Palladium-Catalyzed Olefination of 4H-Benzo[d][1,3]oxazin-4-one Derivatives with Activated Alkenes via Preferential Cyclic Imine-N-Directed Aryl C-H Activation

Article abstract of DOI:10.1002/ejoc.201900935

A palladium-catalyzed chelation-assisted selective ortho C-H bond olefination of biologically active 4H-benzo[d][1,3] oxazin-4-one derivatives with activated olefins has been achieved. The products are obtained in good yields with high regio- and stereose

Full text of DOI:10.1002/ejoc.201900935

A Journal of
Accepted Article
Title: Palladium-catalyzed olefination of 4H-Benzo[d][1, 3] oxazin-4-one
derivatives with activated alkenes via preferential cyclic imine-N-
directed aryl C-H activation
Authors: Subir Panja, Srabani Maity, Biju Majhi, and Brindaban
Chandra Ranu
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900935
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
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Palladium-catalyzed olefination of 4H-Benzo[d][1, 3] oxazin-4-one
derivatives with activated alkenes via preferential cyclic imine-N-
directed aryl C-H activation
Subir Panja,[a] Srabani Maity,[a] Biju Majhi,[a] and Brindaban C. Ranu*[a]
Abstract: A palladium-catalyzed chelation-assisted selective ortho
Figure 1.
benzo[d][1,3]oxazin-4-one moiety.
A
few biologically active molecules containing 4H-
C-H bond olefination of biologically active 4H-benzo[d][1, 3]
oxazin-4-one derivatives with activated olefins has been achieved.
The products are obtained in good yields with high regio- and
stereoselectivities. This new protocol has been demonstrated to
provide
a
variety of olefinated-4H-benzo[d][1,3]oxazin-4-one
Moreover, these moieties also serve as versatile building
blocks in organic synthesis. For example, they are used as
synthetic intermediates for the synthesis of biologically active
derivatives. The site selectivity of the reaction was explained by
DFT study.
benzoxazinethiones,
benzothiazinethiones,
substituted
amidobenzoates, 4-hydroxyquinolinones and quinazolinones
(Figure 2).[2] Thus, the development of efficient procedure for
the functionalization of benzoxazinone has received
considerable attention.
Introduction
Benzoxazinone unit is of much importance as it is present in a
large number of natural products, drugs and pharmaceuticals
having diverse activities. They are reported to exhibit activities
such as antifungal, antibacterial, herbicidal, chymotrypsin
inhibitor, HSV-1 protease inhibitor, serine proteases inhibitor,
inhibitor of leucocyte elastase among others (Figure 1).[1]
Figure 2. Application of benzoxazinone in the synthesis of bioactive
quinazolin-4(3H)-ones.
The unactivated C-H bonds are abundant in organic
molecules. So functionalization of unactivated C-H bonds is of
much potential. One of the major advantages of this technique
is
elimination of prefunctionalization step and thus this
strategy leads to step and atom economy and minimization of
waste. During last few years tremendous development has
been noticed towards the use of C-H activation tool for
efficient construction of functional molecules.[3] However,
[a] Mr. Subir Panja, Ms. Srabani Maity, Dr. Biju Majhi, Prof. Dr. Brindaban C.
Ranu
School of Chemical Sciences, Indian Association for the Cultivation of
Science, Jadavpur, Kolkata – 700032, India.
E-mail: ocbcr@iacs.res.in. Homepage: http://iacs.res.in/faculty-
profile.html?id=57
functionalization at
a selective C-H bond in molecules
possessing more than one similar type of C-H bond is a difficult
task[4] although some progress has been made in recent
times.[5]
The C-H bond olefination is an important reaction as an
alkene moiety can be a source of manipulation leading to
various active molecules. The palladium-catalyzed coupling
between aryl halide and alkenes (Mizoroki-Heck reaction) is
widely used for olefination.[6] However, there are limitations of
Electronic supplementary information (ESI) available: Additional
experimental information, copies of 1H, 13CNMR spectra of all compounds
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
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this reaction with respect to yields and cost of aryl halides.[7]
Another approach involves direct olefination of C-H bonds via
Fujiwara-Moritani reaction.[8] This reaction requires excess
use of arene and the regioselectivity is not always
satisfactory. These factors limit their application. During last
few years a few elegant methods involving directing group
assisted C(aryl)−H olefination were reported.[9] These
include olefinations using amides,[9a] carbamates[9b] and
urea[9c] as directing groups among others. Considering the
importance of benzoxazinone and its derivatives we
report here olefination of this unit with activated alkenes via
preferential cyclic imine-N-directed aryl C-H activation
(Scheme 1). The olefination of benzoxazinone was not
addressed earlier.
Entry
Catalyst
Oxidant
Additive
Solvent
Temp.
(oC)
Time
Yields
(%)
1
2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(PPh3)4
Pd(OAc)2
-
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
(NH4)2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
-
PhCl
THF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
110
110
110
110
110
110
110
110
110
85
12
12
12
12
12
12
12
12
12
12
12
18
24
24
41
18
54
31
59
-
-
3
-
-
4
5
-
6
-
7
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
-
56
33
65
68
47
65
75
79
8
AdCO2H
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
9
10
11
12
13
14[c]
Scheme 1. Olefination of benzoxazinone unit with activated alkenes.
50
85
Results and Discussion
85
85
Initially, as a test run 2-phenyl-4H-benzo[d][1,3]oxazin-4-
one was reacted with butyl acrylate in the presence of
Pd(acac)2 (15 mol %), K2S2O8 (2 equivalents) as an oxidant in
[a]Reaction conditions: 2-phenyl-4-H-benzo[d][1,3]oxazin-4-one (0.1 mmol),
butyl acrylate (0.5 mmol), Pd(acac)2 (10 mol %), K2S2O8 (1.5 equiv.), PhCl
solvent (3 ml), 110 oC, Ar atmosphere, 12 h. [b]Isolated yield. [c]O2 atm.
o
chlorobenzene at 110 C under argon atmosphere for12 h. A
product was isolated in 41 % yield (entry 1, Table 1) whose
spectroscopic data (1H and 13C NMR) are in good agreement
with the expected olefinated compound. To standardize the
reaction conditions a series of experiments were performed
with variation of reaction parameters such as catalyst, oxidant,
additives, solvent, temperature and time (for details see
supporting information). The change of solvent from
chlorobenzene to dichloroethane improved the yield to some
extent (entry 3, Table 1). Screening of different Pd catalysts
indicated Pd(OAc)2 a better choice (entry 5, Table 1). In the
absence of Pd catalyst the reaction did not proceed (entry 6,
Table 1). Similarly we tested various oxidizing agents.
However, no one is better than K2S2O8. It was found that the
reaction provided an improved result with addition of pivalic
Thus
in
a
general
procedure,
2-phenyl-4H-
benzo[d][1,3]oxazin-4-one was reacted with butyl acrylate in
the presence of K2S2O8, and 1.5 equivalent of pivalic acid in
dichloroethane at 85 C for 24 h under O2. After the reaction
was over the product was isolated by standard work-up
followed by column chromatography.
o
After having the optimized condition in
hand we
investigated the scope of the reaction. A wide range of 2-aryl-
4H-benzo[d][1,3]oxazin-4-ones were subjected to reaction with
butyl acrylate by this procedure to produce the corresponding
olefinated products in good to excellent yields (Table 2).
Electron
donating
functional
groups
o
such as -Me, -Et, -nBu, -tBu, -OMe, -Ph bearing substrates
provided the corresponding products (3b, 3c, 3d, 3e, 3f, 3g) in
excellent yields. Halogen-containing 2-aryl-4H-benzo[d][1,
3]oxazin-4-ones were also compatible with this reaction (3h,
3i). The halogen functionalities provide scope for further
acid (entry 9, Table 1). The best result was obtained at 85 C
(entry 10, Table 1). Screening of reaction time suggests 24 h
as the optimum for a good yield (entry 13, Table 1). It was also
observed that higher yield was obtained under O2 atmosphere
compared to argon (entry 14, Table 1). As acrylates are prone
to polymerization at higher temperature 5 equiv. of butyl
acrylate and 3 equiv. of methyl acrylate (see SI) were used.
Thus, with the optimized conditions the product was obtained
in 79% yield (entry 14, Table 1).
manipulation.
The
ortho-substituted
2-aryl-
4Hbenzo[d][1,3]oxazin-4-one was found to produce lower
yields (3k, 3l). This procedure is acceptable to substrates
containing -CF3 functional group (3j, 3l) and usually these
molecules show promising biological activities. A library of
olefinated benzoxazines with substitutions at both the aromatic
rings were synthesized in good yields using this protocol. The
reaction of 2- aryl-4H-benzo[d][1,3]oxazin-4-one substituted
at 8 position provided the product in lower yield (3t and 3u). It
is possibly because of the steric factors.
Table 1. Optimization of the reaction conditions.[a,b]
Table 2. Pd-catalyzed C-H olefination of benzoxazinone derivatives with
butyl acrylate.[a,b]
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
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reaction (Table 4). The reactions of furanyl and thiophenyl ring
attached benzoxazine-4-ones proceeded well although the
yields are relatively low compared to other reactions. These
molecules might be of potential in pharmaceutical industry.
This type of C-H olefination of benzoxazinones containing
heteroarene unit was not reported.
a
Table 4. Pd-catalyzed C-H olefination of heteroaryl benzoxazinone with butyl
and methyl acrylate.[a,b]
[a]Reaction conditions: benzoxazinone derivatives (0.5 mmol), butyl acrylate
(2.5 mmol), Pd(OAc)2 (10 mol %), K2S2O8 (0.75 mmol), PivOH (1 mmol),
dichloroethane (3 ml), 85 oC, O2 atmosphere, 24 h. [b]Isolated yield.
To test the generality of this procedure it was further
extended to the reaction with methyl acrylate (Table 3). The 2-
aryl-4H-benzo[d][1,3]oxazin-4-ones underwent reaction with
methyl acrylate without any difficulty.
benzoxazinones containing substituents on both the aromatic
rings participated in the reaction providing good yields.
A
variety of
[a]Reaction conditions: 2-heteroaryl-4H-benzo[d][1,3]oxazin-4-one (0.5
mmol), butyl acrylate (2.5 mmol), methyl acrylate (1.5 mmol), Pd(OAc)2 (10
mol %), K2S2O8 (0.75 mmol), PivOH (1 mmol), dichloroethane (3 ml), 85 oC,
O2 atmosphere, 24 h. [b]Isolated yield.
Table 3. Pd-catalyzed C-H olefination of benzoxazinone derivatives with
methyl acrylate.[a,b]
To check the regioselectivity of the reaction a few meta-
substituted benzoxazinones were investigated (Table 5). There
Table 5. Pd-catalyzed C-H olefination of meta-substituted 2-aryl-4H-benzo
[d][1,3] oxazin-4-one with butyl and methyl acrylate.[a,b]
[a]Reaction conditions: benzoxazinone derivatives (0.5 mmol), methyl
acrylate (1.5 mmol), Pd(OAc)2 (10 mol %), K2S2O8 (0.75 mmol), PivOH (1
mmol), dichloroethane (3 ml), 85 oC, O2 atmosphere, 24 h. [b]Isolated
yield.
Further to check the diversity of this protocol the
heteroarene-substituted benzoxazinones were subjected to
[a]Reaction conditions: meta-substituted 2-aryl-4H-benzo[d][1,3]oxazin-4-one
(0.5 mmol), butyl acrylate (2.5 mmol), methyl acrylate (1.5 mmol), Pd(OAc)2
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(10 mol %), K2S2O8 (0.75 mmol), PivOH (1 mmol), dichloroethane (3 ml), 85
oC, O2 atmosphere, 24 h. [b]Isolated yield.
elimination, and reductive elimination of HOAc to provide the
olefinated product and Pd(0) is reoxidized into Pd(II) by oxidant
to restart the next cycle. It is likely that PivOH binds with the
metal of metalocycle to lower the activation energy.
is a possibility of functionalization at two adjacent carbon
centers. However, it was found that reaction goes through less
hindered site giving only one product. The structure of one of
the products, 6e was confirmed by X-ray diffraction analysis
(See SI).[10]
To check the generality of this reaction we investigated this
olefination with other olefins such as acrylamide,
acetophenone and styrene; however the reactions are not
successful either giving very low or no yield of product.
To check the synthetic utility a gram scale reaction was
performed (Scheme 2). The yield was comparable.
Scheme 2. A gram scale synthesis by our procedure.
In principle, there are possibilities of three chelating
cycles directed by three different centers -N, -O, -CO (Figure 3).
The energy of each possible metallocycle was calculated in its
optimized structure by DFT method. From DFT calculation it
was found that N- directed metallocycle (A) is more stable by
12.5 kcal/mole than O- directed metallocycle (B) and 31.4
kcal/mole
Scheme 3. Possible reaction pathway.
Conclusions
In conclusion, we have developed an efficient protocol for
the olefination of 2-aryl-4H-benzo[d][1,3]oxazin-4-ones with
activated olefins via C-H activation catalyzed by palladium. A
library of olefinated-2-aryl- 4H-benzo[d][1,3]oxazin-4-ones
were achieved using butyl and methyl acrylates by this simple
procedure. The reaction is highly regioselective and applicable
to heteroarene-benzoxazinones too. These molecules may
have much potential in organic synthesis and in
pharmaceutical industry. To the best of our knowledge this is
the first report on the olefination of 2-aryl-4H-benzo[d]
[1,3]oxazin-4-ones via C-H activation.
(A)
(B)
(C)
Experimental Section
Figure 3. DFT calculation of the possible metallocycles.
General Methods
more stable than C=O directed metallocycle(C). So it may be
concluded that the reaction goes through preferential N-
directed chelation (see SI).
IR spectra were taken as thin films for liquid compounds and as KBr
pellets for solids. NMR spectra were recorded at 300, 400, 500 MHz for
1H spectra and at 75, 100, 125 MHz for 13C spectra in CDCl3 solutions.
HRMS analysis was performed in a Qtof mass analyzer using ESI
ionization method. Anthranilic acids, benzoyl chloride derivatives, n-
butyl acrylate, methyl acrylate, Pd(OAc)2, PivOH and K2S2O8 were
purchased from Sigma-Aldrich.
Based on the previous reports[11] a possible reaction
mechanism is proposed as outlined in Scheme 3. Initially in the
presence of Pd(OAc)2 benzoxazinone forms a 5-membered
palladacycle (II) intermediate A which interacts with alkyl
acrylate and forms the intermediate B. In the next step, the
intermediate B undergoes olefin insertion, beta-hydrogen
Representative experimental procedure for the preparation of 2-
aryl-4H benzo[d][1,3] oxazin-4-ones following a reported one[12]
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To a solution of anthranilic acid (10 mmol, 1.37 g) in pyridine (30 mL)
cooled at 0 oC in an ice bath was added an acid chloride (20 mmol)
dropwise slowly and carefully with proper control. An exothermic
reaction occurred. The reaction mixture was stirred for 5 min at 0 oC.
The ice bath was removed and the reaction mixture was allowed to
warm slowly to room temperature (30 oC). The reaction mixture was
further stirred for 0.5 h at room temperature. After completion of the
reaction (TLC) the mixture was poured into ice-cold water (200 mL) and
the residue was collected by filtration and washed with cold water
(3×60 mL) and dried. The crude benzoxazin-4-one was recrystallized
from ethanol as white prismatic needles.
(4-Butylphenyl)-4H-benzo[d][1,3]oxazin-4-one. yellow solid ; mp 82-
87 °C. 1H NMR (300 MHz, Chloroform-d) δ 8.34 – 8.10 (m, 2H), 8.03 (d,
J = 7.9 Hz, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.63 (dd, J = 22.9, 8.0 Hz, 1H),
7.35 – 7.22 (m, 3H), 2.66 (dt, J = 10.5, 7.6 Hz, 2H), 1.65 (pd, J = 7.3,
2.9 Hz, 2H), 1.34 (tt, J = 7.6, 3.0 Hz, 2H), 0.97 – 0.79 (m, 3H). 13C NMR
(75 MHz, CDCl3) δ 159.76, 149.56, 147.46, 136.46, 130.25, 128.79,
128.51, 128.31, 127.93, 127.54, 127.42, 127.03, 35.95, 31.42, 22.45,
13.96; IR (KBr) 2955, 2928, 2857, 1764, 1681 cm-1; HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C18H17NNaO2 302.1157; Found 302.1157.
7-Chloro-2-(4-ethylphenyl)-4H-benzo[d][1,3]oxazin-4-one.
white
solid ; mp 112-116 °C. 1H NMR (300 MHz, Chloroform-d) δ 8.22 – 7.88
(m, 4H), 7.44 (d, J = 2.1 Hz, 1H), 7.37 – 7.03 (m, 2H), 2.64 (p, J = 8.1,
7.6 Hz, 2H), 1.23 (dt, J = 10.5, 7.7 Hz, 3H). 13C NMR (75 MHz, CDCl3)
δ 158.47, 158.17, 149.77, 147.95, 142.54, 129.60, 128.38, 128.11,
127.47, 126.96, 126.64, 115.09, 28.85, 14.95; IR (KBr) 3039, 2966,
2932, 1757, 1614 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C16H13ClNO2 286.0635; Found 286.0637.
Representative experimental procedure for the olefination of 2-
phenyl-4H-benzo[d][1,3] oxazin-4-one with butyl acrylate for the
synthesis
of
(E)-butyl3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)pheny l)acryl ate (Table 2, 3a)
To a solution of 2-phenyl-4H-benzo [d][1,3] oxazin-4-one (0.5 mmol,
112 mg), K2S2O8 (0.75 mmol, 203 mg), Pd(OAc)2 (5 mol %, 11 mg),
PivOH (1 mmol, 102 mg) in dichloroethane (3 mL), n-butyl acrylate (5
mmol, 320 mg) was added. The resulting mixture was heated at 85 oC
under O2 atmosphere for 24 h (TLC). After the reaction was complete,
the mixture was allowed to cool at room temperature and was extracted
with ethyl acetate (3×20 mL) followed by washing with brine (10 mL).
The combined organic layer was dried over anhydrous Na2SO4 and
filtered. After removal of the solvent, the residue (crude product) was
purified by column chromatography over silica gel (hexane/ethyl
acetate 94:6) to afford the pure product, (E)-butyl 3-(2-(4-oxo-4H-
benzo[d][1,3]oxazin-2-yl)phenyl)acrylate as a brownish gummy liquid.
This procedure was followed for all the reactions listed in Table 2, Table
3, Table 4, Table 5 and Scheme 2. All the products were obtained in
high purity. All the products are unknown and characterized properly by
spectroscopic data (IR, 1H NMR, 13C NMR, and HR-MS). All these data
are provided in supporting information.
7,8-Dimethyl-2-phenyl-4H-benzo[d][1,3]oxazin-4-one. white solid ;
mp 166-169 °C. 1H NMR (300 MHz, Chloroform-d) δ 8.30 – 8.17 (m,
2H), 7.86 (d, J = 8.0 Hz, 1H), 7.57 – 7.34 (m, 2H), 7.17 (d, J = 8.0 Hz,
1H), 2.48 (s, 3H), 2.33 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 159.99,
155.36, 146.11, 144.56, 134.22, 132.13, 130.59, 129.55, 128.50,
128.03, 125.28, 114.50, 20.95, 12.92; IR (KBr) 3053, 2905, 1760, 1740,
1620 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H14ClNO2
252.1025; Found 252.1022.
6-Chloro-2-(thiophen-2-yl)-4H-benzo[d][1,3]oxazin-4-one.
yellow
solid ; mp 170-174 °C. 1H NMR (300 MHz, Chloroform-d) δ 8.12 (s, 1H),
7.91 (s, 1H), 7.59 (tt, J = 29.4, 15.0 Hz, 3H), 7.15 (s, 1H). 13C NMR (75
MHz, CDCl3) δ 157.85, 153.78, 145.50, 136.82, 133.74, 133.44, 132.76,
132.02, 128.37, 128.30, 127.99, 117.68; IR (KBr) 3077, 1753, 1616,
1598, 1470 cm-1; HRMS (ESI-TOF) m/z: [M
C12H7ClNO2S 263.9886; Found 263.9887.
+
H]+ Calcd for
Characterization details of the starting molecules
2-(3-(Trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-one. white
solid ; mp 129-132 °C. 1H NMR (300 MHz, Chloroform-d) δ 8.49 (s, 1H),
8.40 (d, J = 8.0 Hz, 1H), 8.17 (dd, J = 7.9, 1.7 Hz, 1H), 7.85 – 7.74 (m,
2H), 7.68 – 7.54 (m, 2H), 7.49 (td, J = 7.6, 1.3 Hz, 1H). 13C NMR (75
All together 29 benzoxazinones were prepared by this procedure. Out
of them 24 are known. They were identified by comparison of their
spectroscopic data (1H and 13C NMR) with the reported ones
(references are cited against each compound).
2
MHz, CDCl3) δ 158.79, 155.46, 146.34, 136.61, 131.31 (q, JC-F = 33
Hz), 131.18, 131.03, 129.26, 128.85 (q, 4JC-F = 3.0 Hz), 128.66, 128.56,
3
1
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one,[13a] 2-([1,1'-Biphenyl]-4-yl)-4H-
127.28, 125.05 (q, JC-F = 3.75 Hz), 123.61 (q, JC-F = 271.50 Hz),
116.94.; IR (KBr) 3079, 1761, 1626, 1602, 1574 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C15H9F3NO2 292.0585; Found 292.0583.
benzo[d][1,3]oxazin-4-one,[13b]
2-(p-Tolyl)-4H-benzo[d][1,3]oxazin-4-
one,[13a] 2-(4-Ethylphenyl)-4H-benzo[d][1,3]oxazin-4-one,[13c]
2-(m-
Tolyl)-4H-benzo[d][1,3]oxazin-4-one,[13d] 2-(4-(tert-Butyl)phenyl)-4H-ben
zo[d][1,3]oxazin-4-one,[13e] 2-(4-Methoxyphenyl)-4H-benzo[d][1,3]oxazin
-4-one,[13a] 2-(4-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one,[13b] 2-(4-
Bromophenyl)-4H-benzo[d][1,3]oxazin-4-one,[13b] 2-(4-(Trifluoromethyl)
phenyl)-4H-benzo[d][1,3]oxazin-4-one,[13a] 2-(o-Tolyl)-4H-benzo[d][1,3]
oxazin-4-one,[13f] 2-(2-(Trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-
Analytical data of the synthesized olefinic molecules
(E)-butyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)phenyl)acrylate
4-one,[13e]
7-Chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one,[13a]
7-
(Table 2, 3a). brownish gummy liquid (eluent, hexane/ethyl acetate
Chloro -2-(p-tolyl)-4H-benzo[d][1,3]oxazin-4-one,[13g] 7-Chloro-2-(4-
chloropheny l)-4H-benzo[d][1,3]oxazin-4-one,[13g] 6-Chloro-2-(p-tolyl)-
4H-benzo[d] [1,3]oxazin-4-one,[13h] 2-Phenyl-7-(trifluoromethyl)-4H-
1
(94:6), (138 mg, 79%). H NMR (500 MHz, Chloroform-d) δ 8.64 (dd, J
= 15.9, 1.7 Hz, 1H), 8.25 (d, J = 7.9 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H),
7.83 (t, J = 7.7 Hz, 1H), 7.70 (dd, J = 11.1, 8.0 Hz, 2H), 7.60 – 7.44 (m,
3H), 6.37 (dd, J = 15.8, 1.8 Hz, 1H), 4.22 (td, J = 6.7, 1.8 Hz, 2H), 1.79
– 1.51 (m, 2H), 1.43 (hd, J = 7.4, 1.8 Hz, 2H), 0.94 (td, J = 7.4, 1.8 Hz,
3H). 13C NMR (125 MHz, CDCl3) δ 166.95, 159.43, 156.55, 146.51,
144.16, 136.80, 136.07, 132.12, 130.35, 129.79, 129.01, 128.65,
128.51, 127.69, 120.79, 116.89, 100.12, 64.61, 30.95, 19.39, 13.88; IR
(KBr) 2954, 2924, 2853, 1730, 1596 cm-1; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C21H20NO4 350.1392; Found 350.1393.
benzo[d][1,3]
oxazin-4-one,[13i]
6,7-Dimethoxy-2-(p-tolyl)-4H-
8-Methyl-2-phenyl-4H-
benzo[d][1,3]oxazin-4-one,[13j]
benzo[d][1,3]oxazin-4-one,[13a]
2-(Thiop
hen-2-yl)-4H-
benzo[d][1,3]oxazin-4-one,[13a] 2-(Furan-2-yl)-4H-benzo[d][1,3]oxazin-4-
one,[13a] 2-(3-Methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one,[13b] 2-(3-
Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one,[13c]
4H-benzo[d][1,3]oxazin-4-one.[13k]
2-(3-Bromophenyl)-
The new benzoxazinones were characterized by their satisfactory IR,
1H NMR, 13C NMR and HRMS data which are provided below.
(E)-Butyl
3-(5-methyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3b). white solid ; mp 80-85 °C. eluent,
hexane/ethyl acetate (94:6), (137 mg, 76%). 1H NMR (300 MHz,
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
FULL PAPER
Chloroform-d) δ 8.68 (d, J = 15.9 Hz, 1H), 8.24 (dd, J = 7.9, 1.5 Hz, 1H),
8.04 (d, J = 8.1 Hz, 1H), 7.86 – 7.77 (m, 1H), 7.69 (dd, J = 8.1, 1.2 Hz,
1H), 7.57 – 7.43 (m, 2H), 7.32 (dd, J = 8.2, 1.7 Hz, 1H), 6.36 (d, J =
15.9 Hz, 1H), 4.23 (t, J = 6.6 Hz, 2H), 2.44 (s, 3H), 1.70 (dq, J = 8.3,
6.6 Hz, 2H), 1.51 – 1.37 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H).13C NMR (75
MHz, CDCl3) δ 167.08, 159.57, 156.60, 146.65, 144.56, 142.78, 136.71,
136.09, 130.59, 130.36, 129.21, 128.74, 128.57, 127.58, 126.91,
120.45, 116.80, 64.58, 30.95, 21.66, 19.38, 13.87; IR (KBr) 2919, 2854,
1715, 1602 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22NO4
364.1549; Found 364.1549.
113.97, 64.63, 55.75, 30.97, 19.39, 13.89; IR (KBr) 2959, 2930, 2872,
1759, 1709 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22NO5
380.1498; Found 380.1494.
(E)-Butyl 3-(4-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-[1,1'-biphenyl]-3-
yl)acrylate (Table 2, 3g). white solid ; mp 107-109 °C. eluent,
hexane/ethyl acetate (94:6), (161 mg, 76%). 1H NMR (300 MHz,
Chloroform-d) δ 8.77 (d, J = 15.9 Hz, 1H), 8.31 – 8.18 (m, 2H), 7.94 –
7.79 (m, 2H), 7.78 – 7.70 (m, 2H), 7.70 – 7.61 (m, 2H), 7.61 – 7.35 (m,
4H), 6.44 (d, J = 15.9 Hz, 1H), 4.26 (t, J = 6.6 Hz, 2H), 1.81 – 1.65 (m,
2H), 1.53 – 1.37 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 166.92, 159.41, 156.41, 146.63, 144.94, 144.57, 139.38,
136.78, 136.75, 130.90, 129.19, 128.90, 128.65, 128.22, 127.70,
127.36, 127.23, 125.32, 124.43, 120.95, 116.92, 64.63, 30.99, 19.40,
13.88; IR (KBr) 3068, 2952, 1778, 1628, 1603 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C27H24NO4 426.1705; Found 426.1707.
(E)-Butyl
3-(5-ethyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3c). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (143 mg, 76%). 1H NMR (300 MHz,
Chloroform-d) δ 8.69 (d, J = 15.9 Hz, 1H), 8.25 (dd, J = 7.9, 1.5 Hz, 1H),
8.07 (d, J = 8.1 Hz, 1H), 7.83 (ddd, J = 8.6, 7.3, 1.6 Hz, 1H), 7.70 (dd, J
= 8.2, 1.2 Hz, 1H), 7.64 – 7.44 (m, 2H), 7.36 (dd, J = 8.1, 1.8 Hz, 1H),
6.38 (d, J = 15.8 Hz, 1H), 4.24 (t, J = 6.6 Hz, 2H), 2.75 (q, J = 7.6 Hz,
2H), 1.70 (dq, J = 8.4, 6.7 Hz, 2H), 1.54 – 1.37 (m, 2H), 1.30 (t, J = 7.6
Hz, 3H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 167.10,
159.61, 156.64, 148.96, 146.68, 144.69, 136.74, 136.20, 130.48,
129.45, 128.76, 128.60, 128.08, 127.61, 127.13, 120.44, 116.83, 64.59,
30.96, 27.13, 19.39, 15.25, 13.89; IR (KBr) 2961, 2932, 2873, 1708,
1618 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H24NO4
378.1705; Found 378.1702.
(E)-Butyl
3-(5-chloro-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3h). white solid ; mp 70-72 °C. eluent,
hexane/ethyl acetate (94:6), (143 mg, 75%). 1H NMR (300 MHz,
Chloroform-d) δ 8.63 (d, J = 15.9 Hz, 1H), 8.31 – 8.23 (m, 1H), 8.11 (d,
J = 8.5 Hz, 1H), 7.85 (ddd, J = 8.1, 7.3, 1.6 Hz, 1H), 7.76 – 7.63 (m,
2H), 7.63 – 7.45 (m, 2H), 6.36 (d, J = 15.8 Hz, 1H), 1.75 – 1.64 (m, 2H),
1.52 – 1.36 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, CDCl3)
δ 166.60, 159.16, 155.68, 146.37, 143.07, 138.51, 137.94, 136.89,
131.66, 129.76, 129.18, 128.71, 128.63, 127.93, 127.73, 121.84,
116.87, 64.76, 30.93, 19.38, 13.87; IR (KBr) 2959, 2873, 1699, 1601
cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H19ClNO4 384.1003;
Found 384.1005.
(E)-Butyl
3-(5-butyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3d). brownish solid ; mp 52-54 °C. eluent,
hexane/ethyl acetate (94:6), (135 mg, 66%). 1H NMR (300 MHz,
Chloroform-d) δ 8.68 (d, J = 15.9 Hz, 1H), 8.24 (dd, J = 7.9, 1.5 Hz, 1H),
8.06 (d, J = 8.1 Hz, 1H), 7.89 – 7.76 (m, 1H), 7.70 (dd, J = 8.1, 1.2 Hz,
1H), 7.52 (ddd, J = 14.4, 7.0, 1.5 Hz, 2H), 7.33 (dd, J = 8.2, 1.8 Hz, 1H),
6.37 (d, J = 15.8 Hz, 1H), 4.24 (t, J = 6.6 Hz, 2H), 2.70 (t, J = 7.7 Hz,
2H), 1.78 – 1.55 (m, 5H), 1.55 – 1.30 (m, 4H), 0.95 (td, J = 7.3, 1.4 Hz,
5H).13C NMR (75 MHz, CDCl3) δ 167.03, 159.55, 156.62, 147.71,
146.63, 144.62, 136.70, 136.06, 130.36, 129.96, 128.73, 128.57,
127.57, 127.06, 125.15, 120.39, 116.78, 64.54, 35.70, 33.29, 30.94,
22.43, 19.37, 14.01, 13.87; IR (KBr) 2957, 2929, 2871, 1763, 1602 cm-
1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H28NO4 406.2018;
Found 406.2018.
(E)-Butyl
3-(5-bromo-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3i). white solid ; mp 66-71 °C. eluent,
hexane/ethyl acetate (94:6), (162 mg, 76%). 1H NMR (300 MHz,
Chloroform-d) δ 8.62 (d, J = 15.9 Hz, 1H), 8.35 – 8.18 (m, 1H), 8.03 (d,
J = 8.5 Hz, 1H), 7.90 – 7.79 (m, 2H), 7.68 (ddd, J = 16.8, 8.3, 1.6 Hz,
2H), 7.62 – 7.51 (m, 1H), 6.36 (d, J = 15.8 Hz, 1H), 4.24 (t, J = 6.6 Hz,
2H), 1.76 – 1.62 (m, 2H), 1.45 (ddt, J = 14.5, 9.5, 7.4 Hz, 2H), 0.96 (t, J
= 7.4 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 166.58, 159.15, 155.77,
146.35, 143.00, 138.02, 136.90, 132.73, 131.68, 131.57, 129.20,
128.72, 128.35, 127.74, 126.96, 121.85, 116.87, 64.76, 30.92, 19.38,
13.88; IR (KBr) 2959, 2929, 2872, 1766, 1714 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C21H19BrNO4 428.0497; Found 428.0497.
(E)-Butyl
3-(5-(tert-butyl)-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3e). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (135 mg, 67%). 1H NMR (300 MHz,
Chloroform-d) δ 8.70 (d, J = 15.9 Hz, 1H), 8.25 (dd, J = 7.9, 1.5 Hz, 1H),
8.08 (d, J = 8.3 Hz, 1H), 7.83 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.75 –
7.64 (m, 2H), 7.61 – 7.49 (m, 2H), 6.38 (d, J = 15.8 Hz, 1H), 4.25 (t, J =
6.6 Hz, 2H), 1.71 (dq, J = 8.5, 6.7 Hz, 2H), 1.45 (q, J = 7.4 Hz, 2H),
1.38 (s, 9H), 0.95 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
185.05, 167.12, 159.60, 155.82, 146.66, 145.06, 136.72, 135.85,
130.23, 128.76, 128.59, 127.61, 127.02, 126.87, 125.57, 120.32,
116.83, 64.61, 38.67, 35.29, 31.17, 30.96, 27.11, 19.39, 13.89; IR (KBr)
2959, 2871, 1678, 1638, 1604 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C25H28NO4 406.2018; Found 406.2011.
(E)-Butyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
(trifluoromethyl)phenyl)acrylate (Table 2, 3j). brownish liquid. eluent,
hexane/ethyl acetate (94:6), (143 mg, 69%). 1H NMR (300 MHz,
Chloroform-d) δ 8.65 (d, J = 15.9 Hz, 1H), 8.37 – 8.20 (m, 2H), 8.04 –
7.81 (m, 2H), 7.75 (ddd, J = 9.4, 8.1, 1.4 Hz, 2H), 7.66 – 7.53 (m, 1H),
6.43 (d, J = 15.9 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 1.79 – 1.59 (m, 2H),
1.45 (dp, J = 9.6, 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H). 13C NMR (75
MHz, CDCl3) δ 184.76, 166.52, 158.94, 155.31, 146.14, 142.90, 137.00,
2
133.80(q, JC-F = 43.0 Hz), 132.64, 130.93, 129.57, 128.79, 127.90,
126.20 (q, JC-F = 3.75 Hz), 125.47 (q, 3JC-F = 4.50 Hz), 122.31, 116.99,
4
114.99 (q, JC-F = 234.75 Hz), 100.13, 64.86, 27.13, 19.37, 13.87. 19
F
1
NMR (376 MHz, CDCl3) δ -162.39; IR (KBr) 2960, 2932, 2874, 1768,
1714 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H18F3NNaO4
440.1086; Found 440.1084.
(E)-Butyl
3-(5-methoxy-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3f). yellow solid ; mp 91-93 °C. eluent,
hexane/ethyl acetate (93:7), (153 mg, 81%). 1H NMR (300 MHz,
Chloroform-d) δ 8.73 (d, J = 15.8 Hz, 1H), 8.23 (ddd, J = 7.9, 1.6, 0.6
Hz, 1H), 8.14 (d, J = 8.9 Hz, 1H), 7.81 (ddd, J = 8.1, 7.3, 1.6 Hz, 1H),
7.67 (ddd, J = 8.1, 1.2, 0.6 Hz, 1H), 7.52 (ddd, J = 7.8, 7.2, 1.2 Hz, 1H),
7.14 (d, J = 2.6 Hz, 1H), 7.02 (dd, J = 8.8, 2.6 Hz, 1H), 6.34 (d, J = 15.8
Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 3.91 (s, 3H), 1.77 – 1.60 (m, 2H), 1.53
– 1.37 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
166.95, 162.43, 159.66, 156.35, 146.83, 144.73, 138.39, 136.69,
132.31, 128.57, 128.48, 127.46, 121.95, 120.74, 116.67, 115.11,
(E)-Butyl
3-(3-methyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3k). yellowish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (96 mg, 53%). 1H NMR (400 MHz,
Chloroform-d) δ 8.40 – 8.23 (m, 1H), 7.88 (s, 1H), 7.72 (d, J = 3.0 Hz,
1H), 7.67 – 7.51 (m, 3H), 7.42 (s, 1H), 7.33 (d, J = 7.6 Hz, 1H), 6.42 (d,
J = 15.8 Hz, 1H), 4.12 (t, J = 6.5 Hz, 2H), 2.40 (s, 3H), 1.58 (dd, J = 8.4,
6.2 Hz, 2H), 1.31 (dd, J = 15.1, 7.6 Hz, 2H), 0.85 (t, J = 7.5 Hz, 3H). 13
NMR (101 MHz, CDCl3) δ 146.16, 141.49, 138.76, 137.81, 136.93,
C
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
FULL PAPER
134.10, 133.39, 132.10, 130.94, 130.66, 129.37, 128.81, 127.97,
127.54, 124.42, 121.44, 120.02, 64.59, 30.78, 30.57, 19.29, 13.77; IR
(KBr) 2963, 2927, 2853, 1770, 1724 cm-1; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H22NO4 364.1549; Found 364.1549.
143.39, 142.84, 138.95, 138.20, 131.77, 129.98, 129.77, 129.69,
128.77, 127.43, 122.09, 115.24, 64.82, 30.95, 19.38, 13.85; IR (KBr)
3082, 2960, 2929, 2873, 1773 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C21H19Cl2NO4 440.0432; Found 440.0431.
(E)-Butyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-3-
(E)-Butyl
3-(2-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
(trifluoromethyl)phenyl)acrylate (Table 2, 3l). yellowish gummy liquid.
eluent, hexane/ethyl acetate (94:6), (118 mg, 57%). 1H NMR (300 MHz,
Chloroform-d) δ 8.30 (dd, J = 7.9, 1.5 Hz, 1H), 7.95 – 7.85 (m, 2H),
7.82 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 2.6 Hz, 1H), 7.69 – 7.60 (m, 3H),
6.47 (d, J = 15.8 Hz, 1H), 4.12 (t, J = 6.5 Hz, 2H), 1.64 – 1.49 (m, 2H),
1.35 – 1.26 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H).13C NMR (75 MHz, CDCl3)
δ 165.90, 158.61, 155.21, 145.77, 139.32, 137.05, 135.54, 130.99,
methylphenyl)acrylate (Table 2, 3q). yellowish liquid. eluent,
hexane/ethyl acetate (94:6), (125 mg, 63%).1H NMR (300 MHz,
Chloroform-d) δ 8.66 (d, J = 15.9 Hz, 1H), 8.21 (d, J = 2.4 Hz, 1H), 8.05
(d, J = 8.1 Hz, 1H), 7.76 (dd, J = 8.6, 2.4 Hz, 1H), 7.65 (d, J = 8.6 Hz,
1H), 7.49 (t, J = 1.3 Hz, 1H), 7.39 – 7.29 (m, 1H), 6.35 (d, J = 15.8 Hz,
1H), 4.24 (t, J = 6.6 Hz, 2H), 2.46 (s, 3H), 1.80 – 1.58 (m, 2H), 1.54 –
1.34 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H).13C NMR (101 MHz, CDCl3) δ
166.99, 158.46, 156.85, 145.21, 144.49, 143.16, 137.01, 136.36,
134.42, 130.63, 130.44, 129.38, 129.17, 127.99, 126.51, 120.69,
117.97, 64.60, 31.00, 21.70, 19.40, 13.89; IR (KBr) 2958, 2928, 2872,
2
130.39, 130.06(q, JC-F = 6.0 Hz), 129.75, 129.54, 128.97, 127.83 (q,
1
3JC-F = 3.0 Hz), 127.64, 123.61, 123.39 (q, JC-F = 272 Hz) , 117.03,
64.86, 30.67, 19.23, 13.76. 19F NMR (376 MHz, CDCl3) δ -159.11. IR
(KBr) 2963, 2919, 2850, 1767, 1717 cm-1; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H19F3NO4 418.1266; Found 418.1262.
1761, 1711 cm-1; HRMS (ESI-TOF) m/z: [M
C22H21ClNO4 398.1159; Found 398.1152.
+
H]+ Calcd for
(E)-Butyl
3-(2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
(E)-Butyl 3-(2-(4-oxo-7-(trifluoromethyl)-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3r). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (152 mg, 73%). 1H NMR (300 MHz,
Chloroform-d) δ 8.63 (d, J = 15.9 Hz, 1H), 8.39 (d, J = 8.2 Hz, 1H), 8.20
– 8.13 (m, 1H), 7.97 (d, J = 1.7 Hz, 1H), 7.79 (dd, J = 8.8, 1.5 Hz, 1H),
7.74 – 7.68 (m, 1H), 7.58 (ddd, J = 10.9, 7.5, 1.6 Hz, 2H), 6.38 (d, J =
15.9 Hz, 1H), 4.25 (t, J = 6.7 Hz, 2H), 1.77 – 1.64 (m, 2H), 1.50 – 1.36
(m, 2H), 0.95 (t, J = 7.3 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 166.76,
yl)phenyl)acrylate (Table 2, 3m). brownish solid ; mp 104-107 °C.
eluent, hexane/ethyl acetate (94:6), (124 mg, 65%). 1H NMR (300 MHz,
Chloroform-d) δ 8.63 (d, J = 15.9 Hz, 1H), 8.23 – 8.09 (m, 2H), 7.70 (dd,
J = 8.0, 1.7 Hz, 2H), 7.65 – 7.44 (m, 3H), 6.37 (d, J = 15.8 Hz, 1H),
4.25 (t, J = 6.6 Hz, 2H), 1.79 – 1.64 (m, 2H), 1.53 – 1.33 (m, 2H), 0.97
(t, J = 7.4 Hz, 3H).13C NMR (100 MHz, CDCl3) δ 166.86, 158.60,
157.82, 147.62, 143.99, 143.31, 136.41, 132.49, 130.49, 129.96,
129.80, 129.55, 129.30, 128.66, 127.43, 121.10, 115.31, 64.69, 31.00,
19.40, 13.86; IR (KBr) 2959, 2929, 2867, 1766, 1712 cm-1; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C21H19ClNO4 384.1003; Found 384.1003.
2
158.25, 157.90, 146.90, 143.79, 138.35 (q, JC-F = 33.0 Hz), 136.54,
4
132.69, 130.55, 129.84, 129.73, 129.06, 128.75, 125.15 (q, JC-F = 3.0
3
1
Hz), 124.99 (q, JC-F = 4.0 Hz), 123.11(q, JC-F = 273 Hz), 121.35,
119.50, 64.74, 30.96, 19.34, 13.77. 19F NMR (376 MHz, CDCl3) δ -
163.41; IR (KBr) 2960, 2928, 2870, 1773, 1713 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C22H19F3NO4 418.1266; Found 418.1268.
(E)-butyl
3-(2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
methylphenyl)acrylate (Table 2, 3n). white solid ; mp 111-114 °C.
eluent, hexane/ethyl acetate (94:6), (143 mg, 72%). 1H NMR (300 MHz,
Chloroform-d) δ 8.65 (d, J = 15.9 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.05
(d, J = 8.1 Hz, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.52 – 7.46 (m, 2H), 7.36 –
7.30 (m, 1H), 6.35 (d, J = 15.9 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 2.46 (s,
3H), 1.79 – 1.63 (m, 2H), 1.54 – 1.35 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H).
13C NMR (126 MHz, CDCl3) δ 166.91, 158.71, 157.95, 147.83, 144.35,
143.29, 143.22, 136.54, 130.59, 130.55, 129.92, 129.40, 129.28,
127.35, 126.53, 120.86, 115.31, 64.64, 31.05, 21.69, 19.42, 13.86; IR
(KBr) 2959, 2926, 2854, 1779, 1715 cm-1; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H21ClNO4 398.1159; Found 398.1147.
(E)-Butyl 3-(2-(6,7-dimethoxy-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
methylphenyl)acrylate (Table 2, 3s). yellowish liquid. eluent,
hexane/ethyl acetate (90:10), (148 mg, 70%). 1H NMR (300 MHz,
Chloroform-d) δ 8.62 (d, J = 15.9 Hz, 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.57
(s, 1H), 7.50 (d, J = 1.7 Hz, 1H), 7.33 (dt, J = 8.3, 1.2 Hz, 1H), 7.10 (s,
1H), 6.38 (d, J = 15.9 Hz, 1H), 4.22 (t, J = 6.7 Hz, 2H), 4.03 (s, 3H),
4.01 (s, 3H), 2.45 (s, 3H), 1.70 (tt, J = 8.5, 6.5 Hz, 2H), 1.52 – 1.35 (m,
2H), 0.94 (t, J = 7.3 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 167.03,
159.52, 156.80, 156.33, 150.31, 144.45, 143.17, 142.39, 135.78,
130.62, 130.32, 129.11, 127.51, 120.55, 109.58, 108.56, 107.79, 64.55,
56.67, 31.06, 29.86, 21.64, 19.41, 13.86; IR (KBr) 2961, 2925, 2854,
1752, 1711 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H26NO6
424.1760; Found 424.1761.
(E)-Butyl
3-(2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
ethylphenyl)acrylate (Table 2, 3o). white solid ; mp 77-80 °C. eluent,
hexane/ethyl acetate (94:6), (139 mg, 68%). 1H NMR (300 MHz,
Chloroform-d) δ 8.65 (d, J = 15.8 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.05
(d, J = 8.1 Hz, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.48 (dd, J = 8.4, 2.0 Hz,
2H), 7.34 (dd, J = 8.2, 1.8 Hz, 1H), 6.34 (d, J = 15.9 Hz, 1H), 4.25 (t, J
= 6.6 Hz, 2H), 2.74 (q, J = 7.6 Hz, 2H), 1.78 – 1.65 (m, 2H), 1.46 (dp, J
(E)-Butyl
3-(2-(8-methyl-4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3t). brownish solid ; mp 66 - 68 °C. eluent,
hexane/ethyl acetate (94:6), (78 mg, 43%). 1H NMR (300 MHz,
Chloroform-d) δ 8.71 (d, J = 16.0 Hz, 1H), 8.25 – 8.17 (m, 1H), 8.11
(ddd, J = 7.9, 1.6, 0.7 Hz, 1H), 7.72 – 7.64 (m, 2H), 7.61 – 7.50 (m, 2H),
7.44 (t, J = 7.7 Hz, 1H), 6.37 (d, J = 15.8 Hz, 1H), 4.23 (t, J = 6.7 Hz,
2H), 2.61 (s, 3H), 1.73 – 1.65 (m, 2H), 1.51 – 1.36 (m, 2H), 0.95 (t, J =
7.3 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 166.94, 159.96, 155.04,
145.19, 137.60, 137.10, 136.63, 132.03, 130.25, 129.83, 129.74,
128.93, 128.41, 127.81, 126.20, 120.53, 116.94, 64.59, 31.03, 29.85,
22.83, 19.36, 17.49, 13.85; IR (KBr) 2958, 2926, 2872, 1760, 1710 cm-
1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22NO4 364.1549;
Found 364.1549.
= 9.5, 7.3 Hz, 2H), 1.34 – 1.19 (m, 3H), 0.96 (t, J = 7.4 Hz, 3H).13
C
NMR (126 MHz, CDCl3) δ 166.91, 158.71, 157.78, 149.40, 147.70,
144.45, 143.13, 136.47, 130.58, 129.86, 129.41, 129.24, 128.20,
127.27, 126.55, 120.65, 115.18, 64.60, 30.96, 28.97, 19.38, 15.17,
13.86; IR (KBr) 2961, 2930, 2873, 1763, 1711 cm-1; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C23H23ClNO4 412.1316; Found 412.1312.
(E)-Butyl 3-(5-chloro-2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3p). white solid ; mp 139-141 °C. eluent,
hexane/ethyl acetate (94:6), (127 mg, 61%). 1H NMR (400 MHz,
Chloroform-d) δ 8.59 (d, J = 15.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.10
(d, J = 8.5 Hz, 1H), 7.67 (dd, J = 16.1, 2.1 Hz, 2H), 7.51 (ddd, J = 10.1,
8.5, 2.1 Hz, 2H), 6.35 (d, J = 15.8 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 1.72
(dd, J = 8.5, 6.2 Hz, 2H), 1.46 (q, J = 7.5 Hz, 2H), 0.97 (t, J = 7.4 Hz,
3H).13C NMR (101 MHz, CDCl3) δ 166.47, 158.30, 156.91, 147.42,
(E)-Butyl
3-(2-(7,8-dimethyl-4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 2, 3u). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (75 mg, 40%).1H NMR (300 MHz,
Chloroform-d) δ 8.68 (d, J = 15.9 Hz, 1H), 8.27 – 8.13 (m, 1H), 8.02 (d,
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
FULL PAPER
J = 8.0 Hz, 1H), 7.75 – 7.62 (m, 1H), 7.62 – 7.46 (m, 2H), 7.35 (d, J =
8.0 Hz, 1H), 6.38 (d, J = 15.8 Hz, 1H), 4.23 (t, J = 6.7 Hz, 2H), 2.53 (s,
3H), 2.46 (s, 3H), 1.81 – 1.64 (m, 2H), 1.50 – 1.34 (m, 2H), 0.95 (t, J =
7.3 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 166.94, 160.17, 154.87,
146.60, 145.28, 144.83, 136.50, 135.27, 131.88, 130.47, 130.23,
130.14, 129.72, 128.88, 125.55, 120.44, 114.70, 64.56, 31.05, 21.22,
19.36, 13.85, 13.47; IR (KBr) 2958, 2929, 2872, 1751, 1711 cm-1;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H24NO4 378.1705; Found
378.1706.
Chloroform-d) δ 8.63 (d, J = 15.8 Hz, 1H), 8.26 (dd, J = 7.8, 1.5 Hz, 1H),
8.03 (d, J = 8.5 Hz, 1H), 7.90 – 7.76 (m, 2H), 7.69 (ddd, J = 15.7, 8.4,
1.7 Hz, 2H), 7.58 (ddd, J = 8.1, 7.4, 1.3 Hz, 1H), 6.36 (d, J = 15.8 Hz,
1H), 3.84 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 166.96, 159.12, 155.79,
146.39, 143.47, 138.00, 136.94, 132.80, 131.70, 131.62, 129.21,
128.73, 128.43, 127.79, 126.98, 121.33, 116.91, 52.01; IR (KBr) 2923,
2852, 1776, 1621, 1602 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C18H13BrNO4 386.0028; Found 386.0024.
(E)-Methyl
3-(2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
(E)-Methyl 3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)phenyl)acrylate
(Table 3, 4a). white solid ; mp 133-136 °C. eluent, hexane/ethyl acetate
(94:6), (113 mg, 74%). 1H NMR (300 MHz, Chloroform-d) δ 8.66 (d, J =
15.9 Hz, 1H), 8.26 (ddd, J = 7.9, 1.6, 0.6 Hz, 1H), 8.19 – 8.08 (m, 1H),
7.85 (ddd, J = 8.1, 7.3, 1.5 Hz, 1H), 7.77 – 7.64 (m, 2H), 7.62 – 7.50 (m,
3H), 6.38 (d, J = 15.9 Hz, 1H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 167.33, 159.43, 156.55, 146.55, 144.65, 136.86, 136.05, 132.14,
130.38, 129.86, 129.82, 129.02, 128.67, 128.55, 127.74, 120.27,
116.91, 51.91; IR (KBr) 2951, 2924, 2850, 1781, 1766 cm-1; HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C18H14NO4 308.0923; Found
308.0923.
yl)phenyl)acrylate (Table 3, 4f). blackish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (110 mg, 65%). 1H NMR (300 MHz,
Chloroform-d) δ 8.62 (d, J = 15.9 Hz, 1H), 8.24 – 8.08 (m, 2H), 7.75 –
7.64 (m, 2H), 7.64 – 7.44 (m, 3H), 6.37 (d, J = 15.8 Hz, 1H), 3.85 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 167.24, 158.62, 157.79, 147.60,
144.43, 143.33, 136.26, 132.50, 130.50, 129.95, 129.88, 129.58,
129.37, 128.69, 127.46, 120.51, 115.27, 51.97; IR (KBr) 2918, 2853,
1766, 1719, 1598 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C18H12ClNaO4 364.0353; Found 364.0353.
(E)-Methyl 3-(5-chloro-2-(7-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 3, 4g). white solid ; mp 172-175 °C. eluent,
hexane/ethyl acetate (94:6), (127 mg, 68%). 1H NMR (300 MHz,
Chloroform-d) δ 8.59 (d, J = 15.8 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 8.10
(d, J = 8.5 Hz, 1H), 7.66 (dd, J = 16.3, 2.0 Hz, 2H), 7.51 (ddd, J = 8.4,
6.1, 2.1 Hz, 2H), 6.35 (d, J = 15.8 Hz, 1H), 3.85 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 166.87, 158.31, 156.89, 147.41, 143.42, 143.30, 138.94,
138.08, 131.79, 129.98, 129.84, 129.72, 128.79, 127.50, 127.47,
121.51, 115.21, 52.07; IR (KBr) 3089, 2922, 2852, 1774, 1723 cm-1;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H12Cl2NO4 376.0143;
Found 376.0143.
(E)-Methyl
3-(5-ethyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 3, 4b). blakish solid ; mp 122-126 °C. eluent,
hexane/ethyl acetate (94:6), (122 mg, 73%).1H NMR (300 MHz,
Chloroform-d) δ 8.69 (d, J = 15.9 Hz, 1H), 8.25 (dd, J = 7.9, 1.5 Hz, 1H),
8.07 (d, J = 8.1 Hz, 1H), 7.83 (ddd, J = 8.1, 7.3, 1.6 Hz, 1H), 7.75 –
7.63 (m, 1H), 7.63 – 7.43 (m, 2H), 7.36 (dd, J = 8.2, 1.8 Hz, 1H), 6.37
(d, J = 15.9 Hz, 1H), 3.83 (s, 3H), 2.75 (q, J = 7.6 Hz, 2H), 1.38 – 1.16
(m, 3H). 13C NMR (101 MHz, CDCl3) δ 167.40, 159.56, 156.62, 148.98,
146.69, 145.12, 136.77, 136.17, 130.49, 129.48, 128.76, 128.59,
128.10, 127.65, 127.17, 119.92, 116.84, 51.86, 28.97, 15.22.; IR (KBr)
2963, 2928, 2853, 1763, 1719 cm-1; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C20H17NNaO4 358.1055; Found 358.1057.
(E)-Methyl
3-(2-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-5-
methylphenyl)acrylate (Table 3, 4h). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (111 mg, 63%).1H NMR (300 MHz,
Chloroform-d) δ 8.66 (d, J = 15.8 Hz, 1H), 8.20 (dd, J = 2.4, 0.5 Hz, 1H),
8.05 (d, J = 8.1 Hz, 1H), 7.76 (dd, J = 8.6, 2.4 Hz, 1H), 7.65 (dd, J = 8.6,
0.5 Hz, 1H), 7.51 – 7.42 (m, 1H), 7.40 – 7.29 (m, 1H), 6.35 (d, J = 15.9
Hz, 1H), 3.83 (s, 3H), 2.46 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 167.38,
158.48, 156.75, 145.16, 144.97, 143.18, 137.07, 136.24, 134.40,
130.69, 130.41, 129.40, 129.20, 127.96, 126.48, 120.06, 117.91, 51.91,
21.71; IR (KBr) 2919, 2850, 1777, 1723, 1621 cm-1; HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C19H14ClNNaO4 378.0509; Found 378.0508.
(E)-methyl
3-(5-butyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 3, 4c). yellow gummy liquid. eluent,
hexane/ethyl acetate (94:6), (136 mg, 75%). 1H NMR (300 MHz,
Chloroform-d) δ 8.68 (d, J = 15.9 Hz, 1H), 8.24 (ddd, J = 7.9, 1.6, 0.6
Hz, 1H), 8.05 (d, J = 8.1 Hz, 1H), 7.82 (ddd, J = 8.1, 7.2, 1.5 Hz, 1H),
7.69 (ddd, J = 8.1, 1.2, 0.5 Hz, 1H), 7.53 (ddd, J = 7.9, 7.2, 1.2 Hz, 1H),
7.47 (d, J = 1.7 Hz, 1H), 7.33 (dd, J = 8.1, 1.8 Hz, 1H), 6.36 (d, J = 15.9
Hz, 1H), 3.83 (s, 3H), 2.69 (t, J = 7.7 Hz, 2H), 1.64 (tt, J = 9.0, 7.5 Hz,
2H), 1.46 – 1.31 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 184.52, 167.40, 159.54, 156.62, 147.74, 146.67, 145.11,
136.75, 136.05, 130.38, 130.00, 128.73, 128.57, 127.62, 127.12,
119.88, 116.80, 51.85, 35.69, 27.11, 22.43, 14.00; IR (KBr) 2955, 2934,
2866, 1763, 1719 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H22NO4 364.1549; Found 364.1549.
(E)-Methyl 3-(2-(4-oxo-7-(trifluoromethyl)-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 3, 4i). brownish solid ; mp 131-134 °C.
eluent, hexane/ethyl acetate (94:6), (140 mg, 75%).1H NMR (300 MHz,
Chloroform-d) δ 8.61 (d, J = 15.9 Hz, 1H), 8.45 – 8.32 (m, 1H), 8.15 (dd,
J = 7.8, 1.5 Hz, 1H), 7.96 (dt, J = 1.6, 0.8 Hz, 1H), 7.77 (ddd, J = 8.2,
1.7, 0.7 Hz, 1H), 7.72 – 7.64 (m, 1H), 7.64 – 7.48 (m, 2H), 6.37 (d, J =
15.9 Hz, 1H), 3.84 (s, 3H).13C NMR (100 MHz, CDCl3) δ 167.11, 158.21,
(E)-Methyl
3-(5-chloro-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
2
yl)phenyl)acrylate (Table 3, 4d). yellow solid ; mp 167-172 °C. eluent,
hexane/ethyl acetate (94:6), (115 mg, 68%).1H NMR (300 MHz,
Chloroform-d) δ 8.63 (d, J = 15.8 Hz, 1H), 8.24 (ddd, J = 7.9, 1.6, 0.5
Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.84 (ddd, J = 8.1, 7.3, 1.6 Hz, 1H),
7.70 (ddd, J = 8.1, 1.3, 0.5 Hz, 1H), 7.63 (d, J = 2.2 Hz, 1H), 7.56 (ddd,
J = 7.9, 7.3, 1.2 Hz, 1H), 7.49 (dd, J = 8.5, 2.2 Hz, 1H), 6.35 (d, J =
15.8 Hz, 1H), 3.84 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 166.94,
159.10, 155.62, 146.35, 143.52, 138.50, 137.87, 136.91, 131.65,
129.79, 129.16, 128.69, 128.64, 127.93, 127.75, 121.25, 116.85, 52.00;
IR (KBr) 2950, 2925, 2847, 1767, 1724 cm-1; HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C18H13ClNO4 342.0533; Found 342.0531.
157.86, 146.86, 144.21, 138.31 (q, JC-F = 33.0 Hz), 136.39, 132.66,
4
130.54, 129.87, 129.69, 129.12, 128.72, 125.15 (q, JC-F = 3.0 Hz),
3
1
125.0 (q, JC-F = 4.0 Hz), 123.08 (q, JC-F = 272.0 Hz), 120.72, 119.45,
51.92. 19F NMR (376 MHz, CDCl3) δ -163.62. IR (KBr) 2950, 2918,
2853, 1772, 1718 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C19H13F3NO4 376.0797; Found 376.0799.
(E)-Butyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)thiophen-3-
mp 62-64 °C. eluent,
yl)acrylate (Table 4, 5a). yellow solid
;
hexane/ethyl acetate (93:7), (113 mg, 64%).1H NMR (300 MHz,
Chloroform-d) δ 8.90 (dd, J = 16.1, 0.7 Hz, 1H), 8.21 (ddt, J = 7.9, 1.5,
0.7 Hz, 1H), 7.81 (dddd, J = 8.0, 7.2, 1.5, 0.6 Hz, 1H), 7.73 – 7.63 (m,
1H), 7.59 – 7.45 (m, 2H), 7.42 (dt, J = 5.3, 0.6 Hz, 1H), 6.42 (dd, J =
16.2, 0.7 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 1.84 – 1.62 (m, 2H), 1.62 –
1.38 (m, 2H), 0.99 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
(E)-Methyl
3-(5-bromo-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 3, 4e). white solid ; mp 170-173 °C. eluent,
hexane/ethyl acetate (94:6), (136 mg, 71%).1H NMR (300 MHz,
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
FULL PAPER
167.11, 158.60, 153.37, 146.71, 140.58, 137.37, 136.82, 131.82,
130.72, 128.83, 128.59, 127.56, 127.45, 122.04, 116.79, 64.77, 30.92,
19.42, 13.91; IR (KBr) 3107, 2958, 2932, 2872, 1765 cm-1; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C19H18NO4S 356.0957; Found 356.0959.
116.85, 64.51, 30.95, 21.38, 19.37, 13.87; IR (KBr) 2960, 2938, 2876,
1723, 1601 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22NO4
364.1549; Found 364.1544.
(E)-Butyl
3-(4-methoxy-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
(E)-Butyl
3-(2-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 5, 6b). yellow solid ; mp 90-91 °C. eluent,
hexane/ethyl acetate (94:6), (125 mg, 66%). 1H NMR (500 MHz,
Chloroform-d) δ 8.59 (d, J = 15.8 Hz, 1H), 8.25 (dd, J = 7.9, 1.5 Hz, 1H),
7.86 – 7.80 (m, 1H), 7.72 (dd, J = 8.1, 1.1 Hz, 1H), 7.66 (d, J = 8.7 Hz,
1H), 7.59 – 7.53 (m, 2H), 7.09 (ddd, J = 8.7, 2.8, 0.6 Hz, 1H), 6.31 (d, J
= 15.9 Hz, 1H), 4.20 (t, J = 6.6 Hz, 2H), 3.90 (s, 3H), 1.72 – 1.59 (m,
2H), 1.54 – 1.34 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H).13C NMR (101 MHz,
CDCl3) δ 167.21, 160.80, 159.35, 156.43, 146.46, 143.42, 136.79,
131.27, 129.81, 129.04, 128.65, 128.33, 127.73, 118.96, 118.52,
116.94, 114.82, 64.46, 55.86, 30.98, 19.38, 13.86; IR (KBr) 2958, 2932,
2873, 1760, 1707 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H22NO5 380.1498; Found 380.1496.
yl)thiophen-3-yl)acrylate (Table 4, 5b). yellow solid ; mp 72-75 °C.
eluent, hexane/ethyl acetate (93:7), (116 mg, 60 %). 1H NMR (300 MHz,
Chloroform-d) δ 8.88 (dt, J = 16.1, 0.6 Hz, 1H), 8.19 (dd, J = 2.5, 0.5 Hz,
1H), 7.79 – 7.72 (m, 1H), 7.65 (dd, J = 8.7, 0.5 Hz, 1H), 7.56 (dd, J =
5.3, 0.7 Hz, 1H), 7.43 (dd, J = 5.3, 0.5 Hz, 1H), 6.44 (d, J = 16.1 Hz,
1H), 4.30 – 4.21 (m, 2H), 1.80 – 1.67 (m, 2H), 1.54 – 1.39 (m, 2H), 0.99
(t, J = 7.4 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 166.98, 157.47,
153.71, 145.35, 140.84, 137.22, 137.11, 134.29, 131.09, 128.98,
128.56, 128.25, 127.74, 122.44, 117.96, 64.80, 31.01, 19.43, 13.87; IR
(KBr) 2958, 2927, 2872, 1768, 1710 cm-1; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C19H17ClNO4S 390.0567; Found 390.0569.
(E)-Butyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)furan-3-
(E)-Butyl
3-(4-chloro-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)acrylate (Table 4, 5c). brownish gummy liquid. eluent, hexane/ethyl
acetate (93:7), (94 mg, 56%). 1H NMR (300 MHz, Chloroform-d) δ 8.58
(dt, J = 16.1, 0.7 Hz, 1H), 8.24 (ddd, J = 7.9, 1.6, 0.6 Hz, 1H), 7.84 (ddd,
J = 8.2, 7.3, 1.6 Hz, 1H), 7.73 (ddd, J = 8.1, 1.3, 0.6 Hz, 1H), 7.63 (dd,
J = 1.9, 0.7 Hz, 1H), 7.54 (ddd, J = 7.9, 7.3, 1.3 Hz, 1H), 6.82 (dd, J =
1.9, 0.6 Hz, 1H), 6.39 (d, J = 16.1 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 1.73
yl)phenyl)acrylate (Table 5, 6c). white solid ; mp 63-68 °C. eluent,
hexane/ethyl acetate (94:6), (124 mg, 68%).1H NMR (300 MHz,
Chloroform-d) δ 8.60 (dt, J = 15.8, 0.6 Hz, 1H), 8.26 (ddd, J = 7.9, 1.6,
0.6 Hz, 1H), 8.13 (d, J = 2.2 Hz, 1H), 7.85 (ddd, J = 8.1, 7.3, 1.6 Hz,
1H), 7.72 (ddd, J = 8.1, 1.3, 0.6 Hz, 1H), 7.67 – 7.47 (m, 3H), 6.35 (d, J
= 15.9 Hz, 1H), 4.23 (t, J = 6.6 Hz, 2H), 1.77 – 1.62 (m, 2H), 1.51 –
1.35 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
166.72, 158.98, 155.36, 146.24, 142.97, 136.91, 135.98, 134.49,
132.14, 131.02, 130.28, 129.79, 129.35, 128.75, 127.79, 121.29,
116.93, 64.72, 30.93, 19.37, 13.85; IR (KBr) 2958, 2926, 2851, 1766,
1716 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H19ClNO4
384.1003; Found 384.1005.
(dd, J = 8.5, 5.9 Hz, 2H), 1.56 – 1.44 (m, 2H), 1.03 – 0.96 (m, 3H).13
C
NMR (101 MHz, CDCl3) δ 166.58, 158.19, 150.13, 147.21, 146.69,
146.27, 136.90, 134.32, 128.96, 128.83, 128.12, 127.53, 122.90,
117.14, 110.58, 64.80, 30.93, 19.41, 13.91. IR (KBr) 2964, 2931, 2873,
1770, 1712 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H18NO5
340.1185; Found 340.1185.
(E)-Methyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)thiophen-3-
(E)-Methyl
3-(4-bromo-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)acrylate (Table 4, 5d). yellow solid ; mp 159-162 °C. eluent,
hexane/ethyl acetate (93:7), (103 mg, 66%). 1H NMR (300 MHz,
Chloroform-d) δ 8.89 (dt, J = 16.1, 0.7 Hz, 1H), 8.21 (ddd, J = 7.9, 1.6,
0.6 Hz, 1H), 7.81 (ddd, J = 8.1, 7.2, 1.6 Hz, 1H), 7.69 (ddd, J = 8.1, 1.3,
0.6 Hz, 1H), 7.56 – 7.44 (m, 2H), 7.41 (dd, J = 5.3, 0.6 Hz, 1H), 6.42 (d,
J = 16.1 Hz, 1H), 3.85 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 167.38,
158.51, 153.42, 146.76, 140.51, 137.68, 136.78, 132.04, 130.68,
128.81, 128.58, 127.59, 127.53, 121.61, 116.86, 51.96; IR (KBr) 3020,
2924, 2852, 1758, 1745 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C16H12NO2S 314.0487; Found 314.0488.
yl)phenyl)acrylate (Table 5, 6d). white solid ; mp ˃ 200 °C. eluent,
hexane/ethyl acetate (94:6), (119 mg, 62%). 1H NMR (300 MHz,
Chloroform-d) δ 8.59 (d, J = 15.9 Hz, 1H), 8.37 – 8.17 (m, 2H), 7.86 (d,
J = 1.3 Hz, 1H), 7.79 – 7.64 (m, 2H), 7.64 – 7.46 (m, 2H), 6.36 (d, J =
15.9 Hz, 1H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.05,
158.95, 155.22, 146.24, 143.51, 136.95, 135.11, 134.88, 133.17,
131.20, 129.93, 129.35, 128.74, 127.83, 123.99, 120.76, 116.92, 51.96;
IR (KBr) 3064, 2951, 1773, 1727, 1629 cm-1; HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C18H13BrNO4 386.0028; Found 386.0021.
(E)-Methyl
3-(2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)-4-
(E)-Methyl
3-(2-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-
(trifluoromethyl)phenyl)acrylate (Table 5, 6e). brownish solid; mp 90-
94 °C. eluent, hexane/ethyl acetate (94:6), (106 mg, 57%). 1H NMR
(500 MHz, Chloroform-d) δ 8.65 (d, J = 15.9 Hz, 1H), 8.41 (dd, J = 1.8,
0.9 Hz, 1H), 8.27 (dd, J = 7.8, 1.4 Hz, 1H), 7.89 – 7.84 (m, 1H), 7.83 –
7.76 (m, 2H), 7.73 (dd, J = 7.9, 1.1 Hz, 1H), 7.60 (td, J = 7.6, 1.2 Hz,
1H), 6.41 (d, J = 15.8 Hz, 1H), 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 166.83, 158.88, 155.32, 146.20, 143.39, 139.51, 137.03, 131.98 (q,
yl)thiophen-3-yl)acrylate (Table 4, 5e). yellow solid ; mp 172-177 °C.
eluent, hexane/ethyl acetate (93:7), (111 mg, 64%). 1H NMR (300 MHz,
Chloroform-d) δ 8.84 (d, J = 16.1 Hz, 1H), 8.16 (d, J = 2.4 Hz, 1H), 7.75
(dd, J = 8.7, 2.4 Hz, 1H), 7.64 (d, J = 8.6 Hz, 1H), 7.55 (dd, J = 5.2, 0.7
Hz, 1H), 7.41 (dd, J = 5.3, 0.5 Hz, 1H), 6.42 (d, J = 16.1 Hz, 1H), 3.85
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.34, 157.48, 153.53, 145.20,
140.81, 137.48, 137.11, 134.24, 131.50, 131.12, 129.02, 128.17,
127.71, 121.80, 117.83, 52.05; IR (KBr) 2960, 2954, 2850, 1767, 1718
4
2JC-F = 34.0 Hz), 130.35, 129.51, 129.31, 128.83, 128.56 (q, JC-F = 3.0
Hz), 127.87, 127.37 (q, 3JC-F = 4.0 Hz), 122.21, 121.96 (q, 1JC-F = 265.0
Hz), 116.98, 52.09.; IR (KBr) 2925, 2354, 1766, 1722, 1628 cm-1;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H13F3NO4 376.0797;
Found 376.0794.
cm-1; HRMS (ESI-TOF) m/z: [M
348.0097; Found 348.0097.
+
H]+ Calcd for C16H11ClNO4S
(E)-Butyl
3-(4-methyl-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-
yl)phenyl)acrylate (Table 5, 6a). brownish gummy liquid. eluent,
hexane/ethyl acetate (94:6), (125 mg, 69%).1H NMR (300 MHz,
Chloroform-d) δ 8.63 (d, J = 15.9 Hz, 1H), 8.25 (dd, J = 7.9, 1.6 Hz, 1H),
7.96 – 7.91 (m, 1H), 7.85 – 7.79 (m, 1H), 7.75 – 7.68 (m, 1H), 7.63 –
7.51 (m, 2H), 7.43 – 7.32 (m, 1H), 6.35 (d, J = 15.8 Hz, 1H), 4.27 –
4.18 (m, 2H), 2.45 (s, 3H), 1.75 – 1.58 (m, 2H), 1.42 (ddq, J = 16.7, 9.4,
7.3 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
167.09, 159.53, 156.68, 146.55, 143.94, 140.24, 136.77, 133.17,
132.92, 130.85, 129.62, 128.92, 128.61, 128.36, 127.65, 119.96,
Acknowledgements
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
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We are pleased to acknowledge the financial support from
Indian National Science Academy, New Delhi for the award of
INSA Senior Scientist position to B.C.R. S. P. thanks CSIR for
his fellowship.
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…
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10.1002/ejoc.201900935
European Journal of Organic Chemistry
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Palladium-catalyzed
olefination of 4H-
Key Topic*
C-H activation
Benzo[d][1, 3] oxazin-4-
one derivatives with
activated alkenes via
preferential cyclic imine-
N-directed aryl C-H
Olefination of benzoxazinones
Subir Panja, Srabani Maity,
Biju Majhi and Brindaban C.
Ranu*
activation
An efficient procedure for the Pd-catalyzed olefination of 4H-
benzo[d][1,3]oxazin-4-ones with activated alkenes has been
achieved via C-H activation.
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Author(s), Corresponding Author(s)*
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