ABNO-Catalyzed Aerobic Oxidative Synthesis of 2-Substituted 4H-3,1-Benzoxazines and Quinazolines

Article abstract of DOI:10.1002/ejoc.201700384

A new transition-metal-free 9-azabicyclo[3.3.1]nonan-N-oxyl (ABNO) catalyzed aerobic oxidative synthesis of 2-substituted 4H-3,1-benzoxazines and quinazolines has been developed through cascade reaction of aldehydes with 2-aminobenzyl alcohols and 2-amino

Full text of DOI:10.1002/ejoc.201700384

DOI: 10.1002/ejoc.201700384
Full Paper
Aerobic Oxidation | Very Important Paper |
ABNO-Catalyzed Aerobic Oxidative Synthesis of 2-Substituted
4H-3,1-Benzoxazines and Quinazolines
Jiaqi Ma,[a] Yan Wan,[a] Chao Hong,[a] Meichao Li,[a] Xinquan Hu,[a] Weimin Mo,[a]
Baoxiang Hu,[a] Nan Sun,[a] Liqun Jin,[a] and Zhenlu Shen*[a]
Abstract: A new transition-metal-free 9-azabicyclo[3.3.1]non- benzyl alcohols and 2-aminobenzylamines, respectively. Under
an-N-oxyl (ABNO) catalyzed aerobic oxidative synthesis of 2- the optimal reaction conditions, the two kinds of heterocycles
substituted 4H-3,1-benzoxazines and quinazolines has been de- were obtained in 72–97 % isolated yield.
veloped through cascade reaction of aldehydes with 2-amino-
Introduction
tive. In 2016, an efficient approach for the synthesis of quin-
azolines by aerobic photooxidation with an iodine reagent at
room temperature was developed by Itoh et al.[12] Unfortu-
nately, no product was formed when an aliphatic aldehyde was
used as the substrate. Previously, Han et al. reported the 4-
methoxy-TEMPO-catalyzed aerobic oxidative reaction for the
synthesis of five-membered heterocyclic rings such as 2-substi-
tuted benzoxazoles, benzothiazoles, and benzimidazoles.[13] As
an extension of that system, they successfully synthesized 2-
arylquinazolines by aerobic oxidative reaction of arylmethan-
amines with 2-aminophenyl ketones and 2-aminobenzalde-
hydes using 4-hydroxy-TEMPO as the catalyst.[14] Then they at-
tempted to utilize 4-hydroxy-TEMPO as the catalyst to produce
2-substituted quinazolines. However, the yield was very poor;
to improve the yield, the copper-catalyzed aerobic oxidative re-
action of aldehydes with 2-aminobenzyl alcohols and 2-amino-
benzylamines was developed.[15] Therefore, the development of
a transition-metal-free catalytic system is highly desirable.
In recent years, the structurally less hindered bicyclic 9-azabi-
cyclo[3.3.1]nonan-N-oxyl (ABNO) and its derivatives have been
reported for the efficient catalytic oxidation of structurally hin-
dered alcohols[16] or the catalytic oxidation of primary amines
into nitriles.[17] Moreover, the synthetic route of ABNO is short
4H-3,1-Benzoxazines and quinazolines are present in bioactive
natural products and in synthetic pharmaceutical compounds,
which exhibit important biological properties.[1] These nitro-
gen-containing heterocycles have been extensively studied as
the core structural skeletons in a variety of drugs. For example,
the GABA receptor inhibitor as an anxiolytic and anticonvulsant
agent (etifoxine),[2] the pancreatic lipase inhibitor for the treat-
ment of obesity (cetilistat),[3] the α-adrenergic blockers to treat
high blood pressure, anxiety, and panic disorder (prazosin),[4]
and the EGFR inhibitor (icotinib).[5] Therefore, the development
of efficient and environmentally friendly synthetic strategies for
the preparation of substituted 4H-3,1-benzoxazines and quinaz-
olines has received much attention. A number of transition-
metal-catalyzed reactions are available for the synthesis of sub-
stituted quinazolines, including Cu, Rh, Pt, Ir, and Zn.[6] Only a
few methods were reported for the synthesis of substituted 4H-
3,1-benzoxazines.[7] In addition, the condensation of 2-amino-
benzyl alcohols or 2-aminobenzylamines with aldehydes fol-
lowed by oxidation of the intermediate with strong oxidants
such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or
tetrachloro-1,4-benzoquinone (TCQ),[8] NaClO,[9] and MnO2
provides a simple way to synthesize 4H-3,1-benzoxazines or
quinazolines. However, large excess amounts of nonrenewable
or toxic oxidants were required in these methods.
[10]
In the past decades, molecular oxygen has received much
attention in catalytic oxidative reactions due to its remarkable
advantages such as abundant, inexpensive, and clean.[11] There
is no doubt that molecular oxygen as oxidant for the synthesis
of 4H-3,1-benzoxazines and quinazolines was the best alterna-
[a] College of Chemical Engineering, Zhejiang University of Technology,
Hangzhou 310014, People's Republic of China
E-mail: zhenlushen@zjut.edu.cn
www.zjut.edu.cn
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201700384.
Scheme 1. New method for the synthesis of 2-substituted 4H-3,1-benzox-
azines and quinazolines.
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and simple through three steps. As a part of our research pro- almost fully transformed to 4a (Table 1, Entry 2). As we know,
grams aimed at nitroxyl-catalyzed reactions,[16h,18] herein we re- reagent-grade KOH usually has transition-metal contaminants.
port the ABNO-catalyzed one-pot aerobic oxidative reaction of Thus, semiconductor-grade KOH in 99.99 % purity was exam-
aldehydes with 2-aminobenzyl alcohols and 2-aminobenzyl-
amines to prepare 2-substituted 4H-3,1-benzoxazines and quin-
azolines (Scheme 1).
ined, and the excellent selectivity to 4a was maintained. When
30 mol-% KOH was added alone, the selectivity to 4a was only
4 % (Table 1, Entry 3). When air was employed, the selectivity
to 4a dropped to 74 % (Table 1, Entry 4). Other nitroxyl radicals
(Scheme 2), such as TEMPO, 4-HO-TEMPO, 4-acetamido-TEMPO,
keto-ABNO, and 4-acetyloxy-ABNO were also investigated. The
results display that ABNO is the most efficient catalyst (Table 1,
Entries 2 and 5–9). When N-hydroxyphthalimide (NHPI) was
used, the yield was poor (Table 1, Entry 10). An investigation of
the effect of various bases revealed that KOH gave the highest
yield of product 4a (Table 1, Entries 2 and 11–16). Among vari-
ous solvents screened, toluene gave the best result (Table 1,
Entries 2 and 17–20). When the amount of KOH was reduced
to 20 and 10 mol-%, the selectivity to 4a went down to 88 and
73 %, respectively (Table 1, Entries 21 and 22). Reducing the
amount of ABNO also led to lower yields (Table 1, Entries 23–
25). When the reaction temperatures were decreased to 70 and
Results and Discussion
The study was initiated by conducting the reaction of 2-amino-
benzyl alcohol (1a) with benzaldehyde (2a) (Table 1). Firstly, the
reaction of 1a and 2a was carried out in toluene with 10 mol-
% ABNO under atmospheric pressure of O2 in a balloon at 80 °C.
After 4 h, the conversion based on starting material 2a was
95 %; the selectivity to target product 4a was only 13 %, and
the selectivity to the intermediate product 3a was 85 %
(Table 1, Entry 1). According to previous reports,[19] a base such
as KOH could promote a TEMPO-catalyzed oxidative reaction.
To our delight, when 30 mol-% KOH was added, the conversion
reached up to 98 %, and the selectivity to 4a was increased to 60 °C, the selectivity to 4a was decreased to 85 and 40 %, re-
99 %, which concludes that the intermediate product 3a was spectively (Table 1, Entries 26 and 27). After detailed explora-
Table 1. Optimization on the catalytic aerobic oxidative synthesis of 2-substituted 4H-3,1-benzoxazines.[a]
Entry
Nitroxyl
Catalyst
[mol-%]
Additive
[mol-%]
Solvent
T
[°C]
Conversion[b]
Selectivity[b]
[%]
[%]
2a
3a
4a
1
2
3
ABNO
ABNO
–
10
10
–
–
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH3CN
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
reflux
80
80
80
80
80
70
60
95
98
95
96
96
97
96
98
95
64
95
80
91
65
96
96
95
89
93
81
97
97
94
94
95
98
95
85
13
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
NaOH(30)
Na2CO3(30)
K2CO3(30)
Cs2CO3(30)
Et3N(30)
tBuOK(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(20)
KOH(10)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
KOH(30)
trace
92
25
80
77
83
50
56
94
28
79
76
41
83
17
57
44
30
9
99(95[d]
4
)
4[c]
5
ABNO
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
8
74
10
13
10
49
42
5
68
12
9
TEMPO
4-HO-TEMPO
4-acetamido-TEMPO
keto-ABNO
4-acetyloxy-ABNO
NHPI
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
ABNO
25
9
74
35
50
67
85
88
73
77
65
38
85
40
DMF
xylene
ethyl acetate
toluene
toluene
toluene
toluene
toluene
toluene
toluene
11
17
22
34
56
15
59
6
5
10
10
ABNO
[a] Reaction conditions: 1a (2 mmol), 2a (2 mmol), solvent (4 mL), O2 balloon. [b] Determined by GC with area normalization method. [c] Air was used instead
of O2. [d] Isolated yield.
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tion of the reaction conditions with 1a and 2a as the substrates, chlorophenyl)methanol was not very efficient under the opti-
we chose 10 mol-% ABNO and 30 mol-% KOH in toluene at mal reaction conditions; 4z was obtained in 81 % isolated yield
80 °C with an O2 balloon as the optimal reaction conditions. when the amount of ABNO was increased to 0.5 equiv. (Table 2;
Hence, 4a could be obtained in 95 % isolated yield in 4 h 4z).
(Table 1, Entry 2).
Table 2. ABNO-catalyzed aerobic oxidative synthesis of 2-substituted 4H-3,1-
benzoxazines.[a]
Scheme 2. Structure of different types of nitroxyl radicals.
With the optimal reaction conditions, a variety of 2-substi-
tuted 4H-3,1-benzoxazines were synthesized. As shown in
Table 2, the reaction system was able to tolerate a wide range
of functional groups. Compound 4a could be obtained in 91 %
isolated yield on a gram scale in 8 h (Table 2; 4a). The reaction
worked well between 2-aminobenzyl alcohol and various
benzaldehydes with electron-donating groups, including 2-, 3-,
4-CH3, 4-iPr, 4-tBu, and 4-SCH3, and good to excellent isolated
yields were obtained in 4–6 h (Table 2; 4b–g). When benzalde-
hydes with electron-withdrawing groups (2-, 3-, 4-Br, 2-Cl, 4-F,
4-CF3) were utilized, the reactions also proceeded well (Table 2;
[a] Reaction conditions: 1 (2 mmol), 2 (2 mmol), ABNO (10 mol-%), KOH
(30 mol-%), toluene (4 mL), O2 balloon, 80 °C. Results are shown as follows:
4h–m). It is worth noting that the reaction of 2-aminobenzyl
alcohol with 4-fluorobenzaldehyde resulted in the formation of
product 4l in 95 % isolated yield (Table 2; 4l). In addition,
heteroaromatic aldehydes could also be used as the substrates.
We were pleased to find that the isolated yield of 4o could
reaction time, isolated yield. [b] On a gram scale: 1a (20 mmol, 2.46 g), 2a
(20 mmol, 2.12 g), toluene (40 mL), O2 balloon, 80 °C. [c] 0.5 equiv. ABNO
was used.
Having successfully achieved the ABNO-catalyzed aerobic
reach up to 93 % in 5 h (Table 2; 4o). However, the isolated oxidative synthesis of 2-substituted 4H-3,1-benzoxazines, we ex-
yields were somewhat lower when furan-2-carbaldehyde and panded the catalytic system to the synthesis of 2-substituted
5-bromothiophene-2-carbaldehyde were employed (75 %) quinazolines (Table 3). Initially, when 2-aminobenzylamine (2a),
(Table 2; 4n and 4p). Compound 4q was obtained in 79 % yield 10 mol-% of ABNO, and 30 mol-% of KOH were added together
when 1-naphthaldehyde was used as the substrate (Table 2; to toluene, target product 6a was obtained as expected, but
4q). Moreover, when cinnamaldehyde was involved, the iso- the isolated yield was only about 50–60 %. Whether the reac-
lated yield of 4r was also as high as 91 % (Table 2; 4r). As we tion conditions were enhanced or the reaction time was pro-
know that aliphatic aldehydes were usually unsuitable in previ- longed, the starting materials were unable to react completely.
ous reported methods due to the inherent difficulty in activat- Thus, we modified the reaction procedure. Firstly, 2-amino-
ing them compared to aromatic ones.[9,15] Nonetheless, the typ- benzylamine and 2a were allowed to complete condensation
ical aliphatic aldehyde n-butyraldehyde was suitable in the re- (2–3 h, monitored by TLC), then 10 mol-% of ABNO and 30 mol-
action system, and the GC yield of 4s was 99 %. However, 4s % of KOH were added, and the reaction system was charged
was unstable on a gel column, and 73 % isolated yield was with an oxygen balloon. To our delight, the yield of 6a was
obtained through flash column chromatography (Table 2; 4s). raised up to 97 % in 11 h (Table 3; 6a). The reaction between 2-
This catalytic system also showed a broad scope for the substi- aminobenzylamine and benzaldehydes with electron-donating
tuted 2-aminobenzyl alcohols. It is obvious that when 2-amino- groups (2-, 3-, 4-CH3, and 4-OCH3) resulted in the formation of
benzyl alcohols with electron-donating groups (CH3, OCH3) the corresponding 2-substituted quinazolines in 91–95 % yield
were chosen as the reactants, good to excellent yields could be (Table 3; 6b–e). This method also worked well with benzalde-
obtained (Table 2; 4t–y). However, the reaction of (2-amino-5- hydes having electron-withdrawing groups (2-, 3-, 4-Br, 4-F, and
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4-NO2) (Table 3; 6f–j). Furthermore, the reactions also per- KOH [Scheme 3, Equation (4)]. These results show that KOH can
formed well when furan-2-carbaldehyde, thiophene-2-carbalde- accelerate the regeneration of ABNO from ABNOH.
hyde, and nicotinaldehyde were involved, and yields of 89–92 %
were achieved (Table 3; 6k–m). When 1-naphthaldehyde was
used as the substrate, 2-(naphthalen-1-yl)quinazoline (6n) was
obtained in 90 % yield (Table 3; 6n). Notably, aliphatic alde-
hydes reacted with 2-aminobenzylamine to give the corre-
sponding products in 83–96 % yield (Table 3; 6o–s). In addition,
2-aminobenzylamines with an electron-donating group (OCH3)
or an electron-withdrawing group (Cl) also worked well, and
good yields could be obtained (Table 3; 6t and 6u).
Table 3. ABNO-catalyzed aerobic oxidative synthesis of 2-substituted quin-
azolines.[a]
Scheme 3. Control experiments for mechanism studies.
On the basis of the above observations and relevant litera-
ture,[12–14] we propose a plausible mechanism for the formation
of 2-substituted 4H-3,1-benzoxazines (Scheme 4). The first step
is the condensation between 1 and 2 in toluene, and intermedi-
ate 3 is formed. The benzyl hydrogen atom of 3 is then trans-
ferred to ABNO through a hydrogen abstraction step, resulting
in the corresponding radical 8. ABNOH is formed at the same
time, which can be reoxidized to ABNO by oxygen with the
help of KOH. Then, the second hydrogen abstraction happens
between radical 8 and ABNO or oxygen to produce the final
product 4.
[a] Reaction conditions: 5 (2 mmol), 2 (2 mmol), ABNO (10 mol-%), KOH
(30 mol-%), toluene (4 mL), O2 balloon, 80 °C. Results are shown as follows:
reaction time, isolated yield. [b] The product was recrystallized from toluene.
To gain some insight into the possible reaction mechanism,
several control experiments were carried out (Scheme 3). When
3a was isolated and then allowed to react under the optimal
reaction conditions, 3a was almost fully transformed into 4a,
which indicates that 3a is an intermediate of the catalytic cycle
[Scheme 3, Equation (1)]. It was found that 1a and 2a could
react completely to form 4a when 1 equiv. of ABNO was used
Scheme 4. Plausible mechanism for the ABNO-catalyzed aerobic oxidative
in the absence of KOH [Scheme 3, Equation (2)]. Then, ABNOH
(7) was prepared according to the literature,[20] and a reaction
with KOH was performed under O2 for 15 min. The color of the
reaction solution turned to red, which indicates that ABNO was
generated, and ABNO was isolated in 78 % yield [Scheme 3,
synthesis of 2-substituted 4H-3,1-benzoxazines.
Conclusions
Equation (3)]. However, only a trace amount of ABNO was ob- A simple, green, and efficient ABNO-catalyzed aerobic oxidative
tained when the reaction was carried out in the absence of synthesis of 2-substituted 4H-3,1-benzoxazines and quin-
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2-p-Tolyl-4H-benzo[d][1,3]oxazine (4d): Yield: 383.6 mg, 86 %.
White solid; m.p. 104–105 °C. H NMR (500 MHz, CDCl3): δ = 8.04–
azolines has been developed. Under the optimal reaction condi-
tions, a wide range of products were synthesized in good to
excellent yields. In addition, the role of KOH was discussed
through control experiments. KOH can accelerate the regenera-
tion of ABNO from ABNOH.
1
8.03 (m, 2 H), 7.33–7.25 (m, 4 H), 7.20–7.16 (m, 1 H), 7.02 (d, J =
7.2 Hz, 1 H), 5.39 (s, 2 H), 2.43 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 157.9, 141.9, 139.9, 129.6, 129.0, 128.9, 128.0, 126.2,
124.5, 123.7, 122.4, 66.4, 21.6 ppm. MS (EI): m/z (%) = 223.12 (100)
[M]+.
Experimental Section
2-(4-Isopropylphenyl)-4H-benzo[d][1,3]oxazine
(4e):
Yield:
406.6 mg, 81 %. White solid; m.p. 83–85 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.09–8.07 (m, 2 H), 7.34–7.30 (m, 4 H), 7.20–7.17 (m, 1
H), 7.02 (d, J = 7.4 Hz, 1 H), 5.39 (s, 2 H), 3.03–2.94 (m, 1 H), 1.30 (d,
J = 7.4 Hz, 6 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 157.9, 152.7,
139.8, 129.9, 128.9, 128.1, 126.3, 126.2, 124.5, 123.6, 122.3, 66.4, 34.2,
23.8 ppm. ESI-HRMS: m/z calcd. for C17H17NO + H+ 252.1383; found
252.1378.
General Remarks: ABNO, keto-ABNO, and 4-acetyloxy-ABNO were
prepared in our laboratory according to the literature.[16a] Other
chemicals were purchased from suppliers and used without any
1
further treatment. H NMR spectra were recorded at 500 MHz. 13C
NMR spectra were recorded at 125 MHz. CDCl3 was used as the
solvent with tetramethylsilane (TMS) as the internal standard. GC
analyses were conducted with a flame ionization detector (FID) and
a DB-5 capillary column. GC–MS (EI, 70 eV) was performed with a
DB-5 MS capillary column. HR mass spectra were recorded with an
electrospray quadrupole time-of-flight (ESI-Q-TOF) mass spectrome-
ter. Melting points were measured by using a melting point instru-
ment.
2-(4-tert-Butylphenyl)-4H-benzo[d][1,3]oxazine
(4f):
Yield:
472.2 mg, 89 %. Pale yellow solid; m.p. 77–80 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.10–8.07 (m, 2 H), 7.49–7.46 (m, 2 H), 7.33–7.32 (m, 2
H), 7.21–7.03 (m, 1 H), 7.02 (d, J = 1.2 Hz, 1 H), 5.39 (s, 2 H), 1.37 (s,
9 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.0, 155.1, 139.7, 129.4,
128.9, 127.9, 126.3, 125.2, 124.5, 123.7, 122.3, 66.4, 34.9, 31.2 ppm.
ESI-HRMS: m/z calcd. for C18H19NO + H+ 266.1539; found 266.1537.
General Procedure for the Synthesis of 2-Substituted 4H-3,1-
Benzoxazines from 2-Aminobenzyl Alcohols and Aldehydes
(Table 2): To a 50 mL round-bottom flask were added 2-amino-
benzyl alcohol (2 mmol), aldehyde (2 mmol), ABNO (0.2 mmol,
28.0 mg), KOH (0.6 mmol, 33.6 mg), and toluene (4 mL). The mixture
was stirred at 80 °C under O2 (balloon) for several hours. After com-
pletion of the reaction (monitored by GC or TLC), the resulting mix-
ture was concentrated under reduced pressure and purified by
column chromatography to give the desired products 4a–z.
2-[4-(Methylthio)phenyl]-4H-benzo[d][1,3]oxazine (4g): Yield:
367.2 mg, 72 %. Pale yellow solid; m.p. 137–138 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.07–8.05 (m, 2 H), 7.34–7.27 (m, 4 H), 7.20–
7.17 (m, 1 H), 7.02 (d, J = 7.5 Hz, 1 H), 5.39 (s, 2 H), 2.54 (s, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 157.5, 143.3, 139.7, 129.0,
128.6, 128.3, 126.3, 125.2, 124.5, 123.7, 122.3, 66.4, 15.1 ppm. ESI-
HRMS: m/z calcd. for C15H13NOS + H+ 256.0791; found 256.0803.
General Procedure for the Synthesis of 2-Substituted Quin-
azolines from 2-Aminobenzylamines and Aldehydes (Table 3):
To a 50 mL round-bottom flask were added 2-aminobenzylamine
(2 mmol), aldehyde (2 mmol), and toluene (4 mL). The mixture was
stirred at 80 °C until the condensation was complete (about 3 h,
monitored by TLC). Then ABNO (0.2 mmol, 28.0 mg) and KOH
(0.6 mmol, 33.6 mg) were added, and the mixture was stirred at
80 °C under O2 (balloon) for several hours. After completion of the
reaction (monitored by TLC), the resulting mixture was concen-
trated under reduced pressure and purified by column chromatog-
raphy to give the desired products 6a–u.
2-(2-Bromophenyl)-4H-benzo[d][1,3]oxazine
(4h):
Yield:
512.6 mg, 89 %. Pale yellow oil. 1H NMR (500 MHz, CDCl3): δ = 7.73–
7.71 (m, 1 H), 7.67–7.65 (m, 1 H), 7.41–7.37 (m, 1 H), 7.36–7.30 (m,
3 H), 7.26–7.22 (m, 1 H), 7.04 (d, J = 7.8 Hz, 1 H), 5.46 (s, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 158.7, 139.1, 134.8, 133.5, 131.6,
131.2, 129.0, 127.3, 127.1, 124.8, 123.8, 122.1, 122.0, 66.5 ppm. MS
(EI): m/z (%) = 286.96 (100) [M]+.
2-(3-Bromophenyl)-4H-benzo[d][1,3]oxazine (4i): Yield: 489.6 mg,
1
85 %. Yellow solid; m.p. 106–109 °C. H NMR (500 MHz, CDCl3): δ =
8.30 (t, J = 3.5 Hz, 1 H), 8.09–8.07 (m, 1 H), 7.64–7.61 (m, 1 H), 7.35–
7.29 (m, 3 H), 7.22–7.19 (m, 1 H), 7.03–7.01 (m, 1 H), 5.40 (s, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 156.1, 139.2, 134.4, 134.2,
130.9, 129.7, 129.0, 126.8, 126.4, 124.8, 123.7, 122.4, 122.1, 66.5 ppm.
MS (EI): m/z (%) = 286.82 (42) [M]+, 76.04 (100).
2-Phenyl-4H-benzo[d][1,3]oxazine (4a): Yield: 3.80 g, 91 %
(20 mmol scale). White solid; m.p. 92–93 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.16–8.14 (m, 2 H), 7.53–7.49 (m, 1 H), 7.47–7.43 (m, 2
H), 7.34–7.29 (m, 2 H), 7.21–7.18 (m, 1 H), 7.03 (d, J = 7.2 Hz, 1 H),
5.41 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 157.7, 139.7, 132.4,
131.4, 129.0, 128.2, 128.0, 126.4, 124.6, 123.7, 122.3, 66.4 ppm. MS
(EI): m/z (%) = 209.11 (100) [M]+.
2-(4-Bromophenyl)-4H-benzo[d][1,3]oxazine
(4j):
Yield:
501.1 mg, 87 %. Pale yellow solid; m.p. 144–145 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.03–8.00 (m, 2 H), 7.60–7.57 (m, 2 H), 7.35–
7.27 (m, 2 H), 7.22–7.19 (m, 1 H), 7.04–7.02 (m, 1 H), 5.41 (s, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 156.8, 139.4, 131.5, 131.3,
129.5, 129.1, 126.7, 126.2, 124.7, 123.8, 122.1, 66.5 ppm. MS (EI): m/z
(%) = 286.96 (98) [M]+, 288.97 (100).
2-o-Tolyl-4H-benzo[d][1,3]oxazine (4b): Yield: 414.8 mg, 93 %.
Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 7.84 (d, J = 7.4 Hz, 1
H), 7.40–7.29 (m, 5 H), 7.24–7.21 (m, 1 H), 7.04 (d, J = 7.4 Hz, 1 H),
5.40 (s, 2 H), 2.65 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.6,
139.5, 138.1, 132.5, 131.1, 130.4, 129.7, 128.9, 126.5, 125.6, 124.5,
123.6, 121.9, 66.0, 21.3 ppm. ESI-HRMS: m/z calcd. for C15H13NO +
H+ 224.1070; found 224.1062.
2-(2-Chlorophenyl)-4H-benzo[d][1,3]oxazine
(4k):
Yield:
448.2 mg, 92 %. Yellow oil. 1H NMR (500 MHz, CDCl3): δ = 7.76–7.75
(m, 1 H), 7.48–7.46 (m, 1 H), 7.42–7.38 (m, 1 H), 7.36–7.33 (m, 2 H),
7.31–7.28 (m, 1 H), 7.26–7.22 (m, 1 H), 7.05 (d, J = 7.2 Hz, 1 H), 5.45
(s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.1, 139.2, 133.3,
132.8, 131.4, 131.1, 130.3, 129.0, 127.0, 126.7, 124.8, 123.8, 122.1,
66.4 ppm. MS (EI): m/z (%) = 243.06 (100) [M]+.
2-m-Tolyl-4H-benzo[d][1,3]oxazine (4c): Yield: 343.4 mg, 77 %.
Pale yellow solid; m.p. 63–65 °C. 1H NMR (500 MHz, CDCl3): δ =
8.00–7.94 (m, 2 H), 7.37–7.31 (m, 4 H), 7.21–7.18 (m, 1 H), 7.03 (d,
J = 7.2 Hz, 1 H), 5.40 (s, 2 H), 2.44 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 157.9, 139.7, 137.9, 132.3, 132.2, 128.9, 128.5, 128.1,
2-(4-Fluorophenyl)-4H-benzo[d][1,3]oxazine (4l): Yield: 431.3 mg,
1
126.3, 125.1, 124.5, 123.6, 122.3, 66.3, 21.3 ppm. ESI-HRMS: m/z 95 %. White solid; m.p. 103–106 °C. H NMR (500 MHz, CDCl3): δ =
calcd. for C15H13NO + H+ 224.1070; found 224.1066.
8.18–8.14 (m, 2 H), 7.35–7.28 (m, 2 H), 7.22–7.18 (m, 1 H), 7.15–7.12
3339 © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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(m, 2 H), 7.02 (d, J = 7.3 Hz, 1 H), 5.39 (s, 2 H) ppm. 13C NMR 8.15–8.14 (m, 2 H), 7.52–7.49 (m, 1 H), 7.47–7.44 (m, 2 H), 7.21 (d,
(125 MHz, CDCl3): δ = 164.9 (d, J = 250.4 Hz) 156.7, 139.5, 130.2 (d,
J = 7.9 Hz, 1 H), 7.13 (d, J = 7.8 Hz, 1 H), 6.84 (s, 1 H), 5.37 (s, 2 H),
J = 8.9 Hz), 129.0, 128.5 (d, J = 2.4 Hz), 126.5, 124.6, 123.7, 122.1, 2.36 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 157.0, 137.2, 136.4,
115.2 (d, J = 21.7 Hz), 66.5 ppm. MS (EI): m/z (%) = 226.70 (72) [M]+,
94.87 (100).
132.5, 131.2, 129.5, 128.2, 127.9, 124.5, 124.3, 122.1, 66.5, 21.2 ppm.
MS (EI): m/z (%) = 223.03 (18) [M]+, 77.07 (100).
2-[4-(Trifluoromethyl)phenyl]-4H-benzo[d][1,3]oxazine
(4m):
6-Methyl-2-p-tolyl-4H-benzo[d][1,3]oxazine (4u): Yield: 431.9 mg,
91 %. White solid; m.p. 144–145 °C. H NMR (500 MHz, CDCl3): δ =
Yield: 504.1 mg, 91 %. White solid; m.p. 150–152 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.26 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.3 Hz,
2 H), 7.36–7.31 (m, 2 H), 7.24–7.21 (m, 1 H), 7.04 (d, J = 7.4 Hz, 1 H),
5.44 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 156.2, 139.2, 135.8,
132.9 (q, J = 97.5 Hz), 129.2, 128.2, 127.1, 125.2 (q, J = 11.2 Hz),
124.9, 123.8, 122.8, 122.1, 66.6 ppm. ESI-HRMS: m/z calcd. for
C15H10F3NO + H+ 278.0787; found 278.0794.
1
8.03 (d, J = 8.2 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 2 H), 7.20 (d, J = 7.9 Hz,
1 H), 7.12 (d, J = 7.8 Hz, 1 H), 6.83 (s, 1 H), 5.35 (s, 2 H), 2.42 (s, 3
H), 2.36 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 157.3, 141.8,
137.2, 126.2, 129.6, 129.5, 129.0, 127.9, 124.3, 124.2, 122.1, 66.4, 21.6,
21.2 ppm. MS (EI): m/z (%) = 237.17 (26) [M]+, 91.09 (100).
2-(4-Bromophenyl)-6-methyl-4H-benzo[d][1,3]oxazine
(4v):
Yield: 562.0 mg, 93 %. White solid; m.p. 188–190 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.01 (d, J = 8.5 Hz, 2 H), 7.58 (d, J = 8.6 Hz,
2 H), 7.20 (d, J = 7.9 Hz, 1 H), 7.13 (d, J = 7.8 Hz, 1 H), 6.84 (s, 1 H),
5.37 (s, 2 H), 2.36 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 156.2,
136.8, 136.7, 131.5, 131.4, 129.6, 129.4, 126.0, 124.5, 124.4, 121.9,
66.6, 21.2 ppm. ESI-HRMS: m/z calcd. for C15H12BrNO + H+ 302.0175;
found 302.0182.
2-(Furan-2-yl)-4a,8a-dihydro-4H-benzo[d][1,3]oxazine
(4n):
Yield: 298.8 mg, 75 %. Yellow solid; m.p. 63–64 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.60–7.59 (m, 1 H), 7.34–7.31 (m, 2 H), 7.30–
7.28 (m, 1 H), 7.18–7.15 (m, 1 H), 7.06–6.97 (m, 1 H), 6.52–6.51 (m,
1 H), 5.33 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 150.4, 146.3,
145.5, 138.9, 129.1, 126.5, 124.7, 123.7, 122.1, 114.8, 111.8, 66.3 ppm.
MS (EI): m/z (%) = 198.89 (98) [M]+, 94.97 (100).
2-(Thiophen-2-yl)-4a,8a-dihydro-4H-benzo[d][1,3]oxazine (4o):
Yield: 400.4 mg, 93 %. Yellow oil. 1H NMR (500 MHz, CDCl3): δ =
7.76–7.75 (m, 1 H), 7.51–7.49 (m, 1 H), 7.33–7.30 (m, 1 H), 7.28–7.27
(m, 1 H), 7.20–7.16 (m, 1 H), 7.13–7.11 (m, 1 H), 7.01 (d, J = 7.3 Hz,
1 H), 5.37 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 154.2, 139.5,
136.6, 130.3, 130.0, 129.0, 127.7, 126.3, 124.4, 123.7, 122.1, 66.6 ppm.
ESI-HRMS: m/z calcd. for C12H9NOS + H+ 216.0478; found 216.0479.
6-Methoxy-2-phenyl-4H-benzo[d][1,3]oxazine
(4w):
Yield:
449.8 mg, 94 %. White solid; m.p. 109–111 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.14–8.12 (m, 2 H), 7.46–7.44 (m, 3 H), 7.26–7.24 (m, 1
H), 6.86–6.84 (m, 1 H), 6.56 (d, J = 2.7 Hz, 1 H), 5.37 (s, 2 H), 3.82 (s,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.3, 155.8, 133.1, 132.5,
131.0, 128.2, 127.7, 125.9, 123.4, 113.6, 109.5, 66.3, 55.5 ppm. ESI-
HRMS: m/z calcd. for C15H13NO2 + H+ 240.1019; found 240.1018.
2-(5-Bromothiophen-2-yl)-4H-benzo[d][1,3]oxazine (4p): Yield:
441.2 mg, 75 %. White solid; m.p. 127–128 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.46 (d, J = 4.0 Hz, 1 H), 7.31 (t, J = 7.4 Hz, 1 H), 7.23 (d,
J = 7.5 Hz, 1 H), 7.18–7.17 (m, 1 H), 7.07 (d, J = 4.0 Hz, 1 H), 7.00 (d,
J = 7.2 Hz, 1 H), 5.35 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
153.0, 139.3, 138.0, 130.8, 130.0, 129.1, 126.5, 124.5, 123.8, 122.0,
117.9, 66.8 ppm. ESI-HRMS: m/z calcd. for C12H8BrNOS + H+
293.9583; found 293.9588.
6-Methoxy-2-p-tolyl-4H-benzo[d][1,3]oxazine
(4x):
Yield:
410.3 mg, 81 %. White solid; m.p. 135–138 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.01 (d, J = 8.2 Hz, 2 H), 7.28–7.23 (m, 3 H), 6.86–6.84
(m, 1 H), 6.56 (d, J = 2.7 Hz, 1 H), 5.35 (s, 2 H), 3.82 (s, 3 H), 2.42 (s,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.1, 156.1, 141.5, 133.2,
129.7, 129.0, 127.7, 125.7, 123.5, 113.6, 109.5, 66.3, 55.5, 21.5 ppm.
ESI-HRMS: m/z calcd. for C16H15NO2 + H+ 254.1176; found 254.1183.
2-(4-Fluorophenyl)-6-methoxy-4H-benzo[d][1,3]oxazine
(4y):
2-(Naphthalen-1-yl)-4H-benzo[d][1,3]oxazine
(4q):
Yield:
Yield: 422.0 mg, 82 %. White solid; m.p. 141–142 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.12–8.09 (m, 2 H), 7.22 (d, J = 8.6 Hz, 1 H),
7.10 (t, J = 8.7 Hz, 2 H), 6.84–6.82 (m, 1 H), 6.53 (d, J = 2.6 Hz, 1 H),
5.32 (s, 2 H), 3.80 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.6
(d, J = 252.4 Hz), 158.2, 154.8, 132.8, 129.8 (d, J = 9.1 Hz), 128.6 (d,
J = 2.9 Hz), 125.7, 123.2, 115.1 (d, J = 21.5 Hz), 113.6, 109.4, 66.3, 55.4
ppm. ESI-HRMS: m/z calcd. for C15H12FNO2 + H+ 258.0925; found
258.0930.
409.7 mg, 79 %. White solid; m.p. 60–61 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.89 (d, J = 8.6 Hz, 1 H), 8.09–8.08 (m, 1 H), 7.99 (d, J =
8.2 Hz, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.64–7.61 (m, 1 H), 7.57–7.53
(m, 2 H), 7.42–7.37 (m, 2 H), 7.28–7.25 (m, 1 H), 7.09 (d, J = 7.5 Hz,
1 H), 5.54 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.0, 139.5,
134.0, 131.7, 131.1, 130.0, 129.1, 128.9, 128.5, 127.1, 126.9, 126.1,
126.0, 124.8, 124.8, 123.8, 122.0, 66.6 ppm. ESI-HRMS: m/z calcd. for
C18H13NO + H+ 260.1070; found 260.1078.
6-Chloro-2-phenyl-4H-benzo[d][1,3]oxazine (4z): Yield: 394.8 mg,
81 %. White solid; m.p. 143–144 °C. H NMR (500 MHz, CDCl3): δ =
(E)-2-Styryl-4H-benzo[d][1,3]oxazine (4r): Yield: 428.2 mg, 91 %.
Pale yellow solid; m.p. 111–112 °C. 1H NMR (500 MHz, CDCl3): δ =
7.56–7.52 (m, 3 H), 7.42–7.36 (m, 3 H), 7.33–7.30 (m, 1 H), 7.26–7.24
(m, 1 H), 7.21–7.18 (m, 1 H), 7.02 (d, J = 7.3 Hz, 1 H), 6.72 (d, J =
16.0 Hz, 1 H), 5.35 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
158.1, 139.8, 139.0, 135.4, 129.5, 129.0, 128.8, 127.6, 126.6, 124.4,
123.7, 122.3, 121.5, 66.1 ppm. MS (EI): m/z (%) = 235.10 (64) [M]+,
234.02 (100).
1
8.15–8.12 (m, 2 H), 7.54–7.50 (m, 1 H), 7.47–7.44 (m, 2 H), 7.29–7.27
(m, 1 H), 7.23–7.16 (d, J = 8.2 Hz, 1 H), 7.02–7.01(m, 1 H), 5.36 (s, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 157.8, 138.3, 132.0, 131.7,
131.4, 129.0, 128.3, 128.0, 125.9, 123.9, 123.8, 65.9 ppm. MS (EI): m/z
(%) = 242.92 (18) [M]+, 77.06. (100).
2-Phenylquinazoline (6a): Yield: 400.0 mg, 97 %. Yellow solid; m.p.
100–101 °C. 1H NMR (500 MHz, CDCl3): δ = 9.48–9.47 (m, 1 H), 8.66–
8.64 (m, 2 H), 8.10 (d, J = 8.1 Hz, 1 H), 7.92–7.90 (m, 2 H), 7.61–7.51
(m, 4 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 161.0, 160.5, 150.7,
138.0, 134.1, 130.6, 128.6, 128.6, 127.2, 127.1, 123.6 ppm. MS (EI):
m/z (%) = 205.68 (90) [M]+, 179.09 (100).
2-Propyl-4H-benzo[d][1,3]oxazine (4s): Yield: 254.4 mg, 73 %.
Brown oil. 1H NMR (500 MHz, CDCl3): δ = 7.26 (t, J = 8.2 Hz, 1 H),
7.14 (t, J = 7.1 Hz, 2 H), 6.92 (d, J = 7.1 Hz, 1 H), 5.21 (s, 2 H), 2.34
(t, J = 7.6 Hz, 2 H), 1.77–1.70 (m, 2 H), 1.01 (t, J = 7.4 Hz, 3 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 163.7, 138.9, 128.8, 126.0, 123.8,
123.5, 121.7, 65.8, 36.9, 19.8, 13.7 ppm. MS (EI): m/z (%) = 175.10
(20) [M]+, 119.17 (100).
2-o-Tolylquinazoline (6b): Yield: 400.0 mg, 91 %. Pale yellow solid;
m.p. 44–45 °C, 1H NMR (500 MHz, CDCl3): δ = 9.52 (s, 1 H), 8.12–
8.10 (m, 1 H), 7.98–7.91 (m, 3 H), 7.69–7.66 (m, 1 H), 7.39–7.34 (m,
3 H), 3.08 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.0, 160.1,
6-Methyl-2-phenyl-4H-benzo[d][1,3]oxazine (4t): Yield: 384.0 mg,
1
86 %. White solid; m.p. 101–103 °C. H NMR (500 MHz, CDCl3): δ =
Eur. J. Org. Chem. 2017, 3335–3342
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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150.4, 138.6, 137.4, 134.1, 131.3, 130.6, 129.3, 128.6, 127.5, 127.0, 1 H), 7.42–7.41 (m, 1 H), 6.85–6.57 (m, 1 H) ppm. 13C NMR (125 MHz,
126.0, 122.9, 21.0 ppm. MS (EI): m/z (%) = 220.14 (68) [M]+, 219.04
(100).
CDCl3): δ = 160.6, 154.0, 152.4, 150.3, 145.2, 134.4, 128.2, 127.1,
123.2, 114.0, 112.2 ppm. MS (EI): m/z (%) = 196.04 (94) [M]+, 76.04
(100).
2-m-Tolylquinazoline (6c): Yield: 410.0 mg, 93 %. White solid; m.p.
1
2-(Thiophen-2-yl)quinazoline (6l): Yield: 390.6 mg, 92 %. White
101–102 °C. H NMR (500 MHz, CDCl3): δ = 9.48 (s, 1 H), 8.44 (t, J =
1
solid; m.p. 134–135 °C. H NMR (500 MHz, CDCl3): δ = 9.35 (s, 1 H),
6.9 Hz, 2 H), 8.10 (t, J = 4.4 Hz, 1 H), 7.95–7.91 (m, 2 H), 7.64–7.61
(m, 1 H), 7.45 (t, J = 3.8 Hz, 1 H), 7.35 (d, J = 7.6 Hz, 1 H), 2.51 (s, 3
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 161.3, 160.5, 150.8, 138.3,
138.0, 134.1, 131.4, 129.1, 128.6, 128.6, 127.2, 127.1, 125.8, 123.6,
21.5 ppm. MS (EI): m/z (%) = 220.18 (100) [M]+.
8.17–8.16 (m, 1 H), 8.02–8.00 (m, 1 H), 7.89–7.86 (m, 2 H), 7.58–7.52
(m, 2 H), 7.21–7.20 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
160.5, 157.8, 150.6, 143.8, 134.3, 129.9, 129.2, 128.3, 128.2, 127.2,
127.0, 123.3 ppm. MS (EI): m/z (%) = 211.91 (90) [M]+, 76.04 (100).
2-(Pyridin-3-yl)quinazoline (6m): Yield: 381.2 mg, 92 %. White
solid; m.p. 93–95 °C. H NMR (500 MHz, CDCl3): δ = 9.81–9.80 (m, 1
2-p-Tolylquinazoline (6d): Yield: 418.2 mg, 95 %. Pale yellow solid;
m.p. 104–106 °C. H NMR (500 MHz, CDCl3): δ = 9.47 (s, 1 H), 8.54–
1
1
H), 9.46 (s, 1 H), 8.87–8.84 (m, 1 H), 8.74–8.73 (m, 1 H), 8.09–8.08
(m, 1 H), 7.94–7.91 (m, 2 H), 7.66–7.63 (m, 1 H), 7.46–7.43 (m, 1 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 160.6, 159.2, 151.2, 150.6,
150.3, 135.7, 134.4, 133.5, 128.6, 127.7, 127.2, 123.8, 123.4 ppm. MS
(EI): m/z (%) = 206.92 (60) [M]+, 75.96 (100).
8.52 (m, 2 H), 8.09–8.08 (m, 1 H), 7.93–7.89 (m, 2 H), 7.62–7.59 (m,
1 H), 7.37 (d, J = 8.0 Hz, 2 H), 2.47 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 161.2, 160.4, 150.8, 140.8, 135.3, 134.0, 129.4, 128.6,
128.5, 127.1, 127.0, 123.5, 21.5 ppm. MS (EI): m/z (%) = 220.12 (100)
[M]+.
2-(Naphthalen-1-yl)quinazoline (6n): Yield: 461.3 mg, 90 %. Pale
yellow solid; m.p. 124–125 °C. 1H NMR (500 MHz, CDCl3): δ = 9.61
(s, 1 H), 8.72 (d, J = 8.1 Hz, 1 H), 8.20 (d, J = 8.0 Hz, 2 H), 8.03–7.95
(m, 4 H), 7.72–7.69 (m, 1 H), 7.67–7.64 (m, 1 H), 7.59–7.54 (m, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 163.5, 160.4, 150.6, 136.3,
134.3, 134.2, 131.2, 130.4, 129.6, 128.7, 128.5, 127.7, 127.1, 126.9,
125.9, 125.9, 125.3, 123.1 ppm. MS (EI): m/z (%) = 256.14 (80) [M]+,
255.05 (100).
2-Propylquinazoline (6o): Yield: 296.2 mg, 86 %. Yellow oil. 1H
NMR (500 MHz, CDCl3): δ = 9.27 (s, 1 H), 7.91 (d, J = 9.2 Hz, 1 H),
7.81–7.78 (m, 2 H), 7.52–7.49 (m, 1 H), 3.06–3.03 (m, 2 H), 1.94–1.86
(m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 167.5, 160.2, 150.2, 133.8, 127.7, 126.9, 126.7, 122.9, 41.7, 22.1,
13.8 ppm. MS (EI): m/z (%) = 172.08 (46) [M]+, 143.91 (100).
2-(4-Methoxyphenyl)quinazoline (6e): Yield: 430.0 mg, 91 %.
White solid; m.p. 91–92 °C. H NMR (500 MHz, CDCl3): δ = 9.42 (s, 1
1
H), 8.61–8.58 (m, 2 H), 8.06–8.04 (m, 1 H), 7.90–7.87 (m, 2 H), 7.59–
7.56 (m, 1 H), 7.08–7.05 (m, 2 H), 3.91 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 161.8, 160.9, 160.4, 150.8, 134.0, 130.7, 130.2,
128.4, 127.1, 126.8, 123.3, 114.0, 55.4 ppm. MS (EI): m/z (%) = 236.05
(100) [M]+.
2-(2-Bromophenyl)quinazoline (6f): Yield: 532.6 mg, 95 %. Pale
1
yellow oil. H NMR (500 MHz, CDCl3): δ = 9.47 (s, 1 H), 8.08 (d, J =
8.1 Hz, 1 H), 7.90–7.86 (m, 2 H), 7.78–7.76 (m, 1 H), 7.70–7.68 (m, 1
H), 7.62–7.59 (m, 1 H), 7.43–7.39 (m, 1 H), 7.28–7.25 (m, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 162.5, 160.0, 150.0, 140.0, 134.2,
133.5, 131.5, 130.2, 128.3, 127.8, 127.2, 126.9, 123.0, 121.7 ppm. MS
(EI): m/z (%) = 284.07 (20) [M]+, 205.13 (100).
1
2-Decylquinazoline (6p): Yield: 517.3 mg, 96 %. Pale yellow oil. H
2-(3-Bromophenyl)quinazoline (6g): Yield: 512.0 mg, 91 %. White
NMR (500 MHz, CDCl3): δ = 9.26 (s, 1 H), 7.90 (d, J = 8.3 Hz, 1 H),
7.79–7.76 (m, 2 H), 7.50–7.47 (m, 1 H), 3.05 (t, J = 7.8 Hz, 2 H), 1.89–
1.83 (m, 2 H), 1.40–1.17 (m, 14 H), 0.79 (t, J = 7.0 Hz, 3 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 167.8, 160.2, 150.2, 133.8, 127.8, 126.9,
122.9, 39.9, 31.8, 29.4, 29.4, 29.3, 22.5, 14.0 ppm. ESI-HRMS: m/z
calcd. for C18 H26 N2 + H+ 271.2169; found 271.2165.
1
solid; m.p. 149–150 °C. H NMR (500 MHz, CDCl3): δ = 9.48 (s, 1 H),
8.81 (t, J = 1.8 Hz, 1 H), 8.59–8.56 (m, 1 H), 8.12–8.10 (m, 1 H), 7.96–
7.93 (m, 2 H), 7.68–7.63 (m, 2 H), 7.42 (t, J = 7.9 Hz, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 160.6, 159.6, 150.7, 140.1, 134.3, 133.5,
131.6, 130.1, 128.7, 127.7, 127.2, 127.1, 123.8, 123.0 ppm. MS (EI):
m/z (%) = 283.94 (80) [M]+, 102.18 (100).
2-Phenethylquinazoline (6q): Yield: 388.9 mg, 83 %. Yellow solid;
2-(4-Bromophenyl)quinazoline (6h): Yield: 507.5 mg, 89 %. White
1
m.p. 44–45 °C. H NMR (500 MHz, CDCl3): δ = 9.38 (s, 1 H), 8.01 (d,
1
solid; m.p. 137–138 °C. H NMR (500 MHz, CDCl3): δ = 9.38 (s, 1 H),
J = 8.8 Hz, 1 H), 7.92–7.88 (m, 2 H), 7.63–7.60 (m, 1 H), 7.34–7.28
(m, 4 H), 7.22–7.19 (m, 1 H), 3.49–3.45 (m, 2 H), 3.30–3.27 (m, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 166.7, 160.4, 150.3, 141.5,
134.0, 128.4, 128.3, 127.9, 127.0, 127.0, 125.9, 123.1, 41.5, 34.8 ppm.
MS (EI): m/z (%) = 234.08 (94) [M]+, 91.02 (100).
8.47–8.45 (m, 2 H), 8.03–8.01 (m, 1 H), 7.88–7.85 (m, 2 H), 7.63–7.61
(m, 2 H), 7.59–7.56 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
160.4, 160.0, 150.6, 136.9, 134.2, 131.7, 130.1, 128.5, 127.4, 127.1,
125.3, 123.6 ppm. MS (EI): m/z (%) = 283.93 (40) [M]+, 75.95 (100).
2-(4-Fluorophenyl)quinazoline (6i): Yield: 421.5 mg, 94 %. White
solid; m.p. 132–133 °C. H NMR (500 MHz, CDCl3): δ = 9.42 (s, 1 H),
2-[1-(Benzo[d][1,3]dioxol-5-yl)propan-2-yl]quinazoline
(6r):
1
Yield: 528.5 mg, 90 %. Pale yellow oil. 1H NMR (500 MHz, CDCl3):
δ = 9.25 (s, 1 H), 7.91–7.89 (m, 1 H), 7.74–7.70 (m, 2 H), 7.44–7.41
(m, 1 H), 6.67 (s, 1 H), 6.58 (d, J = 0.6 Hz, 2 H), 5.75 (s, 2 H), 3.50–
3.43 (m, 1 H), 3.27–3.22 (m, 1 H), 2.87–2.83 (m, 1 H), 1.35 (d, J =
6.9 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 170.1, 160.1, 150.0,
147.1, 145.4, 134.1, 133.5, 127.7, 126.7, 126.6, 123.0, 121.7, 109.3,
107.7, 100.3, 45.2, 41.6, 19.3 ppm. ESI-HRMS: m/z calcd. for C18 H16
N2 O2 + H+ 293.1285; found 293.1283.
8.65–8.61 (m, 2 H), 8.07–8.05 (m, 1 H), 8.05–7.88 (m, 2 H), 7.61–7.58
(m, 1 H), 7.24–7.19 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
164.6 (d, J = 249.2 Hz), 160.4, 160.0, 150.7, 134.2 (d, J = 2.4 Hz),
134.1, 130.6 (d, J = 8.1 Hz), 128.5, 127.2, 127.1, 123.4, 115.5 (d, J =
21.6 Hz) ppm. MS (EI): m/z (%) = 224.05 (100) [M]+.
2-(4-Nitrophenyl)quinazoline (6j): Yield: 457.2 mg, 91 %. Yellow
1
solid; m.p. 218–219 °C. H NMR (500 MHz, CDCl3): δ = 9.53 (s, 1 H),
8.84–8.81 (m, 2 H), 8.40–8.37 (m, 2 H), 8.15–8.14 (m, 1 H), 8.01–7.97
(m, 2 H), 7.73–7.70 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
160.7, 158.8, 150.6, 149.2, 143.8, 134.6, 129.4, 128.9, 128.3, 127.2,
123.9, 123.8 ppm. MS (EI): m/z (%) = 250.98 (40) [M]+, 76.05 (100).
2-tert-Butylquinazoline (6s): Yield: 324.0 mg, 87 %. Pale yellow oil.
1H NMR (500 MHz, CDCl3): δ = 9.36 (s, 1 H), 8.00 (d, J = 8.5 Hz, 1 H),
7.87–7.83 (m, 2 H), 7.58–7.55 (m, 1 H), 1.53 (s, 9 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 173.5, 159.9, 150.1, 133.5, 128.4, 126.8, 126.7,
122.8, 39.5, 29.6 ppm. MS (EI): m/z (%) = 186.05 (100) [M]+.
2-(Furan-2-yl)quinazoline (6k): Yield: 349.2 mg, 89 %. Yellow solid;
1
m.p. 127–129 °C. H NMR (500 MHz, CDCl3): δ = 9.31 (s, 1 H), 8.05–
6-Methoxy-2-phenylquinazoline (6t): Yield: 392.1 mg, 83 %. Yel-
1
8.03 (m, 1 H), 7.85–7.81 (m, 2 H), 7.66–7.65 (m, 1 H), 7.54–7.51 (m,
low solid; m.p. 119–120 °C. H NMR (500 MHz, CDCl3): δ = 9.38 (s,
Eur. J. Org. Chem. 2017, 3335–3342
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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1 H), 8.59–8.57 (m, 2 H), 8.01 (d, J = 9.2 Hz, 1 H), 7.58–7.49 (m, 4 H),
7.17 (d, J = 2.8 Hz, 1 H), 3.98 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 159.4, 158.8, 158.3, 147.0, 138.2, 130.2, 130.2, 128.6,
128.2, 127.2, 124.5, 103.9, 55.7 ppm. MS (EI): m/z (%) = 236.07 (100)
[M]+.
6-Chloro-2-(4-methoxyphenyl)quinazoline (6u): Yield: 438.5 mg,
1
81 %. White solid; m.p. 165–166 °C. H NMR (500 MHz, CDCl3): δ =
9.34 (s, 1 H), 8.57–8.54 (m, 2 H), 7.98 (d, J = 8.9 Hz, 1 H), 7.86 (d, J =
2.2 Hz, 1 H), 7.81–7.79 (m, 1 H), 7.06–7.03 (m, 2 H), 3.91 (s, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 162.0, 161.1, 159.4, 149.3,
134.9, 132.2, 130.3, 130.2, 130.1, 125.8, 123.7, 114.0, 55.4 ppm. MS
(EI): m/z (%) = 270.01 (100) [M]+.
Azabicyclo[3.3.1]nonane N-Hydroxide (ABNOH): 1H NMR
(500 MHz, CDCl3): δ = 3.20 (s, 2 H), 2.40–2.36 (m, 2 H), 2.06–2.02 (m,
2 H), 1.93–1.79 (m, 4 H), 1.62–1.59 (m, 1 H), 1.48–1.43 (m, 1 H), 1.35–
1.31 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 55.9, 31.7, 22.1,
19.7, 19.3 ppm.
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Keywords: Nitrogen heterocycles · Oxygen heterocycles ·
Radical reactions · 4H-3,1-Benzoxazines · Quinazolines ·
Oxidation · Oxygen
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Received: March 16, 2017
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