Iodine-catalyzed, stereo- and regioselective synthesis of 4-arylidine-4H-benzo[d][1,3]oxazines and their applications for the synthesis of quinazoline 3-oxides

Article abstract of DOI:10.1002/adsc.201200018

4-Benzylidene-2-aryl-4H-benzo[d][1,3] oxazines have been synthesized with high stereoselectivity and regioselectivities from 2-alkynylbenzamides in the presence of a catalytic amount of I₂. In the reaction mechanism, iodine plays a key role in

Full text of DOI:10.1002/adsc.201200018

FULL PAPERS
DOI: 10.1002/adsc.201200018
Iodine-Catalyzed, Stereo- and Regioselective Synthesis of
4-Arylidine-4H-benzo[d][1,3]oxazines and their Applications for
G
the Synthesis of Quinazoline 3-Oxides
Wen-Chun Lee,a Ho-Chuan Shen,a Wan-Ping Hu,b Wei-Sheng Lo,a
Chebrolu Murali,a Jaya Kishore Vandavasi,a and Jeh-Jeng Wanga,*
a
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
E-mail: jjwang@kmu.edu.tw
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung City, Taiwan
b
Received: January 6, 2012; Revised: March 21, 2012; Published online: && &&, 0000
Abstract: 4-Benzylidene-2-aryl-4H-benzo[d]ACTHNUGRTENUNG[1,3] ox- cilitate catalyst recovery. The benzoxazines have
azines have been synthesized with high stereoselec- been exploited as potential substrates for the synthe-
tivity and regioselectivities from 2-alkynylbenz- sis of quinazoline 3-oxide derivatives directly in one
ACHTUNGTRENNUNGamides in the presence of a catalytic amount of I2. In step.
the reaction mechanism, iodine plays a key role in
two different aspects as a catalyst, such as to activate
the alkyne with the iodinium donor which triggers Keywords: 6-exo-dig cyclization; iodine; quinazoline
the cascade, and then as a proper acid source to fa- 3-oxides; regioselectivity; stereoselectivity
Introduction
heterocyclic molecules from the corresponding alkyn-
yl precursors.
Benzoxazines and their analogues are a significant
In recent years, gold and platinum complexes have
class of heterocycles exhibiting various biological attracted keen interest of organic chemists by activat-
properties such as inhibitory activity towards human ing the alkyne, where the alkyne activation partici-
leukocyte elastase[1] and Clr serine protease en- pates in important molecular transformations, such as
zymes.[2] Numerous benzoxazine analogues were cyclization, cycloisomerization, cycloaddition, etc.[9i]
evolved as DNA-binding antitumor agents[3] and also Generally, transition metal-mediated cyclizations of 2-
act as progesterone receptor modulators.[4] Several alkynylamide A may take place via two possible
polymeric benzoxazines were explored as heat resist- modes of cyclizations. viz., 6-exo-dig A1[14] or 5-endo-
ant and electronic materials.[5] As a consequence of dig A2[14] modes as mentioned in Figure 1. It was
this characteristic behaviour of benzoxazine ana- found that 1-(o-alkynylaryl)ureas are convenient sub-
logues, new methodologies and synthetic routes have strates that provide an adequate framework to ex-
been developed in the recent past.[6–8] However, these plore the Au(I)-catalyzed hydroamidation of alkynes
methodologies require much attention to improve the to synthesize 6-exo-dig compounds.[14b] Synthesis of in-
scope and applicability for the synthesis of a wide doles by the 5-endo-dig mode from o-iodotrifluoro-
range of benzoxazines. Certain cyclization reactions
ACHTUNGTRENaNGNU cetanilide and 1-alkynes in the presence of copper
of various alkynyl derivatives by metal- and non- catalyst was also reported by Cacchi et al.[14c] Annula-
metal-mediated methodologies were developed with
different functionally substituted ortho-alkynyl sub-
strates having proximity of the reacting functional
groups within the molecule that facilitate the intramo-
lecular cyclizations.[9–12] In particular, I2,[13a] its perti-
nent reagents[9–11] and metal halide[11] mediated cycli-
zations were developed to synthesize various oxygen
heterocycles. All these methodologies have their own
distinct applicability for the construction of various
Figure 1. Two possible cyclized intermediates of A by metal
catalysis.
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tion of o-alkynylaniline derivatives represents a well-
authorized route to indole rings via a highly favored
5-endo-dig method,[15] whereas in our case we ob-
served specifically the 6-exo-dig product without any
side product such as indole derivatives. We have ob-
tained exclusively the 6-exo-dig derivatives compared
to the other reports regarding the annulation. A vast
number of reports was aimed to synthesis the indole
derivatives with the N-substituent on compound
3.[16–18]
Very recently, Saito et al. reported[14] a regio- and
stereoselective synthesis of 4-alkylidene-3,1-benzoxa-
zines via the 6-exo-dig mode of cyclization of N-acyl-
ACHTUNGTRENNUNGalkynylanilines. Although this method emphasized the
stereo- and regioselectivities of cyclization, the utiliza-
tion of equimolar amounts of acid under reflux reac-
tion conditions and transition metal catalysts reveals
the dissimilarity in the approach towards the synthesis
of various benzoxazines shown in the present commu-
Scheme 1. Cyclization of 3 in the presence of I2 to obtain
benzoxazines 4.
nication. We have replaced the palladium with a cata- way (A1, Figure 1) during the construction of the ben-
lytic amount of iodine for the synthesis of benzoxa- zoxazines. The present observation is significant be-
zines with this new methodology. In addition, the syn- cause of the high regio- and stereoselectivity of the
thesized benzoxazines have been exploited as poten- benzoxazine product formation during this electro-
tial precursors for the synthesis of quinazoline 3- philic cyclization reaction. Initial optimization of the
oxides. These quinazoline 3-oxides were reported as reaction was performed in different solvents, from
excellent precursors for the construction of various which the toluene is found to be of best solvent
heterocycles of biological importance[19] and the syn- system (Table 1, entry 7). The reaction was further op-
thesis of such derivatives was executed from the cor- timized with different quantities of I2 with 3a and the
responding amidoximes by the cyclization method.[19]
results are summarized in Table 1. The initial reaction
Molecular iodine in organic synthesis has been with 1.0 equiv. of I2 resulted in an 89% yield of the
known for a long time. In recent years, molecular desired product.
iodine has attracted considerable attention as a non-
Furthermore, the reaction was carried out by vary-
toxic, inexpensive, readily available catalyst for vari- ing the amount of I2. Among the four different reac-
ous organic conversions under mild and adaptable tion conditions used with 3a (entries 7, 10–12), a good
conditions to furnish the corresponding products in yield of the cyclized product is obtained in the pres-
excellent yields with high selectivity. Mostly, iodine- ence of 10 mol% of I2 in toluene at reflux tempera-
catalyzed transformations are based on heteroatom ture for 3 days (entry 7).
rather than carbophilic activation. However, there is
With these preliminary optimized reaction condi-
no example of benzoxazine synthesis using molecular tions in hand we further explored the scope and limi-
iodine as a catalyst.[13]
tations of the cyclization with different examples of
the various alkynyl amides and the results are sum-
marized in Table 2. Substrates bearing different func-
tional group combinations as the R1, R2 and R3 posi-
tions in 3 have been screened to evaluate the synthet-
Results and Discussion
Herein, we report an expedient I2-catalyzed cycliza- ic feasibility for the product formation (entries 1–20).
tion approach for the synthesis of benzoxazines 4 and Good to excellent yields were obtained in majority of
their applications for the synthesis of the quinazoline the cases except for compounds 4e and 4f. The pres-
3-oxides directly in one step. When alkynylamide 3 ence of the aromatic alkyne is desirable to promote
(prepared from 1 and 2) reacted with 10 mol% iodine the cyclization which was verified further by choosing
in toluene solvent at reflux temperature, it underwent some substrates having trimethylsilylacetyl
a cyclization to furnish an unexpected product, the nal acetylenes and alkyl groups at the R3 position (en-
benzoxazine 4 (Scheme 1).
tries 16–18): with the butyl group at the R3 position
ACHTUNGTRENUNeNG ne, termi-
We applied this methodology for the synthesis of the reaction did not suceed and led to the formation
differentially substituted 4-benzylidene-4H-benzo[d]- of compound 4-CP (entry 18). When the phenyl sub-
ACHTUNGTRENNUNG[1,3]oxazines from various substituted 2-alkylidene- stituent was replaced with an aliphatic group such as
benzamides. In the present context, the 6-exo-dig vinylbenzene or ethyl chain at the amide position the
mode of cyclization is observed as predominant path- desired product was obtained in a minor quantity and
2
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Iodine-Catalyzed, Stereo- and Regioselective Synthesis of 4-Arylidine-4H-benzo[d]ACTHNUTRGNE[NUG 1,3]oxazines
Table 1. Optimization of the reaction conditions for the cy-
ACHTUNGTRENNUNG
clization of compound 3 to 4.[a]
Table 2. Cyclization of various alkynylamides 3 in the pres-
ence of I2 as catalyst[a]
Entry
3
R1
R2
R3
4
Yield [%]
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
H
H
H
H
H
H
H
F
Cl
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
95
71
73
NO2 Ph
77
CF3
CH3
H
Ph
Ph
Ph
Ph
Ph
p-FC6H4
54[c]
46[c]
76
Entry
Solvent
I2 (equiv.)
4 [%]
4-CP [%]
CF3
CF3
CF3 Cl
CF3 Cl
1
2
3
MeCN
THF
DMF
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
1.0 equiv.
30 mol%
1.0 equiv.
30 mol%
5.0 equiv.
0
100
0
F
88
73
trace
18
65
0
22
95
60
61
89
90
92
9
72
24
15
75
0
14
20
0
10
11
12
13
14
15
16
17
18
19
20
71
76[b]
70
4
CH2Cl2
MeOH
DMSO
toluene
CH2Cl2
CH2Cl2
toluene
toluene
toluene
H
H
H
H
H
H
H
H
H
H
NO2 p-FC6H4
Cl
CF3
H
NO2 P-EtC6H4 4o
NO2 TMS
5[b]
6
p-FC6H4
p-FC6H4
p-FC6H4
65[b]
92
7
8[c]
9[d]
10[c]
11[d]
12
65
4p[d]
H
H
H
butyl
Ph
4q[e]
4r[f]
4s
0
0
[g]
3s
3t
–
–
20
20
[h]
Ph
4t
[a]
Reflux for 3 days.
Unreacted 3.
Reaction time 1 day.
[b]
[c]
[d]
[a]
Reaction conditions: Compound
3
(1.0 mmol), I2
(10 mol%), dry toluene (10.0 mL), reflux for 3 days.
1.0 equiv. of I2 was used.
Reaction time: 5 days.
Complex mixture of products.
[b]
[c]
[d]
[e]
[f]
Reaction time 2 days.
No reaction.
the major product was compound 4-CP. (entries 19
and 20). The stereochemistry of the cyclized product
was confirmed by the NOESY analysis of the majority
of the compounds 4 (see Supporting Information for
details). Structure of the product 4a is evidenced by
a single crystal X-ray analysis (Figure 2).
Compound 4-CP was observed.
Phenyl substituent replaced with vinylbenzene.
Phenyl substituent replaced with an ethyl chain.
[g]
[h]
could be quenched by the base to pause the reaction
The plausible mechanism for the formation of the at the iodide intermediate stage. Furthermore, the iso-
benzoxazines 4a is depicted in Scheme 2. The initially lated compound 6 was treated with 1.0 equiv. HI at
formed iodo complex 5 undergoes the electrophilic 08C for 3 h to obtain 4a (70% yield).
cyclization leading to the formation of intermediate 6
These control experiments evidently support the
which, in turn, reacts with in situ generated HI to fur- formation of HI during the reaction but its presence
nish the benzoxazine 4a with retention of the Z-ste- alone cannot play a role in the direct conversion of 3a
reochemistry along with the regeneration of I2. We to 4a. The compound 3a was found to be unchanged
also carried out the reaction of compound 3a with after heating in toluene without I2 under reflux condi-
10 mol% HI but the reaction did not progress to the tions. This experiment was performed to rule out the
formation of 4a. In order to check the possible forma- possibility of lingering traces of the metal[20] along
tion of the intermediate 6 and HI during the reaction, with the substrates that were prepared by using transi-
compound 3a was reacted with 10 mol% I2 along with tion metal catalysts.
the addition of NaHCO3 (3.0 equiv.) in toluene at
In the proposed mechanism, which is was well sup-
room temperature; this furnished the iodobenzoxa- ported by the experimental details, iodine participates
zine 6 as a sole product. Presumably, the formed HI in two different roles as a catalyst, first the iodonium
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Table 3. Synthesis of quinazoline 3-oxides 8 from benzoxa-
zines 5.[a]
Entry
4
R1
R2
R3
8
Yield [%]
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
H
H
H
H
H
H
CF3
CF3
CF3
CF3
H
H
H
H
H
H
F
Cl
NO2
CF3
Me
H
F
Cl
Cl
NO2
Cl
CF3
H
NO2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
75
77
68
79
86
66
83
81
36[b]
31
69
81
91
54
83
9
Ph
10
11
12
13
14
15
p-FC6H4
p-FC6H4
p-FC6H4
p-FC6H4
p-FC6H4
p-EtC6H4
Figure 2. ORTEP plot of 4a.
[a]
Reaction
conditions:
compound
4
(1.0 mmol),
NH2OH·HCl (1.0 mmol), methanol and dichloromethane
(10 mL, 4:1), and K2CO3 (1 mol%), room temperature
for 10 h.
[b]
Mixture of products formed.
H2O will generate the N-oxide. Biological studies of
the two N-oxides (8d and 8k) have shown the promis-
ing results. These two compounds were found to be
suitable for photodynamic therapy (PDT) applications
against melanoma as well as oral cancer cell lines[21]
(see see the Supporting Information for details).
Scheme 2. Plausible mechanism for the formation of benzox-
azine 4a.
Conclusions
In conclusion, we have developed a highly regio- and
donor activates the alkyne which triggers the cascade stereoselective synthesis of benzoxazines with catalyt-
and then as a proper acid source to facilitate catalyst ic I2. This novel method was able to replace the palla-
recovery. Thus, the I2-catalyzed cyclization of 3 dium with iodine to synthesize the benzoxazines. For
showed the synthetic feasibility for the formation of a long time there was a competition between the 5-
benzoxazines 4 and provided good yields in the range endo-dig and 6-exo-dig product formation and, even
of 46–95%.
though the previous reports furnish the 5-endo-dig
All benzoxazines with various substitutions have product with the 6-exo-dig product as a side product,
been converted to the quinazoline 3-oxides 8 with in our case we have been obtained the 6-exo-dig prod-
moderate to good yields (Table 3). A plaussible mech- uct exclusively. To the best of our knowledge, the syn-
anism for this one-pot approach for the synthesis of thesis of benzoxazines in the presence of molecular
N-oxides 8 is depicted in the Scheme 3. Initial attack iodine as a catalyst is a novel pathway and this is the
of NH2OH on the sp2 carbon (C-1) of the oxazine fol- first example of its use for the synthesis of benzoxa-
lowed by the H+ transfer could result in ring opening zines. The proposed mechanism, which is well en-
to form intermediate 10. Subsequent cyclization of dorsed by the experimental details, shows that iodine
the N-hydroxyimidamide followed by elimination of has two different roles as catalyst, (i) alkyne activa-
4
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Iodine-Catalyzed, Stereo- and Regioselective Synthesis of 4-Arylidine-4H-benzo[d]ACTHNUTRGNE[NUG 1,3]oxazines
Scheme 3. Plausible mechanism for the formation of quinazoline 3-oxides 8.
tion by the iodonium donor that triggers the cascade dry THF (5 mL) and charged with triethylamine (ca. 10 mL)
in a flask under an argon atmosphere. The reaction mixture
was stirred for 4 h and the reaction was monitered by TLC
analysis. The formed product was extracted with ethyl ace-
tate by washing with water, brine and followed by drying
over anhydrous Na2SO4. The organic layer was concentrated
under reduced pressure and the crude residue was chroma-
tographed over silica gel to obtain product.
N-[2-(Phenylethynyl)phenyl]benzamide (3a): The title
compound was prepared according to the general procedure
and purified by column chromatography to furnish a white
solid; yield: 90%; mp 103–1058C. 1H NMR (CDCl3,
400 MHz): d=8.96 (bs, 1H), 8.63 (d, J=8.4 Hz, 1H), 7.96
(d, J=8.0 Hz, 2H), 7.59–7.38 (m, 10H), 7.12 (td, J=8.0 and
1.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=165.1, 138.1,
134.9, 132.0, 131.5, 131.4, 129.9, 129.0, 128.9, 128.6, 126.9,
123.5, 122.2, 119.1, 112.2, 96.9, 84.4; HR-MS (ESI): m/z=
320.1048, calcd. for C21H15NONa: 320.1051; anal. calcd. for
C21H15NO: C 84.82, H 5.08, N 4.71; found: C 84.75, H 5.10,
N 4.70.
and then (ii) a proper acid source to facilitate the cat-
alyst recovery. Mostly, iodine-catalyzed transforma-
tions are based on heteroatom rather than carbophilic
activation.
It is noteworthy to mention that the benzoxazines
thus synthesized have been exploited as potential pre-
cursors for the efficient and one-pot synthesis of qui-
nazoline 3-oxides. Some compounds were found to be
suitable for photodynamic therapy (PDT) applications
against melanoma as well as oral cancer cell lines.
Further biological studies of the synthesized benzoxa-
zine molecules are in progress.
Experimental Section
General Procedure for the Synthesis of N-(2-Iodo-
aryl)amides 1a–1p
4-Fluoro-N-[2-(phenylethynyl)phenyl]benzamide
(3b):
Compounds 1a–1p were prepared and characterized accord-
ing to the modified literature procedure[1] as follows.
To an ice-cooled solution of the corresponding 2-iodoani-
line (1.0 mmol) and triethylamine (10 mL) in dry toluene
(10 mL) was added the corresponding benzoyl chloride
(1.5 mmol) and the reaction mixture was stirred under an
argon atmosphere for 6 h and reaction was monitored by
TLC analysis. The crude product was extracted with ethyl
acetate followed by washing with water and saturated
NaHCO3 solution and drying over anhydrous Na2SO4. The
organic layer was concentrated under reduced pressure and
the crude compound obtained was purified by column chro-
matography using ethyl acetate and hexane solvent system
to furnish amides 1a–1p.
The title compound was prepared according to the general
procedure and purified by column chromatography to afford
1
a white solid; yield: 75%; mp 134–1368C. H NMR (CDCl3,
400 MHz): d=8.86 (bs, 1H), 8.58 (d, J=8.4 Hz, 1H), 7.98–
7.93 (m. 2H), 7.55–7.50 (m, 3H), 7.43–7.38 (m, 4H), 7.18–
7.10 (m, 3H); 13C NMR (CDCl3, 100 MHz): d=166.3, 163.8
(d, J=29.9 Hz), 138.8, 131.5, 131.3, 131.1, 131.0 (d, J=
6.2 Hz), 129.3 (d, J=9.1 Hz), 129.1, 128.7, 123.6, 122.1,
119.1, 115.9 (d, J=22.0 Hz), 112.2, 97.0, 84.4; HR-MS (ESI):
m/z=338.0958, calcd. for C21H14FNONa: 338.0957; anal.
calcd. for C21H14FNO: C 79.98, H 4.47, N 4.44; found: C
79.72, H 4.52, N 4.40.
4-Chloro-N-[2-(phenylethynyl)phenyl]benzamide
(3c):
The title compound was prepared according to the general
procedure and purified by column chromatography to afford
1
a white solid; yield: 70%; mp 135–1378C. H NMR (CDCl3,
General Procedure for Synthesis of 2-Alkynylaryl-
amides 3a–3p
400 MHz): d=8.86 (bs, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.86
(d, J=8.8 Hz, 2H), 7.53–7.37 (m, 9H), 7.11 (td, J=8.0 and
1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz): d=163.8, 138.7,
138.3, 133.1, 131.4, 131.2, 129.8, 129.1, 129.0, 128.6, 128.3,
123.7, 122.0, 119.1, 112.2, 97.0, 84.3; HR-MS (ESI): m/z=
A
mixture of the corresponding iodo compound
1 (1.0 mmol), the corresponding terminal alkyne (1.5 mmol),
Pd(PPh3)4 (10 mol%) and CuI (10 mol%) was taken up in
ACHTUNGTRENNUNG
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354.0663, calcd. for C21H14ClNO (M+H)+: 354.0662; anal.
calcd. for C21H13ClNO: C 76.02, H 4.25, N 4.22; found: C
75.78, H 4.34, N 4.20.
100 MHz): d=166.5, 164.1 (d, J=10.6 Hz), 141.5, 131.5,
130.5 (d, J=3.1 Hz), 129.6, 129.5 (d, J=8.2 Hz), 128.8, 128.6
(q, J=3.8 Hz), 127.7, 126.7 (q, J=3.8 Hz), 125.7 (q, J=
33.4 Hz), 125.0, 123.3 (q, J=270.3 Hz), 122.3, 121.5, 118.9,
116.1 (d, J=22 Hz); HR-MS (ESI): m/z=384.1013, calcd.
for C22H14FNO: 384.1013; anal. calcd. for C22H13F4NO: C
68.93, H 3.42, N 3.65; found: C 68.87, H 3.42, N 3.68.
4-Nitro-N-[2-(phenylethynyl)phenyl]benzamide (3d): The
title compound was prepared according to the general pro-
cedure and purified by column chromatography to afford
a
yellow solid; yield: 87%; mp 160–1628C. 1H NMR
(CDCl3, 400 MHz): d=8.92 (bs, 1H), 8.58 (d, J=8.4 Hz,
1H), 8.32 (d, J=8.0 Hz, 2H), 8.11 (d, J=8.0 Hz, 2H), 7.57–
7.40 (m, 7H), 7.17 (t, J=8.4 Hz, 1H); 13C NMR (CDCl3,
100 MHz): d=162.8, 149.8, 140.3, 138.2, 131.7, 131.3, 129.9,
129.3, 128.8, 128.1, 124.3, 124.1, 121.8, 119.3, 112.6, 97.3,
4-Chloro-N-[2-(phenylethynyl)-4-(trifluoromethyl)phen-
yl]benzamide (3i): The title compound was prepared accord-
ing to the general procedure and purified by column chro-
matography to afford a white solid; yield: 66%; mp 178–
1
1808C. H NMR (CDCl3, 400 MHz): d=8.97
N
84.1;
HR-MS
(ESI):
m/z=365.0906,
calcd.
for
J=8.8 Hz, 1H), 7.88 (d, J=8.8 Hz, 2H), 7.80 (s, 1H), 7.64
(d, J=8.8 Hz, 1H), 7.56–7.53 (m, 2H), 7.48 (s, 1H), 7.46–
7.40 (m, 4H); 13C NMR (CDCl3, 100 MHz): d=164.0, 141.4,
138.9, 132.6, 131.5, 129.6, 129.3, 128.8, 128.6 (q, J=3.8 Hz),
126.7 (q, J=3.8 Hz), 125.7 (q, J=33.0 Hz), 123.5 (q, J=
270.0 Hz), 121.4, 118.9, 112.6, 98.3, 82.9; HR-MS (ESI):
m/z= 422.0537, calcd. for C22H13ClF3NONa: 422.0535; anal.
calcd. for C22H13ClF3NO: C 66.09, H 3.28, N 3.50; found: C
66.08, H 3.28, N 3.49.
C21H14N2O3Na: 365.0902; anal. calcd. for C21H14N2O3: C
73.68, H 4.12, N 8.18; found: C 73.15, H 4.16, N 8.12.
N-[2-(Phenylethynyl)phenyl]-4-(trifluoromethyl)benz-
amide (3e): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a white solid; yield: 88%; mp 153–1558C.
1H NMR (CDCl3, 400 MHz): d=8.92 (bs, 1H), 8.58 (d, J=
8.0 Hz, 1H), 8.05 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz,
2H), 7.56–7.38 (m, 7H), 7.14 (t, J=8.0 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): d=163.6, 138.5, 138.1, 133.7 (q, J=
33.0 Hz), 131.6, 131.3, 129.9, 129.2, 128.7, 127.4, 125.9 (q, J=
3.8 Hz), 124.0, 123.5 (q, J=270.0 Hz), 122.0, 119.3, 112.5,
97.2, 84.2; HR-MS (ESI): m/z=366.1104, calcd. for
C22H15F3NONa: 366.1106; anal. calcd. for C22H15F3NO: C
72.32, H 3.86, N 3.83; found: C 72.36, H 3.85, N 3.86.
4-Chloro-N-[2-(4-fluorophenylethynyl)-4-trifluoromethyl-
phenyl]benzamide (3j): The title compound was prepared
according to the general procedure and purified by column
chromatography to afford
a white solid; yield: 74%.
1H NMR (DMSO-d6, 400 MHz): d=10.35 (brs, 1H), 8.07–
7.97 (m, 4H), 7.81 (d, J=8.0 Hz), 7.71–7.55 (m, 4H), 7.29 (t,
J=8.0 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz): d=164.5,
142.3, 137.1, 133.9, 133.8 (d, J=8.3 Hz), 132.6, 129.7, 128.8
(d, J=18.2 Hz), 126.0, 125.3, 123.4 (q, J=268.5 Hz), 117.9
(d, J=2.9 Hz), 116.3, 116.1, 95.07, 84.6; HR-MS (ESI):
m/z=416.0484, calcd. for C22H12ClF4NO: 416.0478.
4-Methyl-N-[2-(phenylethynyl)phenyl]benzamide
The title compound was prepared according to the general
procedure and purified by column chromatography to afford
a yellow solid; yield: 78%. H NMR (CDCl3, 400 MHz): d=
(3f):
1
8.93 (brs, 1H), 8.62 (d, J=8.4 Hz, 1H), 7.87 (d, J=1.6 Hz,
2H), 7.57–7.52 (m, 3H), 7.43–7.38 (m, 4H), 7.27 (d, J=
8.0 Hz, 2H), 7.10 (dt, J=8.0 Hz, J=1.21 Hz, 1H), 2.42 (s,
3H); 13C NMR (CDCl3, 100 MHz): d=165.2, 142.6, 139.2,
132.0, 131.5, 131.4, 129.9, 129.5, 128.9, 128.6, 127.0, 123.4,
122.3, 119.1, 112.1, 96.9, 84.5, 21.5; HR-MS (ESI): m/z=
312.1390, calcd. for C22H17NO [(M+H)+]: 312.1383; anal.
calcd for C22H17NO: C 84.86, H 5.50, N 4.50; found: C 84.65,
H 5.55, N 4.48.
N-[2-(Phenylethynyl)-4-(trifluoromethyl)phenyl]benz-
amide (3g): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a white solid; yield: 81%; mp 127–1298C.
1H NMR (CDCl3, 400 MHz): d=9.04 (bs, 1H), 8.76 (d, J=
8.8 Hz, 1H), 7.95 (d, J=8.0 Hz, 2H), 7.78 (s, 1H), 7.63–7.37
(m, 9H); 13C NMR (CDCl3, 100 MHz): d=165.1, 141.6,
134.2, 132.4, 131.4, 129.4, 128.9, 128.7, 128.6, 128.5, 127.0,
126.6 (q, J=3.8 Hz), 125.5 (q, J=32.0 Hz), 123.0 (q, J=
270.0 Hz), 121.5, 118.8, 112.4, 98.2, 83.0; HR-MS (ESI):
m/z=338.0922, calcd. for C22H14F3NONa: 338.0925; anal.
calcd. for C22H14F3NO: C 72.32, H 3.86, N 3.83; found: C
72.59, H 4.04, N 3.75.
N-{2-[(4-Fluorophenyl)ethynyl]phenyl}-4-nitrobenzamide
(3k): The title compound was prepared according to the
general procedure and purified by column chromatography
to afford a yellow solid; yield: 83%; mp 176–1788C.
1H NMR (CDCl3, 400 MHz): d=8.84 (bs, 1H), 8.54 (d, J=
8.4 Hz, 1H), 8.32 (d, J=8.8 Hz, 2H), 8.08 (d, J=8.8 Hz,
2H), 7.67–7.41 (m, 4H), 7.16 (td, J=7.6 Hz and 1.2 Hz,
1H), 7.11 (t, J=8.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz):
d=164.2, 162.8, 161.7, 149.8, 140.2, 138.2, 133.3 (d, J=
8.4 Hz), 131.7, 130.0, 128.1, 124.3, 124.1, 119.4, 118.0, 117.9,
116.2 (d, J=22.1 Hz), 112.4, 96.1, 83.8; HR-MS (ESI): m/z=
361.0987, calcd. for C21H14FN2O3: 361.0988; anal. calcd. for
C21H13FN2O3: C 70.0, H 3.64, N 7.77; found: C 69.99, H 3.55,
N 7.73.
4-Chloro-N-{2-[(4fluorophenyl)ethynyl]phenyl}benzamide
(3l): The title compound was prepared according to the gen-
eral procedure and purified by column chromatography to
afford
a
white solid; yield: 82%. 1H NMR (CDCl3,
400 MHz): d=8.8 (brs, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.86
(d, J=8.4 Hz, 2H), 7.59–7.36 (m, 6H), 7.19–7.02 (m, 3H);
13C NMR (CDCl3, 100 MHz): d=164.0 (d, J=24.0 Hz),
161.7, 138.6 (d, J=34.1 Hz), 133.3 (d, J=9.1 Hz), 131.6,
130.0, 129.2, 128.3, 123.8, 119.3, 118.2, 116.1 (d, J=22.0 Hz),
112.2, 95.9, 84.1; HR-MS (ESI): m/z= 348.0605, calcd. for
C21H13ClFNO: 349.0670; anal. calcd. for C21H13ClFNO: C
72.11, H 3.75, N 4.00; found: C 71.82, H 3.76, N 3.99.
N-{2-[(4-Fluorophenyl)ethynyl]phenyl}-4-(trifluorometh-
yl)benzamide (3m): The title compound was prepared ac-
cording to the general procedure and purified by column
chromatography to afford a white solid; yield: 78%; mp
4-Fluoro-N-[2-(phenylethynyl)-4-(trifluoromethyl)phen-
yl]benzamide (3h): The title compound was prepared ac-
cording to the general procedure and purified by column
chromatography to afford a yellow solid; yield: 72%.
1H NMR (CDCl3, 400 MHz): d=8.97 (brs, 1H), 8.74 (d, J=
8.8 Hz, 1H), 7.99–7.93 (m, 2H), 7.80 (d, J=2.0 Hz, 1H),
7.64 (dd, J=8.8 Hz, 2.0 Hz, 1H), 7.57–7.53 (m, 2H), 7.48–
7.39 (m, 3H), 7.18 (t, J=8.8 Hz, 2H); 13C NMR (CDCl3,
6
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Iodine-Catalyzed, Stereo- and Regioselective Synthesis of 4-Arylidine-4H-benzo[d]ACTHNUTRGNE[NUG 1,3]oxazines
132–1348C. 1H NMR (CDCl3, 400 MHz): d=8.85 (s, 1H),
8.58 (d, J=8.4 Hz, 1H), 8.11–8.03 (m, 2H), 7.86–7.72 (m,
3H), 7.59–7.38 (m, 4H), 7.19–7.07 (m, 3H); 13C NMR
(CDCl3, 100 MHz): d=163.9 (d, J=58.4 Hz), 163.6, 161.7,
138.9, 138.5, 138.1 (q, J=40.1 Hz), 133.3 (d, J=8.3 Hz),
131.7, 130.2, 130.0, 129.5, 127.6, 127.4, 125.98, 125.95, 125.91,
123.0 (q, J=277.4 Hz), 118.1, 116.1 (d, J=22.8 Hz), 112.4,
96.0, 83.9 (d, J=1.9 Hz); HR-MS (ESI): m/z=382.0859,
calcd. for C22H13ClFNO: 383.0933; anal. calcd. for
C22H13F4NO: C 68.93, H 3.42, N 3.65; found: C 67.18, H
3.39, N 3.72.
pressure. The crude product was chromatographed over
silica gel using ethyl acetate:hexanes as eluent to afford the
title compound.
(Z)-4-Benzylidene-2-phenyl-4H-benzo[d]ACHTNUTRGNE[NUG 1,3]oxazine
(4a): The title compound was prepared according to the gen-
eral procedure and purified by column chromatography to
1
afford a yellow solid; yield: 95%; mp 136–1388C. H NMR
(CDCl3, 400 MHz): d=8.22 (d, J=7.2 Hz, 2H), 7.74 (d, J=
7.2 Hz, 2H), 7.59 (d, J=7.6 Hz, 1H), 7.55–7.22 (m, 9H),
6.22 (s, 1H); 13C NMR (CDCl3, 100 MHz): d=154.9, 145.3,
138.9, 134.7, 131.6, 131.4, 130.4, 128.5, 128.4, 128.3, 127.8,
127.7, 126.7, 126.4, 121.8, 121.6, 101.2; HR-MS (ESI): m/z=
298.1230, calcd. for C21H16NO: 298.1232; anal. calcd. for
C21H15NO: C 84.82, H 5.08, N 4.71; found: C 84.80, H 5.08,
N 4.72.
4-Fluoro-N-[2-(phenylethynyl)phenyl]benzamide
(3n):
The title compound was prepared according to the general
procedure and purified by column chromatography to afford
1
a white solid; yield: 75%; mp 134–1368C. H NMR (CDCl3,
400 MHz): d=8.86 (bs, 1H), 8.58 (d, J=8.4 Hz, 1H), 7.98–
7.93 (m, 2H), 7.55–7.50 (m, 3H), 7.43–7.38 (m, 4H), 7.18–
7.10 (m, 3H); 13C NMR (CDCl3, 100 MHz): d=166.3, 163.8
(d, J=21.2 Hz), 138.8, 131.5, 131.3, 131.1 (d, J=3.0 Hz),
129.9, 129.4 (d, J=9.1 Hz), 129.1, 128.7, 123.6, 122.1, 119.1,
115.9 (d, J=22.0 Hz), 112.2, 97.0, 84.4; HR-MS (ESI): m/z=
316.1132, calcd. for C21H14FNO: 316.1135; anal. calcd. for
C21H14FNO: C 79.98, H 4.47, N 4.44; found: C 79.85, H 4.50,
N 4.40.
N-{2-[(4-Ethylphenyl)ethynyl]phenyl}-4-nitrobenzamide
(3o): The title compound was prepared according to the
general procedure and purified by column chromatography
to afford a yellow solid; yield: 68%; mp 167–1698C.
1H NMR (CDCl3, 400 MHz): d=8.95 (bs, 1H), 8.57 (d, J=
8.0 Hz, 1H), 8.33 (d, J=8.8 Hz, 2H), 8.11 (d, J=8.8 Hz,
2H), 7.56 (d, J=8.0 Hz, 1H), 7.45–7.41 (m, 3H), 7.25 (d, J=
8.0 Hz, 2H), 7.16 (t, J=7.6 Hz, 1H), 2.70 (q, J=7.6 Hz,
2H), 1.27 (t, J=7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz):
d=162.8, 149.8, 145.9, 140.4, 138.2, 131.6, 131.3, 129.8, 128.3,
128.2, 124.3, 124.1, 119.2, 119.0, 112.8, 97.6, 83.4, 28.8, 15.2;
HR-MS (ESI): m/z=371.1395, calcd. for C23H19N2O3:
371.1396; anal. calcd. for C23H19N2O3: C 74.58, H 4.90, N
7.56; found: C 74.58, H 5.01, N 7.46.
(Z)-4-Benzylidene-2-(4-fluorophenyl)-4H-benzo[d]ACHTUNGTRENNUNG[1,3]-
oxazine (4b): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a yellow solid; yield: 71%; mp 120–1228C.
1H NMR (CDCl3, 400 MHz): d=8.15 (d, J=5.6 Hz, 1H),
8.13 (d, J=5.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.49 (d, J=
8.0 Hz, 1H), 7.37 (t, J=8.0 Hz, 2H), 7.30–7.14 (m, 4H), 6.14
(s, 1H); 13C NMR (CDCl3, 100 MHz): d=166.1, 163.6, 153.8,
145.1, 138.7, 134.6, 130.3, 130.0 (d, J=9.1 Hz), 128.4, 128.3,
127.6 (d, J=12.6 Hz), 126.6, 126.4, 121.8, 121.4, 115.4 (d, J=
22.0 Hz), 101.61; HR-MS (ESI): m/z=316.1139, calcd. for
C21H15FNO: 316.1138; anal. calcd. for C21H14FNO: C 79.98,
H 4.47, N 4.44; found: C 78.94, H 4.43, N 4.43.
(Z)-4-Benzylidene-2-(4-chlorophenyl)-4H-benzo[d]ACHTUNGTRENNUNG[1,3]-
oxazine (4c): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a yellow solid; yield: 73%; mp 153–1558C.
1H NMR (CDCl3, 400 MHz): d=8.13 (d, J=8.0 Hz, 2H),
7.69 (d, J=8.0 Hz, 2H), 7.56 (d, J=7.6 Hz, 1H), 7.44–7.22
(m, 8H), 6.21 (s, 1H); 13C NMR (CDCl3, 100 MHz): d=
153.9, 145.1, 138.6, 137.8, 134.6, 130.4, 129.8, 129.1, 128.7,
128.4, 128.3, 127.9, 126.7, 126.5, 121.8, 121.5, 101.7; HR-MS
(ESI): m/z=332.0841, calcd. for C21H15ClNO: 332.0842;
anal. calcd. for C21H14ClNO: C 76.02, H 4.25, N 4.22; found:
C 75.91, H 4.20, N 4.20.
4-Nitro-N-{2-[(trimethylsilyl)ethynyl]phenyl}benzamide
(3p): The title compound was prepared according to the
general procedure and purified by column chromatography
to afford a yellow solid; yield: 85%; mp 132–1348C.
1H NMR (CDCl3, 400 MHz): d=8.94 (bs, 1H), 8.57 (d, J=
8.4 Hz, 1H), 8.35 (d, J=8.8 Hz, 2H), 7.49 (d, J=8.4 Hz,
(Z)-4-Benzylidene-2-(4-nitrophenyl)-4H-benzo[d]ACTHUNTGRNEUNG[1,3]-
oxazine (4d): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a yellow solid; yield: 77%; mp 197–1998C.
1H NMR (CDCl3, 400 MHz): d=8.33 (d, J=8.4 Hz, 2H),
8.28 (d, J=8.4 Hz, 2H), 7.67 (d, J=7.6 Hz, 2H), 7.57 (d, J=
8.0 Hz, 1H), 7.44–7.25 (m, 6H), 6.23 (s, 1H); 13C NMR
(CDCl3, 100 MHz): d=152.8, 149.5, 144.8, 138.2, 137.1,
134.3, 130.6, 128.8, 128.6, 128.5, 128.4, 127.2, 126.8, 123.6,
121.9, 121.7, 102.4; HR-MS (ESI): m/z=343.1083, calcd. for
C21H15N2O3: 343.1081; anal. calcd. for C21H14N2O3: C 73.68,
H 4.12, N 8.18; found: C 73.20, H 4.19, N 7.90.
1H), 7.42 (t, J=7.2 Hz, 1H), 7.11 (t, J=7.2 Hz, 1H), 0.31ACTHNUTRGNEUNG(s,
9H); 13C NMR (CDCl3, 100 MHz): d=162.7, 149.9, 140.2,
138.8, 131.7, 130.2, 128.2, 124.1, 124.0, 118.9, 112.3, 103.1,
100.1;
HR-MS
(ESI):
m/z=361.0983,
calcd.
for
C18H18N2O3SiNa: 361.0986; anal. calcd. for C18H18N2O3Si: C
63.88, H 5.36, N 8.28; found: C 64.13, H 5.56, N 8.26.
General Procedure for the Synthesis of Arylidene-
benzoxazines (4a–4o)
(Z)-4-Benzylidene-2-[4-(trifluoromethyl)phenyl]-4H-
benzo[d]ACTHNUTRGNEUG[N 1,3]oxazine (4e): The title compound was pre-
pared according to the general procedure and purified by
A mixture of the corresponding compound 3 (1.0 mmol),
and iodine (10 mol%) in dry toluene (10.0 mL) was charged
in a flask under an argon atmosphere and stirred for 3 days
at reflux temperature. The reaction was monitered by TLC
analysis. The formed product was extracted with ethyl ace-
tate, followed by washing with water, saturated Na2S2O3 so-
lution and brine. The organic layer was separated, dried
over anhydrous Na2SO4 and concentrated under reduced
column chromatography to afford a yellow solid; yield:
1
54%; mp 88–908C. H NMR (CDCl3, 400 MHz): d=8.32 (d,
J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.70 (d, J=8.4 Hz,
2H), 7.61 (d, J=8.0 Hz, 1H) , 7.42 (t, J=7.2 Hz, 2H), 7.38–
7.28 (m, 4H), 6.26 (s, 1H); 13C NMR (CDCl3, 100 MHz):
d=153.6, 145.0, 138.5, 134.8, 134.5, 133.1 (q, J=33.0 Hz),
130.5, 128.5, 128.4, 128.1, 127.0, 126.7, 125.4 (q, J=3.8 Hz),
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Wen-Chun Lee et al.
FULL PAPERS
124.0 (q, J=271.0 Hz), 121.9, 102.1; HR-MS (ESI): m/z=
366.1104, calcd. for C22H15F3NO: 366.1106; anal. calcd. for
C22H14F3NO: C 72.32, H 3.86, N 3.83; found: C 72.01, H
3.95, N 3.79.
(Z)-4-Benzylidene-2-p-tolyl-4H-benzo[d]ACHTNUTRGNEUNG[1,3]oxazine (4f):
The title compound was prepared according to the general
purified by column chromatography to afford a yellow solid;
yield: 71%. 1H NMR (CDCl3, 400 MHz): d=8.11 (d, J=
8.8 Hz, 2H), 7.78 (s, 1H), 7.67 (dd, J=8.8 Hz and 5.6 Hz,
2H), 7.59–7.52 (m, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.39 (d, J=
8.4 Hz, 1H), 7.12 (t, J=8.8 Hz, 2H), 6.25 (s, 1H); 13C NMR
(CDCl3, 100 MHz): d=162.8, 160.4, 147.0, 143.7, 141.5, 130.2
(d, J=8.3 Hz), 130.1, 129.3, 130.0 (d, J=24.0 Hz), 128.9,
127.2, 127.1, 124.5, 123.9, 123.6 (q, J=274 Hz), 122.1, 119.2,
119.1, 115.5 (d, J=21.2 Hz), 102.6; HR-MS (ESI): m/z=
418.0613, calcd. for C22H12ClF4NO (M+H)+: 418.0616; anal.
calcd. for C22H12ClF4NO: C 63.25, H 2.90, N 3.35; found: C
62.92, H 3.15, N 3.25.
procedure and purified by column chromatography to afford
1
a white solid; yield: 46%; mp 99–1018C. H NMR (CDCl3,
400 MHz): d=8.93 (bs, 1H), 8.62 (d, J=8.4 Hz, 1H), 7.85
(d, J=8.0 Hz, 2H), 7.56–7.38 (m, 7H), 7.27(d, J=8.0 Hz,
2H), 7.10 (td, J=8.0 Hz and 1.2 Hz, 1H), 2.42 (s, 3H);
13C NMR (CDCl3, 100 MHz): d=165.0, 142.6, 139.2, 132.0,
131.4, 131.3, 129.8, 129.5, 128.9, 128.6, 126.9, 123.4, 122.3,
119.1, 112.1, 96.8, 84.5, 21.3; HR-MS (ESI): m/z= 334.1210,
calcd. for C22H17NONa: 334.1208; anal. calcd. for C22H17NO:
C84.86, H 5.50, N 4.50; found: C 84.65, H 5.55, N 4.48.
(Z)-4-Benzylidene-2-phenyl-6-(trifluoromethyl)-4H-
(Z)-4-(4-Fluorobenzylidene)-2-(4-nitrophenyl)-4H-
benzo[d]ACTHNUTRGNEUG[N 1,3]oxazine (4k): The title compound was pre-
pared according to the general procedure and purified by
column chromatography to afford a yellow solid; yield:
76%. 1H NMR (CDCl3, 400 MHz): d=8.33 (s, 4H), 7.67–
7.64 (m, 1H), 7.60 (d, J=7.6 Hz, 2H), 7.42–7.29 (m, 3H),
7.13 (t, J=8.8 Hz, 2H), 6.23 (s, 1H); 13C NMR (CDCl3,
100 MHz): d=162.6, 160.2, 152.7, 149.6, 144.6, 138.2, 137.1,
130.7, 130.5, 130.0 (d, J=7.6 Hz), 128.9, 128.6, 127.3, 123.7,
121.9, 121.6, 115.5 (d, J=21.2 Hz), 101.3; HR-MS (ESI): m/
z=384.1009, calcd. for C22H14F4NO: 384.1011; anal. calcd.
for C21H13FN2O3: C 70.00, H 3.64, N 7.77; found: C 69.63, H
3.65, N 7.74.
benzo[d]ACHTUNGTRENNUNG[1,3]oxazine (4g): The title compound was pre-
pared according to the general procedure and purified by
column chromatography to afford a yellow solid; yield:
1
76%; mp 142–1448C. H NMR (CDCl3, 400 MHz): d=8.22
(d, J=7.2 Hz, 2H), 7.74 (d, J=7.2 Hz, 2H), 7.59 (d, J=
7.6 Hz, 1H), 7.55–7.22 (m, 9H), 6.22 (s, 1H); 13C NMR
(CDCl3, 100 MHz): d=156.5, 144.0, 14.8, 134.0, 132.2, 130.8,
129.5 (q, J=32.6 Hz), 128.7, 128.5, 128.4, 128.1, 127.1, 129.9,
126.8 (q, J=3.8 Hz), 123.9 (q, J=277 Hz), 122.2, 119.1 (q,
J=4.5 Hz), 103.5; HR-MS (ESI): m/z=298.1230, calcd. for
C21H15NO: 298.1232; anal. calcd. for C21H14NO: C 84.82, H
5.08, N 4.71; found: C 84.80, H 5.08, N 4.72.
(Z)-2-(4-Chlorophenyl)-4-(4-Fluorobenzylidene)-4H-
benzo[d]ACTHNUTRGENUG[N 1,3]oxazine (4l): The title compound was prepared
according to the general procedure and purified by column
chromatography to afford a yellow solid; yield: 70%.
1H NMR (CDCl3, 400 MHz): d=8.12 (dt, J=8.4 Hz and
2.4 Hz, 2H), 7.69 (dd, J=8.8 Hz and 5.6 Hz, 2H), 7.58 (d,
J=8.0 Hz, 1H), 7.47 (dt, J=8.4 Hz and 2.4 Hz, 2H), 7.41–
7.24 (m, 4H), 7.11 (t, J=8.8 Hz, 2H); 13C NMR (CDCl3,
100 MHz): dC =162.5, 160.1, 153.9, 145.0, 138.4 (d, J=
62.9 Hz), 130.8, 130.7, 130.6, 130.04, 129.97, 129.0 (J=
22.8 Hz), 128.1, 126.9, 121.9, 121.5, 115.4 (d, J=21.2 Hz),
100.8, 29.7; HR-MS (ESI): m/z=350.0742, calcd. for
C21H14ONClF (M+H)+: 350.0746; anal. calcd. for
C21H13ClFNO: C 72.11, H 3.75, N 4.00; found: C 71.17, H
3.89, N, 3.86.
(Z)-4-Benzylidene-2-(4-fluorophenyl)-6-(trifluoromethyl)-
4H-benzo[d]ACHTUNGTRENNUNG[1,3]oxazine (4h): The title compound was pre-
pared according to the general procedure and purified by
column chromatography to afford a yellow solid; yield:
1
88%; mp 153–1558C. H NMR (CDCl3, 400 MHz): d=8.13
(d, J=5.2 Hz, 1H), 8.11 (d, J=5.2 Hz, 1H), 7.69 (s, 1H),
7.62 (d, J=7.2 Hz, 2H), 7.48 (d, J=8.0 Hz, 1H), 7.39 (t, J=
8.0 Hz, 2H), 7.29–7.23 (m, 2H), 7.09 (t, J=8.0 Hz, 2H), 6.12
(s, 1H); 13C NMR (CDCl3, 100 MHz): d=166.5, 164.0, 162.8,
155.5, 143.8, 141.5, 133.9, 130.4 (d, J=9.1 Hz), 129.1 (q, J=
32.6 Hz), 128.5 (q, J=16.6 Hz), 126.9 (d, J=3.1 Hz), 123.2
(q, J=270.6 Hz), 122.0, 119.0 (q, J=3.8 Hz), 115.7 (d, J=
22.0 Hz), 103.5; HR-MS (ESI): m/z=384.1009, calcd. for
C22H14F4NO: 384.1011; anal. calcd. for C22H13F4NO: C 68.93,
H 3.42, N 3.65; found:C 68.95, H 3.47, N 3.63.
(Z)-4-(4-Fluorobenzylidene)-2-[4-(trifluoromethyl)phen-
yl]-4H-benzo[d]ACTHNUTRGNEUNG[1,3]oxazine (4m): The title compound was
prepared according to the general procedure and purified
by column chromatography to afford a yellow solid; yield:
65%. 1H NMR (CDCl3, 400 MHz): d=8.15–8.08 (m, 2H),
7.69–7.60 (m, 3H), 7.48 (dd, J=8.4 Hz and 1.2 Hz, 1H), 7.30
(t, J=7.6 Hz, 2H), 7.29–7.21 (m, 2H), 7.09 (t, J=8.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz): d=166.5, 164.1, 162.8,
155.5, 143.8, 141.6, 133.9, 130.4 (d, J=9.1 Hz), 129.4 (q, J=
32.6 Hz), 128.9, 128.5 (d, J=16 Hz), 126.7 (q, J=3.1 Hz),
125.0, 122.4, 122.0, 119.1 (q, J=3.8 Hz), 115.7 (d, J=
22.4 Hz), 103.5; HR-MS (ESI): m/z=384.1006, calcd. for
C22H14ONF4 (M+H)+: 384.1004; anal. calcd. for
C22H13F4NO: C 68.93, H 3.42, N 3.65; found: C 68.94, H
3.45, N 3.60.
(Z)-4-Benzylidene-2-(4-chlorophenyl)-6-(trifluoromethyl)-
4H-benzo[d]ACHTUNGTRENNUNG[1,3]oxazine (4i): The title compound was pre-
pared according to the general procedure and purified by
column chromatography to afford a yellow solid; yield:
73%. 1H NMR (CDCl3, 400 MHz): d=8.13 (d, J=8.4 Hz,
2H), 7.78 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.56 (d, J=
8.4 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.0 Hz,
2H), 7.37 (d, J=8.4 Hz, 1H), 7.29 (t, J=7.6 Hz, 1H), 6.27
(s, 1H); 13C NMR (CDCl3, 100 MHz): d=155.7, 143.8, 138.6,
133.9, 129.5, 129.4 (q, J=11.4 Hz), 128.6, 128.5, 127.0 (q, J=
3.8 Hz), 124.6 (q, J=277.6 Hz), 122.27, 119.2 (q, J=3.5 Hz),
103.7.
HR-MS
(ESI):
m/z=400.0719,
calcd.
for
(Z)-4-(4-Fluorobenzylidene)-2-phenyl-4H-benzo[d]ACHTUNGTRENNUNG[1,3]-
C22H14ClF3NO (M+H)+: 400.0716; anal. calcd. for
C22H13ClF3NO: C 66.09, H 3.28, N 3.50; found: C 65.48, H
3.33, N 3.49.
oxazine (4n): The title compound was prepared according to
the general procedure and purified by column chromatogra-
phy to afford a yellow solid; yield: 92%; mp 163–1658C.
1H NMR (CDCl3, 400 MHz): d=8.16 (d, J=7.2 Hz, 2H),
7.66 (dd, J=8.4 Hz and J=5.4 Hz 2H), 7.52–7.45 (m, 4H),
7.36–7.28 (m, 2H), 7.26–7.18 (m, 1H), 7.08 (t, 2H, J=
(Z)-2-(4-Chlorophenyl)-4-(4-fluorobenzylidene)-6-(tri-
fluoromethyl)-4H-benzo[d]
pound was prepared according to the general procedure and
ACHTUNGTRNE[NUNG 1,3]oxazine (4j): The title com-
8
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Iodine-Catalyzed, Stereo- and Regioselective Synthesis of 4-Arylidine-4H-benzo[d]ACTHNUTRGNE[NUG 1,3]oxazines
8.4 Hz); 13C NMR (CDCl3, 100 MHz): d=162.4, 159.9,
154.8, 145.0, 138.8, 131.7, 131.4, 130.4, 129.9 (d, J=7.6 Hz),
128.5, 127.8 (d, J=5.3 Hz), 126.8, 121.8, 121.5, 115.3 (d, J=
21.2 Hz), 100.5; HR-MS (ESI): m/z=316.1144, calcd. for
C21H14FNO: 316.1142; anal. calcd. for C21H14FNO: C 79.98,
H 4.47, N, 4.44; found: C 79.71, H 4.74, N 4.39.
(Z)-4-(4-Ethylbenzylidene)-2-(4-nitrophenyl)-4H-
benzo[d]ACHTUNGTRENNUNG[1,3]oxazine (4o): The title compound was pre-
pared according to the general procedure and purified by
d=140.5, 136.9, 135.5, 131.8, 131.0, 130.9, 129.6, 129.3, 129.2,
128.9, 128.8, 128.6, 128.1, 127.0, 125.3, 123.5, 123.2, 31.9;
HR-MS (ESI): m/z=331.1246, calcd. for C21H16N2O (M+
H)+: 331.1247.
4-Benzyl-2-(4-nitrophenyl)quinazoline 3-oxide (8d): The
title compound was prepared and purified by column chro-
matography to afford a yellow solid; yield:85%; mp 170–
1
1728C. H NMR (CDCl3, 400 MHz): d=8.55 (td, J=8.8 Hz,
2.0 Hz, 2H), 8.32 (td, J=8.8 Hz, 2.4 Hz), 8.6 (t, J=8.4 Hz),
7.81–7.71 (m, 2H), 7.41 (d, J=8.0 Hz, 2H), 7.31–7.20 (m,
3H), 4.81 (s, 2H); 13C NMR (CDCl3, 100 MHz): d=153.7,
152.7, 148.7, 140.4, 138.6, 135.2, 131.6, 131.3, 130.4, 129.5,
128.9, 128.8, 127.1, 123.9, 123.3, 122.9, 31.9; HR-MS (ESI):
m/z=358.1191, calcd. for C21H16N3O3: 358.1192; anal. calcd.
for C21H16N3O3: C 70.58, H 4.232, N 11.76; found: C 70.42,
H 4.31, N 11.76.
4-Benzyl-2-[4-(trifluoromethyl)phenyl]quinazoline 3-oxide
(8e): The title compound was prepared and purified by
column chromatography to afford a solid; yield: 80%; mp
136–1388C. 1H NMR (CDCl3, 400 MHz): d=8.44 (d, J=
8.8 Hz, 2H), 8.04 (t, J=8.8 Hz, 2H), 7.77–7.67 (m, 4H), 7.41
(d, J=7.6 Hz, 2H), 7.31–7.18 (m, 3H), 4.81 (s, 2H);
13C NMR (CDCl3, 100 MHz): d=153.7, 153.4, 140.5, 136.0,
135.4, 132.3 (q, J=8.1 Hz), 131.1, 130.8, 130.0, 129.4, 128.9,
128.8, 127.1, 124.8 (q, J=15.2 Hz), 123.8, 123.3 (q, J=
271.3 Hz), 31.9; HR-MS (ESI): m/z=381.1210, calcd. for
C22H16F3N2O (M+H)+: 381.1209; anal. calcd. for
C22H15F3N2O: C 69.47, H 3.97, N 7.36; found: C 69.48, H
4.02, N 7.36.
4-Benzyl-2-p-tolylquinazoline 3-oxide (8f): The title com-
pound was prepared and purified by column chromatogra-
phy to afford a pale yellow solid; yield: 66%. 1H NMR
(CDCl3, 400 MHz): d=88.23 (dt, J=2.0 Hz and 8.4 Hz, 2H),
8.01–7.91 (m, 2H), 7.69–7.57 (m, 2H), 7.39 (d, J=7.6 Hz,
2H), 7.32–7.161 (m, 5H), 4.78 (s, 2H); 13C NMR (CDCl3,
100 MHz): d=155.0, 152.9, 141.0, 140.4, 135.7, 130.6, 130.3,
129.7, 129.1, 128.9, 128.7, 128.6, 128.5, 126.8, 123.3, 123.1,
31.8, 21.5; HR-MS (ESI): m/z=327.1492, calcd. for
C22H19N2O (M+H)+: 327.1491; anal. calcd. for C22H19N2O:
C 80.96, H 5.56, N 8.58; found: C 79.03, H 5.52, N 8.36.
4-Benzyl-2-phenyl-6-(trifluoromethyl)quinazoline 3-oxide
(8g): The title compound was prepared and purified by
column chromatography to afford a solid; yield: 55%.
1H NMR (CDCl3, 400 MHz): d=8.33–8.27 (m, 3H), 8.15 (d,
J=4.4 Hz, 1H), 7.88 (dd, J=4.4 Hz, 1.0 Hz, 1H), 7.55–7.49
(m, 3H), 7.4 (d, J=3.8 Hz, 2H), 7.31–7.21 (m, 4H), 4.81 (s,
2H); 13C NMR (CDCl3, 100 MHz): d=153.5, 153.1, 131.9,
131.4, 130.5, 130.4, 128.9, 128.8, 128.0, 127.2, 126.3 (q, J=
6.0 Hz), 123.8 (q, J=272.4 Hz), 122.9, 120.9 (q, J=1.9 Hz),
32.0; HR-MS (ESI): m/z=313.12096, calcd. for C22H16F3N2O
(M+H)+: 381.12092; anal. calcd. for C22H16F3N2O: C 69.47,
H 3.97, N 7.36; found: C 69.04, H 4.06, N 7.36.
column chromatography to afford a yellow solid; yield:
1
65%; mp 163–1658C. H NMR (CDCl3, 400 MHz): d=8.40
(d, J=9.2 Hz, 2H), 8.34 (d, J=9.2 Hz, 2H), 7.62 (t, J=
8.0 Hz, 3H), 7.40–7.27 (m, 5H), 6.26 (s, 1H), 2.71 (q, J=
8.4 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H); 13C NMR (CDCl3,
100 MHz): dC =153.0, 149.5, 144.3, 143.1, 138.2, 137.3, 131.7,
130.4, 128.8, 128.7, 128.4, 128.0, 127.1, 123.6, 122.0, 121.9,
102.5, 28.6, 15.4; HR-MS (ESI): m/z=371.1393, calcd. for
C23H19N2O3: 371.1396; anal. calcd. for C23H18N2O3: C 74.58,
H 4.90, N 7.56; found: C 74.14, H 4.69, N, 7.29.
General Procedure and Characterization Data for
Quinazoline 3-Oxides (8a–8o)
To a solution of benzoxazine 4 (1.0 mmol) in a mixture of
dichloromethane and methanol (4:1, 10 mL) was added
K2CO3 (10 mol%) and hydroxylamine hydrochloride
(10 equiv) and the mixture stirred at room temperature for
10 h. The reaction was monitored by TLC analysis. The sol-
vents were removed under reduced pressure and the the
crude product was extracted with ethyl acetate followed by
washing with water and brine and drying over anhydrous
Na2SO4. The crude product obtained was purifed by column
chromatography using a mixture of ethyl acetate and hex-
anes to afford the title compound.
4-Benzyl-2-phenylquinazoline 3-oxide (8a): The title com-
pound was prepared and purified by column chromatogra-
phy to afford a pale yellow solid; yield: 75%. 1H NMR
(CDCl3, 400 MHz): d=8.32–8.21 (m, 2H), 8.00–7.94 (m,
2H), 7.69–7.58 (m, 2H), 7.51–7.46 (m, 4H), 7.40 (d, J=
7.2 Hz, 2H), 7.28–7.16 (m, 2H). 4.78 (s, 2H); 13C NMR
(CDCl3, 100 MHz): dC =154.9, 152.9, 140.4, 135.6, 132.5,
130.7, 130.6, 130.2, 129.3, 129.2, 128.9, 128.7, 127.9, 127.8,
126.8, 123.4, 123.1; HR-MS (ESI): m/z=313.1330, calcd. for
C21H17N2O (M+H)+: 313.1335; anal. calcd. for C21H17N2O:
C 80.75, H 5.16, N 8.97; found: C 79.84, H 5.18, N, 8.76.
4-Benzyl-2-(4-fluorophenyl)quinazoline 3-oxide (8b): The
title compound was prepared and purified by column chro-
1
matography to afford a solid; yield: 51%. H NMR (CDCl3,
400 MHz): dH =8.42–8.40 (m, 2H), 8.04–7.90 (m, 2H), 7.76–
7.60 (m, 2H), 7.40 (d, J=8.4 Hz, 2H), 7.30–7.13 (m, 5H),
4.81 (s, 2H); 13C NMR (CDCl3, 100 MHz): dC =165.5, 163.0,
153.9, 153.2, 140.5, 135.6, 132.9 (d, J=8.3 Hz), 130.9, 129.5,
129.2, 128.8 (d, J=14.4 Hz), 127.0, 123.5, 123.2, 115.1, 114.8,
31.9; HR-MS (ESI): m/z=331.1246, calcd. for C21H16FN2O
(M+H)+: 331.1247; anal. calcd. for C21H15FN2O: C 76.35, H
4.58, N 8.48; found:C 76.16, H 4.69, N 8.52.
4-Benzyl-2-(4-fluorophenyl)-6-(trifluoromethyl)quinazo-
line 3-oxide (8h): The title compound was prepared and pu-
rified by column chromatography to afford a yellow solid;
1
yield: 81%. H NMR (CDCl3, 200 MHz): d=8.47–8.42 (m,
2H), 8.26 (t, J=0.8 Hz, 1H), 8.13 (d, J=8.0 Hz, 1H), 7.88
(dd, J=2.0 Hz, 8.8 Hz, 1H), 7.40–7.37 (m, 2H), 7.31–7.15
(m, 5H), 4.79 (s, 2H); 13C NMR (CDCl3, 100 MHz): d=
165.8, 163.3, 155.6, 153.7, 141.1, 134.9, 133.1 (d, J=8.3 Hz),
130.2 (q, J=32.6 Hz), 130.4, 128.9 (d, J=9.8 Hz), 127.9 (d,
J=3.8 Hz), 127.3, 126.4 (q, J=3.0 Hz), 123.1 (q, J=271.3),
4-Benzyl-2-(4-chlorophenyl)quinazoline 3-oxide (8c): The
title compound was prepared and purified by column chro-
matography to afford a pale yellow solid; yield: 68%.
1H NMR (CDCl3, 400 MHz): d=8.34–8.31 (m, 2H), 8.04–
7.99 (m, 2H), 7.77–7.65 (m, 2H), 7.41–7.32 (m, 2H), 7.31–
7.19 (m, 5H), 4.80 (s, 2H); 13C NMR (CDCl3, 100 MHz):
Adv. Synth. Catal. 0000, 000, 0 – 0
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Wen-Chun Lee et al.
FULL PAPERS
122.9, 120.9 (q, J=4.6 Hz), 115.1 (d. J=22.0 Hz), 32.0; HR-
MS (ESI): m/z=399.1109, calcd. for C22H15F4N2O (M+H)+:
399.1115; anal. calcd. for C22H15F4N2O: C 66.33, H 3.54, N
7.03; found: C 66.04, H 3.58, N 6.95.
4-(4-Fluorobenzyl)-2-phenylquinazoline 3-oxide (8n): The
title compound was prepared and purified by column chro-
1
matography to afford a yellow solid; yield: 54%. H NMR
(CDCl3, 400 MHz): d=8.29 (m, 2H), 8.08–8.04 (m, 1H),
7.99–7.97 (m, 1H), 7.76–7.65 (m, 2H), 7.55–7.47 (m, 3H),
7.43–7.37 (m, 2H), 6.98–6.94 (m, 2H), 4.76 (s, 2H);
13C NMR (CDCl3, 100 MHz): d=163.0, 160.6, 155.1, 152.8,
140.5, 132.5, 131.2 (d, J=3.1 Hz), 130.85 (d, J=7.6 Hz),
130.6 , 130.5, 130.2, 129.6, 129.4, 127.9, 123.4, 122.9, 115.6 (d,
J=21.2 Hz), 31.2; anal. calcd. for C21H15FN2O: C 76.35, H
4.58, N 8.48; found: C 75.04, H 5.43, N, 7.44.
4-Benzyl-2-(4-chlorophenyl)-6-(trifluoromethyl)quinazo-
line 3-oxide (8i): The title compound was prepared and puri-
fied by column chromatography to afford a pale yellow
1
solid; yield: 36%. H NMR (CDCl3, 400 MHz): d=8.36 (dt,
J=2.4 Hz, 9.2 Hz, 2H), 8.27 (t, J=0.8 Hz, 1H), 8.14 (d, J=
8.8 Hz, 1H), 7.90 (dd, J=1.6 Hz, 8.8 Hz, 1H), 7.48 (dt, J=
2.4 Hz, 9.2 Hz, 2H), 7.38 (dt, J=1.6 Hz, 8.4 Hz, 2H), 7.32–
7.21 (m, 3H), 4.80 (s, 2H); 13C NMR (CDCl3, 100 MHz):
d=155.7, 153.8, 141.1, 133.6 (q, J=253.7 Hz), 130.5, 130.3,
129.0, 128.9, 128.3, 127.3, 126.5 (q, J=3.0 Hz), 122.9, 120.9
(q, J=4.5 Hz), 120.4; anal. calcd. for C22H14ClF3N2O: C
63.70, H 3.40, N 6.75; found: C 63.74, H 3.65, N 6.49.
4-(4-Ethylbenzyl)-2-(4-nitrophenyl)quinazoline
3-oxide
(8o): The title compound was prepared and purified by
column chromatography to afford a yellow solid; yield:
1
60%. H NMR (CDCl3, 400 MHz): d=88.55 (d, J=9.2 Hz,
2H), 8.32 (d, J=9.2 Hz, 2H), 8.06 (d, J=9.2 Hz, 2H), 7.81–
7.71 (m, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.4 Hz,
2H), 4.78 (s, 2H), 2.58 (q, J=11.2 Hz, 2H), 1.17 (t, J=
7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d=153.9, 152.7,
148.7, 143.1, 140.4, 138.6, 132.4, 131.6, 131.3, 130.3, 129.5,
128.9, 128.3, 123.9, 123.4, 122.9, 31.5, 28.4, 15.4; HR-MS
(ESI): m/z=386.1499, calcd. for C23H19N3O3 (M+H)+:
386.1495; anal. calcd. for C23H19N3O3: C 71.67, H 4.97, N
10.90; found: C 71.43, H 5.00, N 10.82.
2-(4-Chlorophenyl)-4-(4-fluorobenzyl)-6-(trifluorome-
thyl)quinazoline 3-oxide (8j): The title compound was pre-
pared and purified by column chromatography to afford
1
a solid; yield: 31%. H NMR (CDCl3, 400 MHz): d=8.37–
8.34 (m, 2H), 8.25 (s, 1H), 8.15 (d, J=8.8 Hz, 1H), 7.91 (dd,
J=1.6 Hz, J=8.8 Hz, 1H), 7.50–7.47 (m, 2H), 7.39–7.34 (m,
2H), 7.01–6.95 (m, 2H), 4.74 (s, 2H); 13C NMR (CDCl3,
100 MHz): dC =163.1, 160.7, 155.6, 153.5, 141.1, 137.7, 132.0,
131.6, 131.3, 130.5(t, J=7.5 Hz), 130.1, 128.2, 126.6 (d, J=
12 Hz), 122.8, 120.6 (q, J=4.5 Hz), 115.9, 115.7,31.2.
Supporting Information
4-(4-Fluorobenzyl)-2-(4-nitrophenyl)quinazoline 3-oxide
(8k): The title compound was prepared and purified by
column chromatography to afford a solid; yield: 55%; mp
208–2098C. 1H NMR (CDCl3, 400 MHz): d=8.50 (td, J=
8.8 Hz, 2.4 Hz, 2H), 8.34 (td, J=8.8 Hz, 2.0 Hz, 2H), 8.10–
8.01 (m, 2H), 7.83–7.74 (m, 2H), 7.40–7.36 (m, 2H), 6.97 (t,
J=8.4 Hz, 2H), 4.77 (s, 2H); 13C NMR (CDCl3, 100 MHz):
dC =163.1, 160.7, 153.1 (d, J=69.7 Hz), 148.8, 140.5, 138.5,
131.48 (d, J=15.9 Hz), 130.8, 130.6, 130.5, 130.4, 129.7,
123.7, 123.1, 122.9, 115.7 (d, J=21.2 Hz), 31.1; HR-MS
(ESI): m/z=376.1092, calcd. for C21H14FN3O3 (M+H)+:
376.1088; anal. calcd. for C21H14FN3O3: C 67.2, H 3.76, N
11.19; found: C 66.85, H 3.76, N 11.09.
1H and 13C NMR spectra of all compounds are available as
Supporting Information.
Acknowledgements
We thank the National Science Council of the Republic of
China for financial support. This work was also supported by
a grant from the Kaohsiung Medical University Research
Foundation.
2-(4-Chlorophenyl)-4-(4-fluorobenzyl)quinazoline 3-oxide
(8l): The title compound was prepared and purified by
column chromatography to afford a white solid; yield: 81%.
1H NMR (CDCl3, 400 MHz): dH =8.34–8.30 (m, 2H), 8.05–
7.97 (m, 2H), 7.77–7.67 (m, 2H), 7.48–7.45 (m, 2H), 7.39–
7.35 (m, 2H), 6.98–6.92 (m, 2H), 4.74 (s, 2H); 13C NMR
(CDCl3, 100 MHz): d=163.0, 160.5, 153.8, 153.0, 140.4,
137.0, 131.8, 131.1, 131.0, 130.8, 130.6, 130.5, 129.7, 129.3,
128.1, 123.3, 122.9, 115.7, 115.5, 31.1; anal. calcd. for
C21H14ClFN2O: C 69.14, H 3.87, N 7.68; found: C 67.53, H
3.95, N 7.36.
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4-(4-Fluorobenzyl)-2-[4-(trifluoromethyl)phenyl]quinazo-
line 3-oxide (8m): The title compound was prepared and pu-
rified by column chromatography to affgord an off-white
1
solid; yield: 91%. H NMR (CDCl3, 400 MHz): d=8.42 (d,
J=8.0 Hz, 2H), 8.05 (ddd, J=0.8 Hz, 8.4 Hz and 16.8 Hz,
2H), 7.81–7.71 (m, 4H), 7.41–7.38 (m, 2H), 6.96 (t, J=
8.8 Hz, 2H), 4.77 (s, 2H); 13C NMR (CDCl3, 100 MHz): d=
163.1, 160.6, 153.4 (d, J=44.8 Hz), 140.5, 135.9, 132.4 (q, J=
28.6 Hz), 131.2, 130.9 (d, J=3.0 Hz), 130.8, 130.7, 130.6,
130.1, 129.6, 124.8 (q, J=3.8 Hz), 123.9 (q, J=21.3 Hz),
123.6, 123.1, 115.6, 31.2; anal. calcd. for C22H14F4N2O: C
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ÞÞ
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FULL PAPERS
12 Iodine-Catalyzed, Stereo- and Regioselective Synthesis of 4-
Arylidine-4H-benzo[d]ACTHNUGRTENUNG[1,3]oxazines and their Applications
for the Synthesis of Quinazoline 3-Oxides
Adv. Synth. Catal. 2012, 354, 1 – 12
Wen-Chun Lee, Ho-Chuan Shen, Wan-Ping Hu,
Wei-Sheng Lo, Chebrolu Murali, Jaya Kishore Vandavasi,
Jeh-Jeng Wang*
12
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These are not the final page numbers!