CDCl3):
d 7.49–7.52 (2H, m), 7.75–7.90 (1H, m), 7.98–8.04 (2H,
m), 8.75–8.81 (3H, m), 8.98 (1H, s). 13C NMR (100 MHz,
CDCl3): d 119.5, 124.8, 125.5, 127.3, 128.3, 129.6, 130.7,
131.7, 134.8, 136.9, 144.7, 146.4. Anal. Calcd for
C14H9ClN2O (256.69), MS m/z 256 (M+): C, 65.51; H,
3.53; N, 10.91. Found C, 65.62; H, 3.60; N, 10.80.
4.2.1.5. 2-(2-Nitrophenyl)quinazolin-1-oxide 2e. Yel-
low crystals. 1H NMR (400 MHz, CDCl3): d 7.67–7.71
(1H, m), 7.79–7.84 (3H, m), 7.98–8.03 (1H, m), 8.08 (1H,
d, J¼8.0 Hz), 8.17 (1H, d, J¼7.6 Hz), 8.67 (1H, dd,
J¼8.0, 0.8 Hz), 9.03 (1H, s). 13C NMR (100 MHz,
CDCl3): d 119.5, 124.0, 125.6, 127.4, 128.0, 130.1, 130.8,
132.2, 133.4, 134.9, 143.7, 146.4, 148.9, 149.6. Anal. Calcd
for C14H9N3O3 (267.24), MS m/z 267 (M+): C, 62.92; H,
3.39; N, 15.72. Found C, 63.08; H, 3.43; N, 15.68.
4.2. Synthesis of 2-substituted-quinazolin-1-oxides
4.2.1. One-pot procedure for the oxidation of 2-substi-
tuted-1,2,3,4-tetrahydroquinazolines to quinazolin-
1-oxides 2a–h. General procedure: to a solution of
2-aminobenzylamine 1 (5 mmol, 0.610 g) in MeOH (20 mL),
aldehyde (5 mmol) was added and the reaction mixture
stirred for 1 h at room temperature. H2O2 (20 mmol, 30%,
2.266 g) and Na2WO4$2H2O (0.25 mmol, 0.082 g) were
added and the mixture was stirred for a specified time. The
precipitated 2e from the reaction of 1 with 2-nitrobenzalde-
hyde was isolated by filtration. In the case of 2f the product
precipitated together with the corresponding 2-(3-nitrophe-
nyl)quinazoline 3f, which was purified by preparative
TLC. In the other cases, the solvent was evaporated, water
was added (15 mL), the mixture was basified with 10%
NaOH, and then extracted with chloroform (3ꢂ15 mL).
The extracts were combined and dried over anhydrous
Na2SO4, filtered, and the solvent was evaporated. The resi-
due was subjected to flash column chromatography using sil-
ica gel as an adsorbent and ethyl acetate–petroleum ether
(1:9) as eluent mixture. The isolated products were crystal-
lized from hexane or petroleum ether.
4.2.1.6. 2-(3-Nitrophenyl)quinazolin-1-oxide 2f. Yel-
low crystals. H NMR (400 MHz, CDCl3): d 7.73 (1H, t,
1
J¼7.6 Hz), 7.84 (1H, t, J¼7.2 Hz), 8.04–8.09 (2H, m),
8.38 (1H, dt, J¼8.4, 1.2 Hz), 8.79 (1H, d, J¼9.2 Hz), 9.04
(1H, s), 9.24 (1H, dd, J¼8.0, 1.2 Hz), 9.70 (1H, s). 13C
NMR (100 MHz, CDCl3): d 119.8, 125.4, 125.5, 125.6,
127.6, 129.3, 130.3, 134.2, 135.2, 136.0, 145.1, 146.5,
147.9, 148.4. Anal. Calcd for C14H9N3O3 (267.24), MS
m/z 267 (M+): C, 62.92; H, 3.39; N, 15.72. Found C,
62.85; H, 3.40; N, 15.60.
4.2.1.7. 2-(3,4-Dimethoxyphenyl)quinazolin-1-oxide
2g. Light orange crystals. 1H NMR (400 MHz, CDCl3):
d 3.91 (3H, s), 3.95 (3H, s), 6.95 (1H, d, J¼9.1 Hz), 7.65
(1H, t, J¼7.4 Hz), 7.92 (2H, m), 8.49–8.56 (2H, m), 8.68
(1H, d, J¼8.6 Hz), 8.90 (1H, s). 13C NMR (100 MHz,
CDCl3): d 56.4, 56.4, 110.7, 113.6, 119.7, 124.8, 125.0,
125.5, 127.6, 129.4, 135.0, 145.3, 146.8, 148.5, 150.0, 151.8.
Anal. Calcd for C16H14N2O3 (282.29), MS m/z 282 (M+): C,
68.07; H, 5.00; N, 9.92. Found: C, 67.58; H, 4.9; N, 9.76.
4.2.1.1. 2-Phenylquinazolin-1-oxide 2a. Tan colored
crystals. H NMR (400 MHz, CDCl3): d 7.53–7.57 (3H,
1
m), 7.75–7.79 (1H, m), 7.99–8.04 (2H, m), 8.71–8.73 (2H,
m), 8.79 (1H, dd, J¼8.8, 0.8 Hz), 9.01 (1H, s). 13C NMR
(100 MHz, CDCl3): d 119.6, 124.8, 127.2, 128.1, 129.4,
130.2, 130.3, 130.9, 132.4, 134.6, 144.8, 146.2. Anal. Calcd
for C14H10N2O (222.24), MS m/z 222 (M+): C, 75.66; H,
4.54; N, 12.60. Found: C, 76.12; H, 4.60; N, 12.65.
4.2.1.8. 2-Ethylquinazolin-1-oxide 2h. Light orange
crystals. 1H NMR (400 MHz, CDCl3): d 1.39 (3H, t,
J¼7.4 Hz), 3.25 (2H, q, J¼7.4 Hz), 7.64 (1H, t, J¼7.6 Hz),
7.87–7.93 (2H, m), 8.59 (1H, d, J¼8.7 Hz), 8.82 (1H, s).
13C NMR (100 MHz, CDCl3): d 10.1, 26.2, 119.2, 125.2,
127.6, 129.2, 134.9, 143.7, 146.5, 158.0. Anal. Calcd for
C10H10N2O (174.20), MS m/z 174 (M+): C, 68.95; H, 5.79;
N, 16.08. Found C, 68.90; H, 5.85; N, 16.00.
4.2.1.2. 2-Furan-2-yl-quinazolin-1-oxide 2b. Light
orange crystals. H NMR (400 MHz, CDCl3): d 6.73 (1H,
1
dd, J¼3.6, 2.0 Hz), 7.72–7.78 (2H, m), 7.98–8.04 (2H, m),
8.35 (1H, d, J¼3.2 Hz), 8.72 (1H, d, J¼8.4 Hz), 9.03 (1H,
s). 13C NMR (100 MHz, CDCl3): d 112.8, 118.7, 119.5,
123.9, 127.5, 129.1, 134.9, 143.4, 144.0, 145.5, 145.8,
147.1. Anal. Calcd for C12H8N2O2 (212.06), MS m/z 212
(M+): C, 67.92; H, 3.80; N, 13.20. Found: C, 68.42; H,
3.81; N, 13.12.
4.2.2. Improved one-pot procedure for the oxidation of
2a–d in the presence of phase transfer catalyst. To a solu-
tion of 2-aminobenzylamine (2 mmol, 0.244 g) in methanol
(10 mL), aldehyde (2 mmol) was added and the mixture
stirred at room temperature for 1 h. H2O2 (8 mmol, 35%,
0.776 g) and Na2WO4$2H2O (0.1 mmol, 0.033 g) were
added to the mixture and stirring continued for further 1 h.
The solvent was evaporated under vacuum and then the
residue was suspended in chloroform (15 mL). TBAHS
4.2.1.3. 2-(4-Methoxyphenyl)quinazolin-1-oxide 2c.
Gold colored crystals. 1H NMR (400 MHz, CDCl3): d 3.91
(3H, s), 7.04–7.08 (2H, m), 7.70–7.74 (1H, m), 7.96–8.01
(2H, m), 8.77 (1H, d, J¼8.0 Hz), 8.88–8.98 (2H, m), 8.98
(1H, s). 13C NMR (100 MHz, CDCl3): d 55.4, 113.4,

N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
2971
(0.12 mmol, 0.042 g) and H2O2 (1.8 mmol, 35%, 0.175 g)
were added and the mixture stirred for 3 h at room tempera-
ture. The mixture was filtered and water was added to the
mixture. The organic phase was separated and dried over an-
hydrous Na2SO4. Upon filtration the solvent was evaporated.
The isolation procedure is as in the previous general method.
crystals. Mp 129–130 ꢀC. 1H NMR (400 MHz, CDCl3):
d 7.48–7.51 (2H, m), 7.61–7.65(1H, m), 7.90–7.95 (2H, m),
8.07(1H, dd, J¼9.6, 0.8 Hz), 8.55–8.59 (2H, m), 9.46(1H, s).
13C NMR (100 MHz, CDCl3): d 123.6, 127.2, 127.5, 128.6,
128.8, 129.9, 134.3, 136.5, 136.8, 150.7, 160.0, 166.0.
Anal. Calcd for C14H9ClN2 (240.69), MS m/z 240 (M+): C,
69.86; H, 3.77; N, 11.64. Found C, 69.48; H, 3.88; N, 11.19.
4.2.3. Conversion of 2-phenyl-1,2,3,4-tetrahydroquinazo-
lin-1-ol to 2a. To a suspension of 2-phenyl-1,2,3,4-tetra-
hydroquinazolin-1-ol (0.2 mmol, 0.045 g) in chloroform
(10 mL), TBAHS (0.1 mmol, 0.035 g), H2O2 (0.8 mmol,
35%, 0.078 g), and Na2WO4$2H2O (0.01 mmol, 0.003 g)
were added successively and the mixture stirred at room
temperature for 1 h. Water (10 mL) was added to the mixture
and the organic phase was separated, dried over anhydrous
Na2SO4, and filtered. The solvent was evaporated and the
residue recrystallized from hexane or petroleum ether.
4.3.1.5. 2-(3-Nitrophenyl)quinazoline 3f. The com-
pound was isolated from the reaction mixture of 2f. Light
yellow powder. Mp 162–163 ꢀC. 1H NMR (400 MHz,
CDCl3): d 7.67–7.74 (2H, m), 7.96–8.01 (2H, m), 8.14
(1H, dd, J¼9.2, 0.8 Hz), 8.36 (1H, ddd, J¼8.4, 2.4,
1.2 Hz), 8.99 (1H, dt, J¼8.0, 1.2 Hz), 9.51 (1H, m) 9.52
(1H, s). 13C NMR (100 MHz, CDCl3): d 123.85, 124.19,
125.29, 127.49, 128.35, 129.00, 129.81, 134.48, 134.86,
140.11, 149.06, 150.85, 158.92, 161.04. Anal. Calcd for
C14H9N3O2 (251.24), MS m/z 251 (M+): C, 66.93; H, 3.61;
N, 16.73. Found C, 66.50; H, 3.70; N, 16.53.
4.3. Deoxygenation of quinazolin-1-oxides
4.3.1. Synthesis of 3a–g.
4.3.1.6. 2-(3,4-Dimethoxyphenyl)quinazoline 3g. Com-
pound 2g (0.04 mmol, 11 mg) in 4 mL of THF was exposed
to ambient light in four Pyrex NMR tubes for 3.3 h. The
4.3.1.1. 2-Phenylquinazoline 3a. The compound was ob-
tained from the exposure of the solution of 2a (0.23 mmol,
0.05 g) in THF (15 mL) to ambient light for 72 h. The com-
pound was isolated by preparative TLC using ethyl acetate–
petroleum ether (1:4) as an eluent system. Light yellow
powder. Yield (38 mg, 80%). Mp 97–98 ꢀC. 1H NMR
(400 MHz, CDCl3): d 7.49–7.57 (3H, m), 7.61–7.65 (1H,
m), 7.90–7.95 (2H, m), 8.10 (1H, J¼8.4 Hz), 8.61 (2H, dd,
J¼8.0, 2 Hz), 9.48 (1H, s). 13C NMR (100 MHz, CDCl3):
d 123.6, 127.1, 127.3, 128.5, 128.6, 128.7, 130.6, 134.1,
138.1, 150.8, 160.5, 161.1. Anal. Calcd for C14H10N2
(206.24), MS m/z 206 (M+): C, 81.53; H, 4.89; N, 13.58.
Found C, 81.47; H, 5.02; N, 13.62.
1
yield determined by H NMR is 80%. Isolated by means
of preparative TLC. Light yellow powder. Yield (5 mg,
1
47%). Mp 73–75 ꢀC. H NMR (400 MHz, CDCl3): d 3.99
(3H, s), 4.08 (3H, s), 7.02 (1H, d, J¼8.4 Hz), 7.57–7.61 (1H,
m), 7.88–7.92 (2H, m), 8.06 (1H, dd, J¼8.4, 1.2 Hz), 8.20
(1H, d, J¼2 Hz), 8.26 (1H, dd, J¼8.4, 2 Hz), 9.43 (1H, s).
13C NMR (100 MHz, CDCl3): d 55.9, 56.0, 110.9, 111.1,
122.0, 123.4, 126.8, 127.1, 128.4, 134.0, 136.2, 136.4, 149.1,
150.8, 160.4, 160.8. Anal. Calcd for C16H14N2O2 (266.29):
C, 72.16; H, 5.30; N, 10.52. Found: C, 72.00; H, 5.40; N,
10.52.
4.3.1.2. 2-(Furan-2-yl)quinazoline 3b. Compound 2b
(0.06 mmol, 0.013 g) in 6 mL of THF was exposed to ambi-
ent light in six Pyrex NMR tubes for 3.3 h. The yield deter-
mined by 1H NMR is 65%. Isolated by means of preparative
TLC. Brown powder. Yield (3 mg, 25%). Mp 113–114 ꢀC.
1H NMR (400 MHz, CDCl3): d 6.63–6.64 (1H, m), 7.47–
7.50 (1H, m), 7.60–7.64 (1H, m), 7.71 (1H, s), 7.91–7.95
(2H, m), 8.11–8.15 (1H, m), 9.40 (1H, s). 13C NMR
(100 MHz, CDCl3): d 112.3, 114.1, 123.4, 127.3, 128.4,
134.5, 145.4, 150.5, 152.6, 154.2, 160.8. Anal. Calcd for
C12H8N2O (196.2), MS m/z 196 (M+): C, 73.46; H, 4.11;
N, 14.28. Found C, 73.35; H, 4.01; N, 14.35.
4.3.1.7. 2-Ethylquinazoline 3h. Compound 2h
(0.2 mmol, 0.034 g) in 10 mL of THF was exposed to ambi-
ent light in 10 Pyrex NMR tubes for 3.3 h. The yield deter-
mined by 1H NMR is 74%. Attempts to isolate the
compound by preparative TLC failed. The only isolable
product from the reaction mixture was 7h.
4.3.2. Synthesis of indazole. To a solution of 2-amino-
benzylamine 1 (5 mmol, 0.611 g) in MeOH (20 mL), H2O2
(20 mmol, 35%, 1.94 g, 1.7 mL) and Na2WO4$2H2O
(0.25 mmol, 0.082 g) were added and the mixture stirred
for 1 h at room temperature. The solvent was evaporated, wa-
ter was added (20 mL) to the mixture, and then extracted with
chloroform (2ꢂ15 mL). The extracts were combined and
dried over anhydrous Na2SO4, filtered, and the solvent was
evaporated. The residue was recrystallized from ether–petro-
leum ether. Yield (482 mg, 82%). Mp 145–146 ꢀC. 1H NMR
(400 MHz, CDCl3): d 7.11 (1H, t, J¼7.5 Hz), 7.30 (1H, t,
J¼7.5 Hz), 7.43 (1H, d, J¼8.4 Hz), 7.7 (1H, d, J¼8.1 Hz),
8.05 (1H, s), 10.98 (1H, br s). 13C NMR (100 MHz,
CDCl3): d 110.2, 121.3, 121.4, 123.6, 127.3, 135.1, 140.5.
The spectral characteristics of the compound were compared
with those of authentic sample.13
4.3.1.3. 2-(4-Methoxyphenyl)quinazoline 3c. Com-
pound 2b (5 mg, 0.02 mmol) in 2 mL of THF was exposed
to ambient light in two Pyrex NMR tubes for 3.3 h. The yield
determined by 1H NMR is 75%. Isolated by means of prepar-
ative TLC. Light yellow powder. Yield (0.002 g, 43%). Mp
82–84 ꢀC. 1H NMR (400 MHz, CDCl3): d 3.91 (3H, s), 7.05
(2H, d, J¼8.8 Hz), 7.59 (1H, t, J¼7.6 Hz), 7.87–7.92 (2H,
m), 8.06 (1H, d, J¼8.8 Hz), 8.58 (2H, d, J¼8.8 Hz), 9.43
(1H, s). 13C NMR (100 MHz, CDCl3): d 55.4, 114.0, 123.3,
126.9, 127.2, 128.3, 130.3, 134.2, 160.5, 160.8, 162.0.
Anal. Calcd for C15H12N2O (236.27), MS m/z 236 (M+): C,
76.25; H, 5.12; N, 11.86. Found C, 76.45; H, 4.95; N, 11.70.
4.4. 2-(4-Chlorophenyl)quinazolin-3-oxide
4.3.1.4. 2-(4-Chlorophenyl)quinazoline 3d. The com-
pound was isolated from the reaction mixture of 2d. Yellow
The compound was isolated from the reaction mixture of 2d.
Light orange crystals. Yield (102 mg, 8%). Mp 161–162 ꢀC

2972
N. Coxskun, M. C¸ etin / Tetrahedron 63 (2007) 2966–2972
1
(with decomposition). H NMR (400 MHz, CDCl3): d 7.49
(2H, d, J¼8.0 Hz), 7.63–7.79 (3H, m), 8.02 (1H, d,
J¼8.4 Hz), 8.39 (2H, d, J¼8.0 Hz), 9.00 (1H, s). 13C
NMR (100 MHz, CDCl3): d 123.9, 124.1, 128.3, 128.5,
129.9, 130.1, 131.8, 132.0, 137.4, 141.3, 142.1, 154.1.
Anal. Calcd for C14H9ClN2O (256.69): C, 65.51; H, 3.53;
N, 10.91. Found. C, 65.40; H, 3.60; N, 11.03.
ambient light in 10 Pyrex NMR tubes for 3.3 h. Isolated
by means of preparative TLC. Light yellow oil. Yield
(3 mg, 9%). H NMR (400 MHz, CDCl3): d 1.29 (3H, t,
1
J¼7.2 Hz), 2.51 (2H, q, J¼7.2 Hz), 7.22 (1H, dt, J¼7.2,
0.8 Hz), 7.62 (1H, dt, J¼7.2, 2 Hz), 7.68 (1H, dd, J¼7.2,
2 Hz), 8.77 (1H, d, J¼8.4 Hz), 9.93 (1H, s), 11.16 (1H, br
s). 13C NMR (100 MHz, CDCl3): d 9.5 (CH3), 31.59
(CH2), 119.9 (C6H), 121.6 (C2), 122.7 (C5H), 136.1
(C4H), 136.2 (C6H), 141.1 (C1), 173.5 (amide C]O),
195.6 (aldehyde C]O). Anal. Calcd for C10H11NO2
(177.2), MS m/z 177 (M+): C, 67.78; H, 6.26; N, 7.90.
Found: C, 67.40; H, 6.00; N, 7.30.
4.5. 2-(4-Methoxyphenyl)quinazolin-4(3H)-one
From the reaction mixture of 2c. Light yellow crystals. Yield
(24 mg, 2%). Mp 237–239 ꢀC. IR (KBr): nC]O 1678 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d 3.91 (3H, s), 7.07 (2H, d,
J¼7.6 Hz), 7.45–7.49 (1H, m), 7.76–7.81 (2H, m), 8.15–
8.18 (2H, m), 8.30–8.32 (1H, m), 11.0 (1H, br s). 13C
NMR (100 MHz, CDCl3): d 55.5, 114.5, 120.6, 125.0, 126.3,
126.4, 127.7, 128.9, 134.9, 149.6, 151.3, 162.5, 163.5. Anal.
Calcd for C15H12N2O2 (252.27), MS m/z 252 (M+): C, 71.42;
H, 4.79; N, 11.10. Found C, 71.37; H, 4.72; N, 11.07.
Acknowledgements
ꢀ
Scientific Research Project Commission of Uludag Univer-
sity is gratefully acknowledged for its financial support
(State Planning Organization Project No. 2001-2).
References and notes
4.6. 1-Phenylquinazolin-2(1H)-one 5a
A solution of compound 2a (0.1 mmol, 0.022 g) in CDCl3
(4 mL) was exposed to ambient light for a day and then
left overnight. The compound was isolated by preparative
TLC. Yield (3 mg, 14%). 1H NMR (400 MHz, CDCl3):
d 6.70 (1H, d, J¼8.8 Hz), 7.26–7.35 (3H, m), 7.52–7.64
(4H, m), 7.79 (1H, dd, J¼7.6, 1.6 Hz), 9.26 (1H, s). 13C
NMR (100 MHz, CDCl3): d 115.4, 116.6, 122.9, 128.4,
128.8, 129.3, 130.4, 135.3, 136.8, 144.3, 155.5, 168.2. Anal.
Calcd for C14H10N2O (222.24), MS m/z 222 (M+): C, 75.66;
H, 4.54; N, 12.60. Found: C, 75.22; H, 4.60; N, 12.17.
1. (a) Witt, A.; Bergman, J. Curr. Org. Chem. 2003, 7, 659–677;
(b) Dyakonov, A. L.; Telezhenetskaya, M. V. Khim. Prir.
Soedin. 1997, 3, 297–351; (c) Spence, G. G.; Taylor, E. C.;
Buchardt, O. Chem. Rev. 1970, 70, 231–265.
2. (a) Michael, J. P. Nat. Prod. Rep. 1999, 16, 697–709; (b)
Michael, J. P. Nat. Prod. Rep. 2002, 19, 742–760; (c)
Michael, J. P. Nat. Prod. Rep. 2003, 20, 476–493.
3. (a) Touroutoglou, N.; Pazdur, R. Clin. Cancer Res. 1996, 2,
227–243; (b) Jackman, A. L.; Boyle, F. T.; Harrap, K. R.
Invest. New Drug 1996, 14, 305–316; (c) Sielecki, T. M.;
Johnson, T. L.; Liu, J.; Muckelbauer, J. K.; Grafstrom, R. H.;
Cox, S.; Boylan, J.; Burton, C. R.; Chen, H.; Smallwood, A.;
Chang, C. H.; Boisclair, M.; Benfield, P. A.; Trainora, G. L.;
Seitza, S. P. Bioorg. Med. Chem. Lett. 2001, 11, 1157–1160;
(d) Bonomi, P. E. Expert Opin. Inv. Drug. 2003, 12, 1395–1401.
4. (a) Armarego, W. L. F. Advanced Heterocyclic Chemistry;
Academic: New York, NY, 1963; Vol. 1, pp 253–309; (b)
Armarego, W. L. F. Adv. Heterocycl. Chem. 1979, 24, 1–61.
5. Gilchrist, T. L. Six-membered ring compounds with two
or more heteroatoms. In Heterocyclic Chemistry; Pitman:
London, 1985; pp 327–330.
4.7. 2-Phenoxyquinazoline 6a
A solution of compound 2a (0.1 mmol, 0.022 g) in CDCl3
(4 mL) was exposed to ambient light for a day and left over-
night. Light yellow crystals. Yield (6 mg, 27%). Mp 114–
115 ꢀC. 1H NMR (400 MHz, CDCl3): d 7.26–7.30 (3H, m),
7.47 (2H, t, J¼7.2 Hz), 7.51 (1H, t, J¼8.0 Hz), 7.80–7.84
(2H, m), 7.90 (1H, d, J¼8.0 Hz), 9.30 (1H, s). 13C NMR
(100 MHz, CDCl3): d 121.7, 122.4, 125.2, 125.8, 127.2,
127.3, 129.6, 134.8, 152.0, 153.3, 162.3, 164.0. Anal. Calcd
for C14H10N2O (222.24), MS m/z 222 (M+): C, 75.66; H,
4.54; N, 12.60. Found: C, 75.34; H, 4.63; N, 12.30.
6. (a) Sinkkonen, J.; Zelenin, K. N.; Potapov, A. A.; Lagoda, I. V.;
Alekseyev, V. V.; Pihlaja, K. Tetrahedron 2003, 59, 1939–1950;
€
€
ꢁ ꢁ
€ €
(b) Goblyos, A.; Lazar, L.; Fulop, F. Tetrahedron 2002, 58,
4.7.1. N-(2-Formylphenyl)furan-2-carboxamide 7b.
Compound 2b (0.06 mmol, 0.013 g) in 6 mL of THF was ex-
posed to ambient light in six Pyrex NMR tubes for 3.3 h. The
yield determined by 1H NMR is 30%. Isolated by means of
preparative TLC. Light yellow powder. Yield (2 mg, 14%).
1011–1016.
7. Sternbach, L. H.; Kaiser, S.; Reeder, E. J. Am. Chem. Soc. 1960,
82, 475–480.
8. Coxskun, N.; C¸ etin, M. Tetrahedron Lett. 2004, 45, 8973–8975.
9. Stempel, A.; Douvan, I.; Sternbach, L. H. J. Org. Chem. 1968,
33, 2963–2966.
1
Mp 98–100 ꢀC. H NMR (400 MHz, CDCl3): d 6.57–6.59
(1H, m), 7.27–7.30 (2H, m), 7.64–7.69 (2H, m), 7.73 (1H,
dd, J¼7.6, 1.6 Hz), 8.89 (1H, d, J¼8.8 Hz), 10.01 (1H, s),
12.09 (1H, s). 13C NMR (100 MHz, CDCl3): d 112.4,
115.7, 120.1, 123.1, 136.1, 136.2, 145.2, 195.5, C]O.
Anal. Calcd for C12H9NO3 (215.2), MS m/z 215 (M+): C,
66.97; H, 4.22; N, 6.51. Found: C, 66.85; H, 4.10; N, 6.35.
10. The photochemistry of the heteroaromatic N-oxides11 is re-
viewed by Albini and Alpegiani and it is seen from the litera-
ture covered here that the rearrangements of the N-oxides are
assumed to proceed through the intermediate oxaziridines,
which are never isolated and their reactions are investigated.
11. Albini, A.; Alpegiani, M. Chem. Rev. 1984, 84, 43–71.
12. Field, G. F.; Sternbach, L. H. J. Org. Chem. 1968, 33, 4438–
4440.
4.7.2. N-(2-Formylphenyl)propionamide 7h. Compound
2h (0.2 mmol, 0.034 g) in 10 mL of THF was exposed to
13. SDBSWeb: http://www.aist.go.jp/RIODB/SDBS/.