Synthesis of α,β-Unsaturated N-Aryl Ketonitrones from Oximes and Diaryliodonium Salts: Observation of a Metal-Free N-Arylation Process

Article abstract of DOI:10.1021/acs.joc.5b01716

An efficient transition-metal-free method for the preparation of α,β-unsaturated N-aryl ketonitrones under mild conditions has been developed. This reaction shows good functional group tolerance for both electron-rich and electron-deficient substituents on both oximes and diaryliodonium salts. Two examples of gram-scale preparations have been realized in good yields. Further transformations of these nitrones to different N-heterocycles have been demonstrated. DFT calculations suggest that N-arylation products are formed by [1,3]-phenyl migration of an O-coordinated oximate complex via a four-centered transition state, while the O-arylation products are formed by [1,3]-phenyl migration of a N-coordinated oximate complex.

Full text of DOI:10.1021/acs.joc.5b01716

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Article
Synthesis of alpha,beta-Unsaturated N-Aryl Ketonitrones from Oximes and
Diaryliodonium Salts: Observation of A Metal Free N-Arylation Process
Xiao-Pan Ma, Wei-Min Shi, Xue-Ling Mo, Xiao-Hua Li, Liang-
Gui Li, Cheng-Xue Pan, Bo Chen, Gui-Fa Su, and Dong-Liang Mo
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 22 Sep 2015
Downloaded from http://pubs.acs.org on September 26, 2015
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Synthesis of α,β-Unsaturated N-Aryl Ketonitrones from Oximes and
Diaryliodonium Salts: Observation of A Metal Free N-Arylation
Process
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XiaoꢀPan Ma,a WeiꢀMin Shi,a XueꢀLing Mo,a XiaoꢀHua Li,a LiangꢀGui Li,a
ChengꢀXue Pan, a Bo Chen,*b GuiꢀFa Su*a and DongꢀLiang Mo*a
aKey Laboratory for the Chemistry and Molecular Engineering of Medicinal
Resources, Ministry of Education of China; School of Chemistry & Pharmaceutical
Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin 541004, China.
bDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY
14853, United State.
Eꢀmail: moeastlight@mailbox.gxnu.edu.cn; gfysglgx@163.com; cberic@hotmail.com
HO
Ar3
R1
O
N
N
KOH/CCl4
Ar3
I OTf
Ar4
+
R1
R2
Ph
R2
RT
Ph
I
Ph
Transition-metal free
Mild conditions
Gram scale
30 examples
up to 88 % yields
I
Ph
O
O
vs
R2
N
N
R1
O-arylation
R2
R1
N-arylation
ABSTRACT: An efficient transitionꢀmetal free method for the preparation of
α,βꢀunsaturated Nꢀaryl ketonitrones under mild conditions has been developed. This
reaction shows good functional group tolerance for both electronꢀrich and
electronꢀdeficient substituents on both oximes and diaryliodonium salts. Two
examples of gram scale preparations have been realized in good yields. Further
transformations of these nitrones to different Nꢀheterocycles have been demonstrated.
DFT calculations suggest that Nꢀarylation products are formed by [1,3]ꢀphenyl
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migration of an Oꢀcoordinated oximate complex via a fourꢀcentered transition state
while the Oꢀarylation products are formed by [1,3]ꢀphenyl migration of a
Nꢀcoordinated oximate complex.
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INTRODUCTION
Oximes, owing to their ability to act as ambident nucleophiles (Oꢀ or
Nꢀnucleophiles), have been extensively utilized as important starting materials to
construct key building blocks in organic synthesis.1,2 Arylation of the NꢀO bond is one
of the most important transformations of oximes. OꢀArylations have been used to
build aryloxyamines, which are important precursors of Oꢀaryloximes or benzofurans,
while Nꢀarylations have been employed to prepare oxyarylamines.3 In the past,
efficient Oꢀarylations of oximes have been achieved by transitionꢀmetal catalyzed
crossꢀcoupling reactions of oximes with aryl halides or aryl boronic acids.4,5 For
example, Maitra and Wailes reported the coupling of oximes with aryl iodides
catalyzed by a CuI/1,10ꢀphenanthroline catalyst system.4a In 2010, Buchwald
developed an efficient Pd catalyst for the Oꢀarylation of ethyl acetohydroximate with
aryl chlorides, bromides, and iodides to prepare Oꢀarylhydroxyamines and substituted
benzofurans (Scheme 1ꢀA).4b In addition, both Huang and Meyer have reported the
copperꢀmediated coupling of oximes with arylboronic acids to form Oꢀarylation
products (Scheme 1ꢀA).5 More recently, Anderson and coworkers found that
α,βꢀunsaturated Nꢀaryl ketonitrones can be generated by copperꢀmediated Nꢀarylation
of chalcone oximes with arylboronic acids in good yields (Scheme 1ꢀB).6 Despite the
efficiencies of these metal catalyzed or mediated arylations of oximes, these methods
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suffer from several drawbacks such as harsh conditions, prolonged reaction times, the
requirement of complex ligands, and traceꢀmetal impurities remaining in the products.
To overcome the aforementioned drawbacks, recent emphasis has been placed on
the development of metal free methods for Oꢀarylation or Nꢀarylation of oximes using
diaryliodonium salts as arylation reagents.7 Diaryliodonium salts are readily availabile
reagents that exhibit highꢀreactivity and selectivity, good tolerance of a wide range of
functional groups, and are considered to be nonꢀtoxic in many areas of organic
synthesis.8 Very recently, Kürti and Olofsson independently developed metalꢀfree
methods for the Oꢀarylation of oximes with diaryliodonium salts to access
Oꢀarylhydroxylamines for synthesis of benzofuran scaffolds (Scheme 1ꢀC).7b,c
In contrast to the work of Kürti and Olofsson, herein we report, a metalꢀfree
Nꢀarylation of oximes with diaryliodonium salts to produce α,βꢀunsaturated Nꢀaryl
ketonitrones (Scheme 1ꢀD). Due to their rich chemistry resulting from the inclusion of
the conjugated double bond moiety in nitrone, α,βꢀunsaturated Nꢀaryl ketonitrones
have recently gained much attention as key building blocks in the synthesis of highly
complex molecules.9 Traditional methods for the preparation of nitrones, such as the
condensation of a hydroxylamine with a carbonyl compound10 or oxidation of a
secondary hydroxylamine,11 are inefficient in making α,βꢀunsaturated Nꢀaryl
ketonitrones because of the low nucleophilicity of Nꢀaryl hydroxylamines and side
reactions such as oxidation of the double bond. The reported method in this article
represents an advance in synthesizing α,βꢀunsaturated Nꢀaryl ketonitrones.12
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A) Pd or Cu-catalyzed cross-coupling O-arylation of oximes
4
5
[Pd] or [Cu]
ArONH2
OH
O
Ar
ArX
N
N
R3
6
7
8
R1
R2
R1
R2
R1
[Cu]/O2
R1 = OEt, R2 = Me or
R1 = Aryl, R2 = Alkyl
O
ArB(OH)2
9
B) Cu-mediated cross-coupling N-arylation of oximes
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HO
N
Ar
O
N
Cu(OAc)2 (2.0 equiv.)
ArB(OH)2
+
Ar1
Ar2
Ar1
Ar2
Pyridine (10.0 equiv.),
DCE, in air
30-70% yields
C) Metal-free O-arylation of oximes
Ar3ONH2
R3
O
Ar3
OH
N
N
base
Ar3Ar4IOTf
+
R1
R2
R1
R2
R1
R1 = OEt, R2 = Me or
R1 = Aryl, R2 = Alkyl
O
D) This work : metal-free N-arylation of oximes
Ar3
R
O
HO
N
N
base
Ar3Ar4IOTf
+
R
Ar2
Ar2
R = aryl, vinyl, heterocycle
31-88% yields
Scheme 1 Arylation Strategies of Oximes
RESULTS and DISCUSSION
Our investigation began with the reaction of different types of oximes 1 with
diphenyliodonium triflate 2a. These transformations were carried out with potassium
tertꢀbutoxide in DMF at ambient temperature (Scheme 2). When ethyl
acetohydroximate and acetophenone oxime were combined under the reaction
conditions only Oꢀarylation products were isolated in good yields, and <5% yields of
Nꢀarylation products were observed in the crude reaction mixture. The isolated yields
of the Oꢀarylation products were in agreement with the literature.8b In contrast, when
cyclohexanone oxime was treated with diaryliodonium salt 2a, the reaction mixture
was complex and only <10% yield of the Oꢀarylation product was observed. To our
surprise, in the case of benzophenone oxime, chalcone oxime, and
dibenzylideneacetone oxime, a mixture of Oꢀ and Nꢀarylation products were observed.
For dibenzylideneacetone oxime, the Nꢀarylation product was isolated in 73% yield as
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the major product. Encouraged by the observed switch in selectivity from Oꢀarylation
to Nꢀarylation, we decided to optimize the reaction conditions of this Nꢀarylation
process.
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Ph
OH
O
Ph
O
N
N
N
t-BuOK/DMF
+
Ph2IOTf
+
R1
R2
R1
R2
R1
R2
rt
1
2a
O-product 4
N-product 3
OH
N
OH
OH
N
N
EtO
Me
Ph
Me
O
O
O
:<10%,
N: 0%
: 76%,
N: 0%
: 70%,
N: 0%
OH
OH
OH
N
N
N
Ph
Ph
Ph
Ph
Ph
Ph
O
O
N
: 67%,
N: 13%
: 55%,
: 34% (E/ Z = 8:1)
O
: 22%,
N: 73%
Scheme 2 Selective O-Arylation and NꢀArylation for Oximes
Dibenzylideneacetone oxime 1a was initially chosen as the model substrate for
screening conditions for oxime Nꢀarylation. As illustrated in Table 1, a screen of
various solvents showed that CCl4 was the best solvent for this transformation (entries
1ꢀ7). The choice of base had little effect on the yield of nitrone 3a, except for pyridine,
which prevented the desired transformation (entries 7, 9, 10 vs 11). The Nꢀarylation
reaction proceeded smoothly and provided analogous yields either in the presence or
absence of water (entry 8). No desired product was observed and only oxime 1a was
recovered in the absence of base (entry 12).
Table 1. Optimization of Reaction. a
OH
Ph
O
N
N
base/solvent
rt
+
Ph2IOTf
Ph
Ph
Ph
Ph
1a
2a
3a
Entry
Base
Solvent
Time
3a,
(h)
Yield %b
69
1
KOH
DMF
13
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2
KOH
KOH
KOH
KOH
KOH
KOH
KOH
tꢀBuOK
Cs2CO3
Pyridine
ꢀ
DMSO
MeCN
THF
13
1.5
0.5
1.6
2.5
2.5
5
45c
60
67
70
64
75d
74e
74
71
0
3
4
5
PhMe
DCE
CCl4
6
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7
8
CCl4
9
CCl4
4
10
11
12
CCl4
7.5
24
24
CCl4
CCl4
0
a
Reaction conditions: oxime 1a (0.5 mmol), Ph2IOTf (1.5 equiv.), KOH (1.5 equiv.),
CCl4 (5 mL), rt. b Isolated yields. c Oꢀarylation product 4a was also isolated with 40%
yield. d Oꢀarylation product 4a was also isolated with 10% yield. H2O (0.5 mL) was
e
added in CCl4.
To examine the scope of the Nꢀarylation of oximes with diaryliodonium reagents,
the most general conditions identified in Table 1 (entry 7) were applied to various
substrates. As shown in Table 2, oximes with both electronꢀrich and electronꢀdeficient
styrenyl functional groups with orthoꢀ, metaꢀ, paraꢀsubstitution patterns, were
tolerated under the reaction conditions and provided the desired nitrones in moderate
to good yields (Table 2, entries 1ꢀ8). However, when oxime 1e was tested, the yield of
Nꢀarylation decreased sharply in either toluene or THF perhaps due to the poor
solubility of the substrate (Table 2, entry 5). Interestingly, the unsymmetrically
substituted oximes 1i -1n (E/Z = 1:1) were also smoothly converted to 1:1 mixtures of
E/Z isomers of nitrones 3 (Table 2, entries 9ꢀ14). When oxime 1i was used as
substrate, product 3i was obtained in 78% yield in THF while only 46% yield in CCl4
(Table 2, entries 9). To our delight, the reaction tolerated heterocylic substitutents
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such as 2ꢀfuranyl and 2ꢀthienyl groups and good yields of the corresponding nitrones
were achieved (Table 2, entries 7 and 8). When an oxime containing two conjugated
double bonds was used as substrate, the desired nitrone 3n was obtained with 67%
yield (Table 2, entry 14). The conjugated system in 3n further enhances the potential
synthetic applications of the nitrone products.
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Table 2. The Scope of Oximes.a
HO
N
Ph
O
N
KOH/CCl4
Ar1
Ar2
+
Ph2IOTf
Ar1
Ar2
1
2a
3
Entry
1
Ar1
Ph
Ar2
Yield %b
75
65 (39c,56d)
81 (41d)
76 (61d)
46 (52c,50d)
68
1
3
Ph
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
2
4ꢀMeO(C6H4)
4ꢀMe(C6H4)
4ꢀCF3(C6H4)
3ꢀBr(C6H4)
2ꢀBr(C6H4)
2ꢀ(Furanyl)
2ꢀ(Thienyl)
Ph
4ꢀMeO(C6H4)
4ꢀMe(C6H4)
4ꢀCF3(C6H4)
3ꢀBr(C6H4)
2ꢀBr(C6H4)
2ꢀ(Furanyl)
2ꢀ(Thienyl)
4ꢀMeO(C6H4)
4ꢀCF3(C6H4)
4ꢀBr(C6H4)
3ꢀBr(C6H4)
2ꢀBr(C6H4)
PhCH=CH
3
4
5
6
7
74
1g
1h
1i
3g
3h
3i
8
75
9
46,78d (1:1)e
75 (1:1)e
75 (1:1)e
77 (1:1)e
60 (1:1)e
67 (1:1)e
10
11
12
13
14
Ph
1j
3j
Ph
1k
1l
3k
3l
Ph
Ph
1m
1n
3m
3n
Ph
a
Reaction conditions: oxime 1 (0.5 mmol), Ph2IOTf (1.5 equiv.), KOH (1.5 equiv.),
CCl4 (5 mL), rt, 0.5ꢀ24 h. b Isolated yields. c Run in toluene. d Run in THF. e The C=N
geometry ratio of E:Z in nitrones.
In addition to screening oxime substrates, a variety of diaryliodonium salts 2 were
tested to examine its effect on the formation of Nꢀaryl nitrones. These reagents were
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easily prepared in one step from commercially available starting materials such as aryl
boronic acids.13 As shown in the Table 3, both electronꢀrich and electronꢀdeficient
diaryliodonium salts 2, with paraꢀ, metaꢀ or orthoꢀsubstituents provided the
corresponding nitrones in good yields. It is worth noting that iodonium reagents with
orthoꢀmethyl or orthoꢀbromo, and heterocyclic substituents also gave the desired
nitrones (Table 3, entries 9, 14 and 15). Analogous challenging nitrones were obtained
with lower yields by Yang’s method,12 and were not discussed in the copperꢀmediated
crossꢀcoupling reaction of oximes with arylboronic acids developed by Anderson and
coworkers in 2013.6 To our delight, when unsymmetrical diaryliodonium salts were
tested, the Nꢀarylation reaction proceeded with high chemoselectivity and
electronꢀdeficient aryl moieties were preferentially transferred to the nitrones (Table 3,
entries 10ꢀ14).14 The bromo, chloro, thienyl, nitro, and ester functional groups were
all tolerated as substituents of the iodonium reagents in this transformation.
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Table 3. The Scope of diaryliodionium salts a
Ar3
O
HO
N
N
KOH/CCl4
Ar3
I
OTf
+
Ph
Ph
Ar4
Ph
Ph
3ab-3ao
1a
2
Entry
Ar3
Ph
Ar4
Ph
Yield %b
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
3
1
2
3
4
5
6
7
8
9
75
74
71
78
71
73
65
70
3a
4ꢀMeO(C6H4)
4ꢀMe(C6H4)
ꢀBu(C6H4)
4ꢀCl(C6H4)
4ꢀF(C6H4)
3ꢀNO2(C6H4)
3,5ꢀMe2(C6H4)
2ꢀMe(C6H4)
Ph
4ꢀMeO(C6H4)
4ꢀMe(C6H4)
ꢀBu(C6H4)
4ꢀCl(C6H4)
4ꢀF(C6H4)
3ꢀNO2(C6H4)
3,5ꢀMe2(C6H4)
2ꢀMe(C6H4)
4ꢀMeO(C6H4)
4ꢀMeO(C6H4)
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3a
4ꢀ
t
4ꢀ
t
65
69
58
10
11
2aa
2j
4ꢀCF3(C6H4)
3aj
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4ꢀBr(C6H4)
3ꢀBr(C6H4)
2ꢀBr(C6H4)
4ꢀMeO(C6H4)
4ꢀMeO(C6H4)
4ꢀMeO(C6H4)
4ꢀMeO(C6H4)
Ph
68
72
88
44c
81
2k
2l
2m
2n
2o
3ak
3al
3am
3an
3ao
3ꢀ(thienyl)
4ꢀCO2Me(C6H4)
Reaction conditions: oxime 1a (0.5 mmol), Ar3Ar4IOTf (1.5 equiv.), KOH (1.5
a
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equiv.), CCl4 (5 mL), rt, 0.5ꢀ24 h. b Isolated yields. c 3ab was also obtained with 40%
yield.
When chalcone oximes (1o-1r) were subjected to the optimal oxime Nꢀarylation
conditions described above, the desired products were obtained in moderate yields
with the Eꢀisomers as the major products (Scheme 3).12 Interestingly, the
E/Zꢀgeometry ratio of the C=N bond in nitrones 3 ranged from 8:1 to 12:1 (3o-3r). To
our delight, the sterically hindered orthoꢀsubstituted Nꢀaryl nitrone 3r was obtained in
31% yield.12
OH
N
Ar
O
KOH/CCl4
RT
N
Ar2IOTf
+
Ar1
Ar2
Ar1
Ar2
3o-3r
2
1o-1r
Me
MeO
Ph
O
Ph
Ph
O
N
N
O
O
N
N
Ph
Ph
(65%, E:Z =10:1)
Ph
Ph
Ph
Ph
OMe
3p
(42%, E:Z = 12:1)
3o
3q (53%, E:Z = 8:1) 3r (31%, E:Z = 8:1)
Scheme 3. Synthesis of NꢀAryl Nitrones from Chalcone Oximes 1o-1r.
When radical trap TEMPO (2.0 equiv.) was added into the reaction of oxime 1a
and iodonium salt 2a, nitrone 3a was still obtained in 78% yield for 24h (Scheme 4ꢀ1),
which suggests that a radical mechanism is unlikely. The synthesis of nitrones by the
Nꢀarylation of oximes with diaryliodonium salts could occur via a direct CꢀN bond
forming pathway or an initial CꢀO bond forming step followed by a rearrangement.
When Oꢀarylation product 4a was subjected to the optimal Nꢀarylation reaction
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conditions for 72 h, nitrone 3a was not observed and only starting material was
recovered (Scheme 4ꢀ2). This experiment revealed that nitrone 3a cannot be formed
from a rearrangement of Oꢀarylation product 4a. However, when nitrone 3a was
subjected to the optimal condition, Oꢀarylation product was observed in 10% yield for
72 h (Scheme 4ꢀ3).15 This experiment suggests that the Oꢀarylation product might be
the thermodynamic product while nitrone was the kinetic product.
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1)
OH
N
O
Ph
O
N
N
+
Ph2IOTf
Ph
Ph
Ph
Ph
Ph
KOH/CCl4
RT, 24 h
1a
2a
3a
, 78% yield
Ph
O
KOH/CCl4
O
N
N
2)
3)
Ph
Ph
RT, 0-72 h
Ph
Ph
No Reaction
3a (0% yield)
4a
Ph
Ph
O
O
N
CCl4
N
RT, 72 h
Ph
Ph
Ph
4a no KOH, 0% yield
with KOH, 10% yield
Ph
3a
Scheme 4. The Mechanism Studies.
To further study the oxime Nꢀarylation reaction mechanism, DFT calculations
were carried out on a model system of divinyl oxime with diphenyliodonium triflate
(Scheme 5).16 It is proposed that this reaction begins with the deprotonation of oxime
by KOH;2a The resultant oximate anion, as an ambident nucleophiles, could attack
diphenyliodonium triflate as either the Oꢀnucleophile or the Nꢀnucleophile, leading to
the two distinct intermediates IM1 and IM2, respectively. IM1 is calculated to be
lower in energy than IM2 by 3.8 kcal/mol. We surmise that this difference, may be
due to the fact that the IM2 can be represented by a nonꢀchargeꢀseparated Lewis
structure while the IM1 cannot. We also explored theoretically the possibility of
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another resonance structure of oximate anion (nitroso carbanion) as a potential
Cꢀnucleophile to attack diphenyliodonium triflate. However, no intermediate structure
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with a CꢀI bond was located in our calculations.
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Ph
Ph
I
HO
R
O
R
N
N
KOH
OTf
R
R
-
OTf
R = vinyl
C-attack
N-attack
O-attack
Ph
Ph
Ph
N
Ph
O
N
Ph
I
IM2
I
IM3
IM1
I
Ph
O
R
O
5.1
(3.8)
0.0
R
N
R
(0.0)
R
not found
R
R
reductive
elimination
[1,3] phenyl
migration
reductive
elimination
[1,3] phenyl
migration
Ph
I
Ph
I
Ph
Ph
Ph
Ph
I
I
Ph
O
R
O
N
Ph
O
R
N
O
N
N
R
R
R
R
R
R
TS1 19.9
TS2 11.3
TS3 28.9
TS4 14.1
(20.8)
(12.9)
(28.2)
(15.2)
O
O
Ph
Ph
N
N
+ PhI
+ PhI
R
O-arylation product
R
R
R
N-arylation product
-60.9
-67.8
(-60.8)
(-66.4)
Scheme 5. Possible reaction pathways (R = vinyl), with calculated energies for
intermediates, transition states and products. Free energies in both gas phase (ꢀGgas)
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and in solvent (ꢀGsol in parenthesis) are given in units of kcal/mol. The most
favorable pathway that gives Nꢀarylation product is highlighted in red.
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Starting from either IM1 or IM2, there are two potential arylation pathways: 1)
direct reductive elimination at iodine center via a threeꢀmembered ring transition state
(TS1 and TS3), and 2) a [1,3]ꢀphenyl migration via a fourꢀmembered ring transition
state (TS2 and TS4). TS1 and TS4 lead to the Oꢀarylation product, while TS2 and
TS3 lead to Nꢀarylation product. Calculations show that TS2 is 15.3 kcal/mol lower
than TS3, 2.3 kcal/mol lower than TS4, and represents the lowest overall activation
barrier. These transition state energy differences suggest that the most favorable
pathway is the initial formation of Oꢀcoordinated diphenyliodonium oximate complex
IM1 followed by [1,3]ꢀphenyl migration, as highlighted in Scheme 5.17 This predicted
pathway gives Nꢀarylation product, in agreement with experiments. DFT calculations
also show that the most favorable Oꢀarylation pathway is the formation of
Nꢀcoordinated diphenyliodonium oximate complex IM2 followed by [1,3]ꢀphenyl
migration via TS4.18 The Oꢀarylation product is computed to be 5.6 kcal/mol lower in
energy than the Nꢀarylation product, in agreement with the experiments that the
Oꢀarylation product is the thermodynamic product and the Nꢀarylation product is the
kinetic product (Scheme 4ꢀ2 and 4ꢀ3).
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In order to show the superiority of this new transformation, gramꢀscale reactions
were performed using the optimal condition for oxime Nꢀarylation. When 2.2 g (8.8
mmol) of oxime 1a were treated with 2a for 2.5 h, 2.1 g of the desired nitrone 3a was
obtained in 73% yield (Scheme 6ꢀ1). Treatment of oxime 1o (2.2 g, 10 mmol) with 2a,
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gave nitrones 3o in 60% yield (Scheme 6ꢀ2).
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With Nꢀaryl nitrones in hand, we studied their synthetic applications (Scheme 6ꢀ3).
When nitrone 3a was heated at 100 ˚C for 18 h, the quinoline product 5 was afforded
in 56% yield. When nitrone 3a was treated with pꢀtolisocyanate, Nꢀvinyl amidine 6
was isolated in excellent yield. When 3a was treated with monoꢀsubstituted allenoate,
dihydrocarbazole 7 was isolated with 64% yield. These quinoline, amidine and
dihydrocarbazole products are important and useful intermediates in organic
synthesis.18 The facile method that we have developed for the synthesis of Nꢀaryl
nitrones will allow these important scaffolds to be studied more frequently.
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1a
1) Gram Scale for oxime
Ph
O
OH
N
N
KOH/CCl4
2.5 h
Ph2IOTf
+
Ph
Ph
Ph
Ph
1a (2.2 g, 8.8 mmol)
3a, 2.1 g, 73% yield
2a
2) Gram Scale for oxime 1o
OH
N
Ph
Ph
O
N
KOH/CCl4
1.5 h
+
Ph2IOTf
Ph
Ph
(2.2 g, 10 mmol)
Ph
1o
2a
3o, 1.8 g, 60% yield
3) Applications of Nitrones
Ph
Ph
O
N
lot-p
lot-p
N
N=C=O
toluene
100 °C
toluene
Ph
Ph
Ph
Ph
N
N
Ph
3a
Ph
5, 56% yield
6, 96% yield
CO2n-Bu
SiO2, toluene
Ph
Ph
CO2n-Bu
7, 64% yield
N
H
Scheme 6. Gram Scales and Synthetic Applications of Nitrone 3a.
CONCLUSIONS
In summary, we have shown that the α,βꢀunsaturated Nꢀaryl ketonitrones can be
prepared in oneꢀstep from the corresponding oximes through a metalꢀfree Nꢀarylation
reaction with diaryliodonium salts under mild conditions. The reaction tolerates
electronꢀrich or electronꢀdeficient substituents on both the oximes and the
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diaryliodonium reagents. In particular, Nꢀorthoꢀsubstituted aryl ketonitrones and
Nꢀheterocycleꢀsubstituted nitrones are easily obtained by this method. The salient
features of this transformation, includes simple conditions, short reaction times, good
yields, high selectivity for diaryliodonium salts, the ability to scaleꢀup to gram scale,
and the ability to facilitate further investigation of nitrone chemistry. Applications of
the Nꢀarylated nitrones products to the synthesis of different Nꢀheterocycles have also
been demonstrated. DFT calculations suggest that Nꢀaryl nitrones are formed via a
four membered ring transition state after the formation of Oꢀcoordinated
diaryliodonium oximate.
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EXPERIMENTAL SECTION
General Methods. All reactions were performed under an atmosphere of air.
Commercially available reagents were used without further purification. The NMR
spectra were recorded in CDCl3 or DMSOꢀd6 on 400 MHz, 500MHz, or 600MHz
instrument with TMS as the internal standard. NMR data are represented as follows:
chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet), coupling constants in hertz (Hz), and integration. IR spectra were recorded
on FTꢀIR spectrometer, and only major peaks are reported in cm‒1. HRMS were
measured in EI or ESI mode and the mass analyzer of the HRMS was TOF. Flash
column chromatography was performed on silica gel (300ꢀ400 mesh). The oximes 1a,
1i, 1j, 1o and 1p,6,20 1b,21 1c,22 1g and 1h,23 diaryliodonium salts 2a, 2aa, 2c and
2o,13a, 24 2b, 2d, 2e, 2f and 2i,25 2g,26 2h,27 2j,28 2k,29 and 2l30 were prepared according
to literature methods and their spectral data matched literature values.
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N-Arylation of Oximes to Prepare Nitrones 3：A round bottle flask, open to the air,
was charged with oxime 1 (0.5 mmol), CCl4 (5 mL) and KOH (0.75 mmol, 1.5 equiv.).
The mixture was stirred vigorously at RT for 5 min. Then diaryliodonium salt 2 (0.75
mmol, 1.5 equiv.) was added in one portion. The reaction was monitored by TLC until
the oxime was consumed completely. At this time, the CCl4 was removed under
reduced pressure and crude product was purified by flash chromatography (the crude
residue was dryꢀloaded on silica gel; 1:10ꢀ1:1 ethyl acetate:petroleum ether) to
provide nitrones 3 as solid.
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N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3a), 0.122 g, 75%
1
yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.65ꢀ7.61 (m, 3H), 7.59 (d, J =
17.5 Hz, 1H), 7.51ꢀ7.45 (m, 5H), 7.41 (t, J = 7.5 Hz, 2H), 7.36 (d, J = 7.0 Hz, 1H),
7.32ꢀ7.28 (m, 5H), 7.00 (d, J = 16.0 Hz, 1H), 6.67 (d, J = 16.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ 146.5, 139.6, 136.5, 136.1, 134.8, 129.6, 129.3, 129.2, 129.1,
128.9, 128.8, 128.7, 127.4, 126.8, 124.7, 120.5, 119.5; IR (thin film) 3055, 1593,
1487, 1229, 965, 769, 690 cm‒1; HRMS (ESI) m/z calcd. for C23H20NO (M+H)+
326.1545, found 326.1542; m.p: 163ꢀ164 °C.
N-((1E,4E)-1,5-Bis(4-methoxyphenyl)penta-1,4-dien-3-ylidene)aniline oxide (3b)，
0.125 g, 65% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.57 (d, J = 8.5 Hz,
2H), 7.51ꢀ7.49 (m, 4H), 7.46ꢀ7.42 (m, 3H), 7.23 (d, J = 8.5 Hz, 2H), 6.94ꢀ6.91 (m,
3H), 6.84 (d, J = 8.5 Hz, 2H), 6.50 (d, J = 16.5 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H); 13C
NMR (125 MHz, CDCl3): δ 160.5, 160.2, 147.2, 146.4, 139.4, 134.7, 129.4, 129.3,
129.1, 128.9, 128.8, 128.2, 124.7, 118.5, 117.5, 114.3, 114.2, 55.4, 55.3; IR (thin film)
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3034, 2836, 1598, 1509, 1252, 962, 821, 769, 692 cm‒1; HRMS (ESI) m/z calcd. for
C25H24NO3 (M+H)+ 386.1756, found 386.1752; m.p: 150ꢀ152 °C.
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N-((1E,4E)-1,5-Dip-tolylpenta-1,4-dien-3-ylidene)aniline oxide (3c), 0.143 g, 81%
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1
yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.61 (d, J = 16.5 Hz, 1H),
7.55ꢀ7.49 (m, 5H), 7.46ꢀ7.42 (m, 3H), 7.20ꢀ7.16 (m, 4H), 7.11 (d, J = 8.0 Hz, 2H),
6.96 (d, J = 16.5 Hz, 1H), 6.60 (d, J = 16.5 Hz, 1H), 2.37 (s, 3H), 2.32 (s, 3H); 13C
NMR (125 MHz, CDCl3): δ 146.8, 146.6, 139.6, 139.4, 139.0, 134.9, 133.8, 133.4,
129.6, 129.5, 129.4, 129.2, 127.5, 126.8, 124.8, 119.7, 118.6, 21.4, 21.3; IR (thin film)
3019, 2860, 1599, 1509, 1229, 964, 774, 696 cm‒1; HRMS (ESI) m/z calcd. for
C25H24NO (M+H)+ 354.1858, found 354.1856; m.p: 146ꢀ147 °C.
N-((1E,4E)-1,5-Bis(4-(trifluoromethyl)phenyl)penta-1,4-dien-3-ylidene)aniline
oxide (3d), 0.176 g, 76% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.72 (d,
J = 8.0 Hz, 2H), 7.66ꢀ7.65 (m, 4H), 7.57 (d, J = 8.0 Hz, 2H), 7.50 (s, 5H), 7.39 (d, J =
8.0 Hz, 2H), 7.01 (d, J = 16.5 Hz, 1H), 6.77 (d, J = 16.5 Hz, 1H); 13C NMR (125
MHz, CDCl3): δ 146.3, 145.4, 139.8, 139.3, 137.6, 132.6, 130.6 (q, J = 31.8 Hz),
130.1, 129.3, 127.5, 126.9, 125.8 (q, J = 3.6 Hz), 125.0 (q, J = 274 Hz), 124.9, 124.6,
122.9, 122.7, 121.3; IR (thin film) 3051, 1612, 1486, 1279, 981, 776, 695 cm‒1;
HRMS (ESI) m/z calcd. for C25H18F6NO (M+H)+ 462.1293, found 462.1268; m.p:
148ꢀ149 °C.
N-((1E,4E)-1,5-Bis(3-bromophenyl)penta-1,4-dien-3-ylidene)aniline oxide (3e),
1
0.110 g, 46% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.75 (s, 1H),
7.57ꢀ7.53 (m, 3H), 7.50ꢀ7.46 (m, 5H), 7.41ꢀ7.39 (m, 2H), 7.29ꢀ7.25 (m, 2H),
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7.20ꢀ7.17 (m, 2H), 6.89 (d, J = 16.0 Hz, 1H), 6.65 (d, J = 16.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ 146.4, 145.5, 138.6, 138.1, 137.7, 132.9, 131.9, 131.7, 130.4,
130.3, 130.2, 130.0, 129.8, 129.3, 125.9, 125.2, 124.6, 123.1, 123.0, 121.8, 120.6; IR
(thin film) 3054, 1588, 1463, 1229, 960, 773, 690 cm‒1; HRMS (ESI) m/z calcd. for
C23H18Br2NO (M+H)+ 481.9755, found 481.9761; m.p: 51ꢀ52 °C.
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N-((1E,4E)-1,5-Bis(2-bromophenyl)penta-1,4-dien-3-ylidene)aniline oxide (3f),
0.164 g, 68% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.97 (d, J = 16.5 Hz,
1H), 7.90 (d, J = 7.5 Hz, 1H), 7.65 (d, J = 16.5 Hz, 1H), 7.60ꢀ7.42 (m, 8H), 7.38 (d, J
= 7.5 Hz, 1H), 7.25ꢀ7.17 (m, 3H), 7.13 (t, J = 7.0 Hz, 1H), 6.64 (d, J = 16.5 Hz, 1H);
13C NMR (125 MHz, CDCl3): δ 146.4, 146.2, 137.8, 136.3, 136.0, 133.4, 133.2, 133.1,
130.1, 129.8, 129.7, 129.2, 127.6, 127.5, 127.4, 126.5, 124.9, 124.8, 124.7, 122.7,
121.8; IR (thin film) 3055, 1587, 1459, 1229, 958, 752, 692 cm‒1; HRMS (ESI) m/z
calcd. for C23H18Br2NO (M+H)+ 481.9755, found 481.9761; m.p: 118ꢀ119 °C.
N-((1E,4E)-1,5-Di(furan-2-yl)penta-1,4-dien-3-ylidene)aniline oxide (3g), 0.113 g,
1
74% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.84 (d, J = 15.5 Hz, 1H),
7.50ꢀ7.46 (m, 6H), 7.32ꢀ7.29 (m, 2H), 6.76 (d, J = 16.0 Hz, 1H), 6.58ꢀ6.55 (m, 2H),
6.47 (s, 1H), 6.38 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 152.8, 152.2, 146.6, 144.9,
143.9, 143.3, 129.5, 129.2, 126.1, 124.6, 120.4, 119.1, 116.3, 112.4, 112.2, 112.0,
111.3; IR (thin film) 3080, 1606, 1552, 1222, 964, 739, 691 cm‒1; HRMS (ESI) m/z
calcd. for C19H16NO3 (M+H)+ 306.1130, found 306.1127; m.p: 144ꢀ145 °C.
N-((1E,4E)-1,5-Di(thiophen-2-yl)penta-1,4-dien-3-ylidene)aniline oxide (3h),
0.126 g, 75% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.89 (d, J = 16.5 Hz,
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1H), 7.47ꢀ7.42 (m, 5H), 7.35ꢀ7.32 (m, 2H), 7.22ꢀ7.21 (m,2H), 7.09 (d, J = 16.5 Hz,
1H), 7.04 (s, 2H), 6.98 (t, J = 4.0 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H); 13C NMR (125
MHz, CDCl3): δ 146.2, 145.4, 142.1, 141.4, 132.3, 129.6, 129.2, 129.1, 128.8, 128.0,
127.9, 127.1, 126.3, 124.6, 124.5, 119.8, 118.1; IR (thin film) 3069, 1589, 1486, 1242,
957, 769, 691 cm‒1; HRMS (ESI) m/z calcd. for C19H16NOS2 (M+H)+ 338.0673,
found 338.0671; m.p: 140ꢀ141 °C
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N-((1E,4E)-1-(4-Methoxyphenyl)-5-phenylpenta-1,4-dien-3-ylidene)aniline oxide
1
(3i), 0.087 g, 46% yield (E/Z = 1:1), yellow solid. isomer 1: H NMR (500 MHz,
CDCl3): δ 7.65 (d, J = 16.5 Hz, 1H), 7.53ꢀ7.49 (m, 5H), 7.47ꢀ7.44 (m, 4H), 7.41 (t, J
= 7.5 Hz, 1H), 7.30ꢀ7.28 (m, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H),
6.64 (d, J = 16.5 Hz, 1H), 3.84 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 160.6, 146.9,
146.5, 139.5, 136.1, 135.0, 129.5, 129.2, 129.1, 129.0, 128.9, 128.8, 128.3, 127.5,
126.9, 124.8, 114.3, 55.3; isomer 2: 1H NMR (500 MHz, CDCl3): δ 7.61 (d, J = 16.5
Hz, 1H), 7.53ꢀ7.49 (m, 5H), 7.47ꢀ7.44 (m, 4H), 7.35 (t, J = 7.5 Hz, 1H), 7.30ꢀ7.28
(m, 2H), 7.23 (d, J = 8.5 Hz, 2H), 6.96 (d, J = 8.5 Hz, 2H), 6.52 (d, J = 16.0 Hz, 1H),
3.79 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 160.4, 147.0, 146.5, 139.7, 136.6, 134.7,
129.5, 129.2, 129.1, 129.0, 128.9, 128.8, 120.7, 119.7, 118.4, 117.4, 114.4, 55.4; IR
(thin film) 3030, 2850, 1599, 1508, 1251, 964, 753, 692 cm‒1; HRMS (ESI) m/z calcd.
for C24H22NO2 (M+H)+ 356.1651, found 356.1649; m.p: 54ꢀ55 °C.
N-((1E,4E)-1-Phenyl-5-(4-(trifluoromethyl)phenyl)penta-1,4-dien-3-ylidene)anili
1
ne oxide (3j), 0.147 g, 75% yield (E/Z = 1:1), yellow solid. isomer 1: H NMR (500
MHz, CDCl3): δ 7.74 (d, J = 8.5 Hz, 2H), 7.68ꢀ7.62 (m, 4H), 7.58 (d, J = 8.0 Hz, 1H),
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7.52ꢀ7.49 (m, 4H), 7.44 (t, J = 7.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.35ꢀ7.32 (m,
2H), 7.01 (d, J = 15.5 Hz, 1H), 6.71 (d, J = 16.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 146.4, 139.6, 137.5, 134.7, 132.6, 130.7 (q, J = 31.5 Hz), 129.8, 129.3,
128.9, 127.5, 126.8, 125.8 (q, J = 3.6 Hz), 125.1 (d, J = 271.1 Hz), 124.6, 122.8,
121.7, 120.3, 119.1; isomer 2: 1H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.5 Hz, 2H),
7.68ꢀ7.62 (m, 4H), 7.58 (d, J = 8.0 Hz, 1H), 7.52ꢀ7.49 (m, 4H), 7.44 (t, J = 7.0 Hz,
1H), 7.40 (d, J = 8.0 Hz, 2H), 7.35ꢀ7.32 (m, 2H), 7.04 (d, J = 15.5 Hz, 1H), 6.78 (d, J
= 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 145.8, 140.0, 136.4, 135.9, 132.6,
130.7 (q, J = 31.5 Hz), 129.9, 129.2, 128.8, 127.4, 126.9, 125.8 (q, J = 3.6 Hz), 124.9
(d, J = 271.1 Hz), 124.6, 122.9, 121.7, 120.3, 119.1; IR (thin film) 3057, 1613, 1461,
1277, 965, 752, 692 cm‒1; HRMS (ESI) m/z calcd. for C24H19F3NO (M+H)+ 394.1419,
found 394.1419; m.p: 55ꢀ57 °C
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N-((1E,4E)-1-(4-Bromophenyl)-5-phenylpenta-1,4-dien-3-ylidene)aniline
oxide
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(3k), 0.151 g, 75% yield (E/Z = 1:1), yellow solid. isomer 1: H NMR (500 MHz,
CDCl3): δ 7.62 (d, J = 7.0 Hz, 1H), 7.58ꢀ7.56 (m, 2H), 7.52ꢀ7.46 (m, 6H), 7.42ꢀ7.38
(m, 2H), 7.30ꢀ7.28 (m, 3H), 7.14 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 16.0 Hz, 1H), 6.66
(d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.4, 139.5, 138.0, 135.9,
135.0, 131.9, 129.7, 129.2, 128.9, 128.8, 128.1, 127.4, 126.8, 124.6, 121.2, 120.4,
1
120.0; isomer 2: H NMR (500 MHz, CDCl3): δ 7.62 (d, J = 7.0 Hz, 1H), 7.58ꢀ7.56
(m, 2H), 7.52ꢀ7.46 (m, 6H), 7.42ꢀ7.38 (m, 2H), 7.30ꢀ7.28 (m, 3H), 7.14 (d, J = 8.5 Hz,
2H), 6.92 (d, J = 16.5 Hz, 1H), 6.65 (d, J = 16.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 146.0, 139.5, 136.4, 135.5, 134.7, 133.1, 132.0, 129.2, 128.9, 128.8, 128.1,
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127.4, 126.8, 123.1, 122.7, 121.4, 119.2; IR (thin film) 3055, 1589, 1484, 1228, 962,
811, 769, 689 cm‒1; HRMS (ESI) m/z calcd. for C23H19BrNO (M+H)+ 404.0650,
found 404.0648; m.p: 144ꢀ146 °C.
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N-((1E,4E)-1-(3-Bromophenyl)-5-phenylpenta-1,4-dien-3-ylidene)aniline
oxide
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(3l), 0.155 g, 77% yield (E/Z = 1:1), yellow solid. isomer 1: H NMR (500 MHz,
CDCl3): δ 7.75 (s, 1H), 7.62 (d, J = 7.5 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.49ꢀ7.45
(m, 5H), 7.40 (d, J = 7.5 Hz, 2H), 7.32ꢀ7.26 (m, 3H), 7.20 (d, J = 7.5 Hz, 1H), 6.97 (d,
J = 16.0 Hz, 1H), 6.67 (d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.4,
139.6, 137.7, 135.9, 134.6, 132.9, 131.8, 130.3, 130.2, 129.7, 129.2, 128.9, 128.8,
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127.4, 126.8, 124.6, 121.9, 120.7, 119.3; isomer 2: H NMR (500 MHz, CDCl3): δ
7.58 (d, J = 7.0 Hz, 2H), 7.49ꢀ7.45 (m, 5H), 7.41 (s, 1H), 7.36 (d, J = 7.0 Hz, 2H),
7.32ꢀ7.26 (m, 3H), 7.18 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 16.0 Hz, 1H), 6.66 (d, J =
16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.0, 138.7, 138.2, 136.4, 134.6,
132.9, 131.9, 130.3, 130.2, 129.8, 129.3, 128.9, 128.8, 125.9, 125.2, 123.0, 122.9,
120.7, 120.4; IR (thin film) 3052, 1587, 1462, 1229, 963, 778, 691 cm‒1; HRMS (ESI)
m/z calcd. for C23H19BrNO (M+H)+ 404.0650, found 404.0648; m.p: 147ꢀ149 °C.
N-((1E,4E)-1-(2-Bromophenyl)-5-phenylpenta-1,4-dien-3-ylidene)aniline
oxide
1
(3m), 0.121 g, 60% yield (E/Z = 1:1), yellow solid. isomer 1: H NMR (500 MHz,
CDCl3): δ 7.88 (d, J = 16.0 Hz, 1H), 7.68ꢀ7.55 (m, 3H), 7.52ꢀ7.47 (m, 6H), 7.43ꢀ7.32
(m, 3H), 7.30ꢀ7.28 (m, 2H), 7.23ꢀ7.17 (m, 2H), 6.70 (d, J = 16.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ 146.7, 146.5, 139.9, 138.1, 136.5, 136.2, 135.3, 133.2, 129.8,
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129.3, 128.9, 127.8, 127.7, 127.6, 127.5, 126.9, 124.8, 123.0, 120.1; isomer 2: H
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NMR (500 MHz, CDCl3): δ 7.89 (d, J = 16.0 Hz, 1H), 7.68ꢀ7.55 (m, 3H), 7.52ꢀ7.47
(m, 6H), 7.43ꢀ7.32 (m, 3H), 7.30ꢀ7.28 (m, 2H), 7.14ꢀ7.11 (m, 2H), 6.57 (d, J = 16.5
Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.5, 146.4, 139.9, 138.1, 136.4, 136.1,
135.3, 133.1, 130.1, 129.2, 128.8, 127.8, 127.7, 127.6, 127.5, 126.6, 124.7, 122.1,
119.2; IR (thin film) 3058, 1599, 1458, 1230, 961, 750, 691 cm‒1; HRMS (ESI) m/z
calcd. for C23H19BrNO (M+H)+ 404.0650, found 404.0641; m.p:125ꢀ126 °C.
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N-((1E,4E,6E)-1,7-Diphenylhepta-1,4,6-trien-3-ylidene)aniline oxide (3n), 0.118 g,
67% yield (E/Z = 1:1), yellow solid. isomer 1: 1H NMR (500 MHz, CDCl3): δ 7.63 (d,
J = 8.0 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 7.51ꢀ7.44 (m, 6H), 7.41ꢀ7.31 (m, 4H),
7.30ꢀ7.28 (m, 2H), 7.18 (d, J = 15.5 Hz, 1H), 6.95 (d, J = 16.5 Hz, 1H), 6.83ꢀ6.80 (m,
2H), 6.61 (d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.6, 146.4, 139.4,
137.1, 136.6, 136.3, 134.4, 129.6, 129.3, 129.2, 128.9, 128.8, 128.4, 128.3, 127.5,
126.8, 124.7, 122.9, 119.3; isomer 2: 1H NMR (500 MHz, CDCl3): δ 7.61 (d, J = 8.0
Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H), 7.51ꢀ7.44 (m, 6H), 7.41ꢀ7.31 (m, 4H), 7.30ꢀ7.28 (m,
2H), 7.14 (d, J = 16.0 Hz, 1H), 7.12 (d, J = 16.0 Hz, 1H), 6.72ꢀ6.58 (m, 2H), 6.25 (d,
J = 15.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 146.7, 146.1, 140.1, 136.7, 136.6,
136.1, 135.2, 129.7, 129.3, 129.1, 128.9, 128.8, 128.4, 128.3, 126.9, 126.7, 124.8,
124.1, 120.7; IR (thin film) 3023, 1591, 1487, 1228, 971, 747, 690 cm‒1; HRMS (ESI)
m/z calcd. for C25H22NO (M+H)+ 352.1701, found 352.1699; m.p: 62ꢀ63 °C.
N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-4-methoxyaniline oxide (3ab),
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0.133 g, 74% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.63ꢀ7.60 (m, 3H),
7.53 (d, J = 16.0 Hz, 1H), 7.47 (d, J = 9.0 Hz, 2H), 7.40ꢀ7.37 (m, 2H), 7.35ꢀ7.28 (m,
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6H), 6.99 (d, J = 16.0 Hz, 1H), 6.95 (d, J = 8.5 Hz, 2H), 6.72 (d, J = 16.0 Hz, 1H),
3.86 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 160.3, 146.3, 139.8, 139.3, 136.6, 136.2,
124.5, 129.1, 129.0, 128.9, 128.8, 127.4, 126.8, 126.2, 120.9, 119.9, 114.1, 55.6; IR
(thin film) 3056, 2835, 1599, 1503, 1251, 963, 837, 762, 695 cm‒1; HRMS (ESI) m/z
calcd. for C24H22NO2 (M+H)+ 356.1651, found 356.1646; m.p: 151ꢀ153 °C.
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N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-4-methylaniline oxide (3ac),
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0.120 g, 71% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.64ꢀ7.60 (m, 3H),
7.56 (d, J = 16.5 Hz, 1H), 7.40ꢀ7.38 (m, 4H), 7.35ꢀ7.28 (m, 6H), 7.25ꢀ7.24 (m, 2H),
6.99 (d, J = 16.0 Hz, 1H), 6.70 (d, J = 16.0 Hz, 1H), 2.41 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 146.4, 144.2, 139.9, 139.4, 136.6, 136.2, 134.5, 129.7, 129.1, 129.0,
128.9, 128.8, 127.4, 126.9, 124.5, 120.8, 119.7, 21.3; IR (thin film) 3057, 2950, 1602,
1499, 1230, 964, 762, 695 cm‒1; HRMS (ESI) m/z calcd. for C24H22NO (M+H)+
340.1701, found 340.1697; m.p: 170ꢀ171 °C.
4-tert-Butyl-N-((1E,4E)-1,5-diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3ad),
1
0.148 g, 78% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.65ꢀ7.61 (m, 3H),
7.54 (d, J = 16.5 Hz, 1H), 7.47ꢀ7.43 (m, 4H), 7.41ꢀ7.38 (m, 2H), 7.35ꢀ7.28 (m, 7H),
7.01 (d, J = 16.0 Hz, 1H), 6.72 (d, J = 16.5 Hz, 1H), 1.35 (s, 9H); 13C NMR (125
MHz, CDCl3): δ 153.1, 146.6, 144.0, 139.5, 136.5, 136.2, 134.8, 129.7, 129.1, 128.9,
128.8, 127.5, 126.9, 126.1, 124.3, 120.8, 119.8, 31.2; IR (thin film) 3053, 2867, 1604,
1499, 1381, 1235, 966, 752, 691 cm‒1; HRMS (ESI) m/z calcd. for C27H28NO (M+H)+
382.2171, found 382.2149; m.p: 150ꢀ152 °C.
4-Chloro-N-((1E,4E)-1,5-diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3ae),
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0.127 g, 71% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.62ꢀ7.57 (m, 4H),
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(125 MHz, CDCl3): δ 147.0, 144.8, 140.1, 136.3, 135.8, 135.6, 135.5, 129.4, 129.3,
129.1, 128.9, 128.8, 127.5, 126.9, 126.1, 120.1, 119.4; IR (thin film) 3059, 1614,
1448, 1229, 967, 757, 695 cm‒1; HRMS (ESI) m/z calcd. for C23H19ClNO (M+H)+
360.1155, found 360.1149; m.p: 169ꢀ170 °C.
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N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-4-fluoroaniline oxide (3af),
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0.125 g, 73% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.63ꢀ7.60 (m, 3H),
7.56 (d, J = 16.5 Hz, 1H), 7.53ꢀ7.51 (m, 2H), 7.41ꢀ7.38 (m, 2H), 7.36ꢀ7.30 (m, 6H),
7.17 (t, J = 8.5 Hz, 2H), 7.01 (d, J = 16.0 Hz, 1H), 6.65 (d, J = 16.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ 163.6 (d, J = 249.6 Hz), 146.8, 142.6 (d, J = 3.6 Hz),
139.9, 136.3, 135.8, 135.3, 129.2 (d, J = 31 Hz), 128.9, 128.8, 127.5, 126.9, 126.8,
126.7, 120.2, 119.4, 116.2 (d, J = 23 Hz); IR (thin film) 3061, 1598, 1498, 1228, 967,
760, 695 cm‒1; HRMS (ESI) m/z calcd. for C23H19FNO (M+H)+ 344.1451, found
344.1436; m.p: 180ꢀ182 °C.
N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-3-nitroaniline oxide (3ag),
0.120 g, 65% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 8.44 (s, 1H), 8.33 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.65ꢀ7.62 (m, 4H), 7.43ꢀ7.36 (m, 4H),
7.32ꢀ7.31 (m, 5H), 7.07 (d, J = 16.5 Hz, 1H), 6.60 (d, J = 16.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ 148.5, 147.7, 147.0, 141.0, 137.0, 136.1, 135.5, 130.6, 130.2,
129.6, 129.4, 129.0, 128.9, 127.7, 127.0, 124.3, 120.4, 119.3, 119.1; IR (thin film)
3058, 1651, 1576, 1228, 967, 753, 692 cm‒1; HRMS (ESI) m/z calcd. for C23H19N2O3
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(M+H)+ 371.1396, found 371.1376; m.p: 135ꢀ136 °C.
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oxide
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(3ah), 0.123 g, 70% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.63 (d, J =
7.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.41ꢀ7.38 (m, 2H), 7.35ꢀ7.29 (m, 6H), 7.09 (s,
2H), 7.07 (s, 1H), 6.99 (d, J = 16.0 Hz, 1H), 6.69 (d, J = 16.5 Hz, 1H), 2.34 (s, 6H);
13C NMR (125 MHz, CDCl3): δ 146.3, 139.5, 139.2, 136.6, 136.2, 134.4, 131.3, 129.1,
128.9, 128.8, 128.7, 127.5, 126.9, 122.2, 120.7, 119.4, 21.2; IR (thin film) 3018, 2919,
2863, 1594, 1472, 1272, 960, 756, 692 cm‒1; HRMS (ESI) m/z calcd. for C25H24NO
(M+H)+ 354.1858, found 354.1837; m.p: 138ꢀ139 °C.
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N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-2-methylaniline oxide (3ai),
0.110 g, 65% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.70 (d, J = 16.5 Hz,
1H), 7.64ꢀ7.61 (m, 3H), 7.41ꢀ7.38 (m, 2H), 7.36ꢀ7.34 (m, 2H), 7.32ꢀ7.31 (m, 3H),
7.28ꢀ7.25 (m, 3H), 7.23 (d, J = 7.5 Hz, 2H), 7.00 (d, J = 16.0 Hz, 1H), 6.49 (d, J =
16.0 Hz, 1H), 2.31 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 146.7, 145.2, 139.6, 136.4,
136.0, 134.8, 131.9, 131.4, 129.4, 129.1, 128.9, 128.8, 127.9, 127.4, 127.1, 126.8,
124.3, 119.4, 118.3, 16.9; IR (thin film) 3058, 2926, 1609, 1576, 1449, 1229, 965, 759,
695 cm‒1; HRMS (ESI) m/z calcd. for C24H22NO (M+H)+ 340.1701, found 340.1683;
m.p: 169ꢀ170 °C.
N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-4-(trifluoromethyl)aniline
oxide (3aj), 0.114 g, 58% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.75 (d,
J = 8.5 Hz, 2H), 7.66ꢀ7.60 (m, 5H), 7.45ꢀ7.31 (m, 9H), 7.05 (d, J = 16.0 Hz, 1H), 6.62
(d, J = 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 148.8, 147.4, 140.6, 136.3,
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136.2, 135.6, 132.0 (q, J = 32 Hz), 129.5, 129.2, 128.9, 128.8, 127.6, 126.9, 126.5 (q,
J = 3.6 Hz), 125.3, 124.5 (q, J = 270.6 Hz), 119.6, 119.1; IR (thin film) 3018, 1619,
1574, 1487, 1229, 951, 766, 694 cm‒1; HRMS (ESI) m/z calcd. for C24H19F3NO
(M+H)+ 394.1419, found 394.1398; m.p: 147ꢀ148 °C.
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4-Bromo-N-((1E,4E)-1,5-diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3ak),
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0.137 g, 68% yield, yellow solid. H NMR (500 MHz, CDCl3): δ 7.62ꢀ7.57 (m, 6H),
7.42ꢀ7.38 (m, 4H), 7.36ꢀ7.32 (m, 6H), 7.02 (d, J = 16.0 Hz, 1H), 6.65 (d, J = 16.0 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 146.9, 145.3, 140.1, 136.3, 135.8, 135.6, 132.4,
129.3, 129.1, 128.9, 128.8, 127.5, 126.9, 126.4, 123.6, 120.1, 119.4; IR (thin film)
3057, 1579, 1481, 1228, 965, 756, 694 cm‒1; HRMS (ESI) m/z calcd. for C23H19BrNO
(M+H)+ 404.0650, found 404.0648; m.p: 173ꢀ174 °C.
3-Bromo-N-((1E,4E)-1,5-diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3al),
0.145 g, 72% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.72 (s, 1H), 7.63 (d,
J = 7.0 Hz, 2H), 7.59ꢀ7.58 (m, 3H), 7.42ꢀ7.31 (m, 10H), 7.02 (d, J = 16.0 Hz, 1H),
6.64 (d, J = 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 147.2, 147.0, 140.2, 136.2,
135.8, 135.7, 132.8, 130.3, 129.3, 129.1, 128.9, 128.8, 128.0, 127.5, 126.9, 123.3,
122.7, 119.9, 119.1; IR (thin film) 3042, 1577, 1452, 1226, 964, 755, 692 cm‒1;
HRMS (ESI) m/z calcd. for C23H19BrNO (M+H)+ 404.0650, found 404.0628; m.p:
149ꢀ151 °C.
2-Bromo-N-((1E,4E)-1,5-diphenylpenta-1,4-dien-3-ylidene)aniline oxide (3am),
0.177 g, 88% yield, yellow solid. 1H NMR (500 MHz; CDCl3): δ 7.74 (d, J = 17.0 Hz,
1H), 7.70 (d, J = 8.0 Hz, 1H), 7.64ꢀ7.61 (m, 3H), 7.48ꢀ7.45 (m, 2H), 7.41ꢀ7.25 (m,
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9H), 7.03 (d, J = 16.0 Hz, 1H), 6.45 (d, J = 16.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ 147.3, 145.2, 140.3, 136.4, 135.9, 133.9, 130.5, 129.3, 129.0, 128.9, 128.8,
128.4, 128.3, 127.6, 126.9, 126.3, 119.0, 118.1, 117.4; IR (thin film) 3045, 3001, 1604,
1574, 1477, 1238, 973, 754, 689 cm‒1; HRMS (ESI) m/z calcd. for C23H19BrNO
(M+H)+ 404.0650, found 404.0625; m.p: 126ꢀ128 °C.
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N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)thiophen-3-amine oxide (3an),
0.073 g, 44% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.65 (d, J = 17.0 Hz,
1H), 7.62 (d, J = 8.0 Hz, 2H), 7.53ꢀ7.48 (m, 2H), 7.40ꢀ7.31 (m, 10H), 7.03 (d, J =
16.0 Hz, 1H), 6.87 (d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 147.1, 144.8,
139.9, 136.4, 135.9, 135.4, 129.2, 129.0, 128.9, 128.8, 127.5, 126.9, 125.8, 124.4,
121.4, 120.3, 119.7; IR (thin film) 3040, 1614, 1574, 1448, 1232, 966, 760, 693 cm‒1;
HRMS (ESI) m/z calcd. for C21H18SNO (M+H)+ 332.1109, found 332.1092; m.p:
154ꢀ156 °C.
N-((1E,4E)-1,5-Diphenylpenta-1,4-dien-3-ylidene)-4-(methoxycarbonyl)aniline
oxide (3ao), 0.155 g, 81% yield, yellow solid. 1H NMR (500 MHz, CDCl3): δ 8.16 (d,
J = 8.5 Hz, 2H), 7.63ꢀ7.57 (m, 6H), 7.42ꢀ7.34 (m, 4H), 7.33ꢀ7.27 (m, 5H), 7.03 (d, J =
16.0 Hz, 1H), 6.62 (d, J = 16.0 Hz, 1H), 3.95 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
165.8, 149.5, 147.1, 140.3, 136.2, 135.8, 135.7, 131.1, 130.7, 129.4, 129.1, 128.9,
128.8, 127.5, 126.9, 124.9, 119.9, 119.2, 52.4; IR (thin film) 3054, 2949, 1721, 1601,
1279, 964, 757, 695 cm‒1; HRMS (ESI) m/z calcd. for C25H22NO3 (M+H)+ 384.1600,
found 384.1593; m.p: 101ꢀ102 °C.
N-((E)-1,3-Diphenylallylidene)aniline oxide (3o), 0.097 g, 65% yield (E/Z = 10:1),
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yellow solid. Eꢀisomer (Major): H NMR (500 MHz, CDCl3): δ 8.19 (d, J = 16.5 Hz,
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1H), 7.56ꢀ7.52 (m, 3H), 7.35ꢀ7.27 (m, 7H), 7.22ꢀ7.16 (m, 5H), 6.72 (d, J = 16.5 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ 149.7, 147.0, 140.6, 136.2, 132.7, 130.7, 129.2,
128.8, 128.7, 128.6, 128.5, 128.3, 127.6, 124.8, 121.9; Zꢀisomer (minor) based on: 1H
NMR (500 MHz, CDCl3): δ 6.92 (d, J = 16.0 Hz, 1H), 6.42 (d, J = 16.0 Hz, 1H); IR
(thin film) 3051, 1592, 1497, 1235, 971, 768, 693 cm‒1; HRMS (ESI) m/z calcd. for
C21H18NO (M+H)+ 300.1388, found 300.1368; m.p: 104ꢀ105 °C.
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N-((E)-3-(4-Methoxyphenyl)-1-phenylallylidene)aniline oxide (3p), 0.069 g, 42%
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yield (E/Z = 12:1), yellow solid. Eꢀisomer (Major): H NMR (500 MHz, CDCl3): δ
8.07 (d, J = 16.0 Hz, 1H), 7.49 (d, J = 9.0 Hz, 2H), 7.27ꢀ7.26 (m, 5H), 7.19ꢀ7.16 (m,
5H), 6.88 (d, J = 8.5 Hz, 2H), 6.67 (d, J = 16.5 Hz, 1H), 3.82 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 160.7, 150.1, 147.0, 140.6, 132.9, 130.8, 130.0, 129.2, 129.1, 128.8,
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128.5, 128.3, 124.9, 119.9, 114.2, 55.3; Zꢀisomer (minor) based on: H NMR (500
MHz, CDCl3): δ 6.36 (d, J = 15.5 Hz, 1H), 3.76 (s, 3H); IR (thin film) 3053, 2836,
1590, 1509, 1239, 974, 760, 696 cm‒1; HRMS (ESI) m/z calcd. for C22H20NO2
(M+H)+ 330.1494, found 330.1490; m.p: 112ꢀ113 °C.
N-((E)-1,3-Diphenylallylidene)-4-methoxyaniline oxide (3q), 0.087 g, 53% yield
(E/Z = 8:1), yellow solid. Eꢀisomer (Major): 1H NMR (500 MHz, CDCl3): δ 8.16 (d, J
= 16.5 Hz, 1H), 7.53 (d, J = 7.0 Hz, 2H), 7.35ꢀ7.28 (m, 8H), 7.21ꢀ7.17 (m, 4H),
6.70ꢀ6.67 (m, 3H), 3.73 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 159.3, 149.2, 140.2,
136.3, 133.1, 130.7, 129.1, 128.8, 128.7, 128.4, 127.5, 126.1, 122.3, 114.3, 113.5,
55.3; Zꢀisomer (minor) based on: 1H NMR (500 MHz, CDCl3): δ 6.40 (d, J = 16.0 Hz,
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1H), 3.89 (s, 3H); IR (thin film) 3034, 2836, 1603, 1501, 1238, 971, 752, 693 cm‒1;
HRMS (ESI) m/z calcd. for C22H20NO2 (M+H)+ 330.1494, found 330.1487; m.p:
155ꢀ157 °C.
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N-((E)-1,3-Diphenylallylidene)-2-methylaniline oxide (3r), 0.049 g, 31% yield (E/Z
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= 8:1), yellow solid. Eꢀisomer (Major): H NMR (500 MHz, CDCl3): δ 8.24 (d, J =
16.5 Hz, 1H), 7.53 (d, J = 7.0 Hz, 2H), 7.34ꢀ7.27 (m, 3H), 7.24ꢀ7.23 (m, 3H),
7.17ꢀ7.16 (m, 2H), 7.09ꢀ7.08 (m, 3H), 7.01ꢀ6.98 (m, 1H), 6.69 (d, J = 16.5 Hz, 1H),
2.36 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 150.4, 145.7, 140.7, 136.0, 132.0, 131.6,
130.9, 129.9, 129.2, 128.9, 128.6, 128.5, 128.1, 127.5, 126.0, 125.0, 121.1, 17.2; IR
(thin film) 3058, 2933, 2858, 1599, 1496, 1271, 968, 772, 695 cm‒1; HRMS (ESI) m/z
calcd. for C22H20NO (M+H)+ 314.1545, found 314.1534; m.p: 62ꢀ63 °C.
(1E,2E)-Chalcone O-phenyl oxime (4a) was prepared from Table 1 entry 2 with 40%
yield as yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.59 (d, J = 7.5 Hz, 2H), 7.55 (d,
J = 7.5 Hz, 2H), 7.49 (d, J = 17.0 Hz, 1H), 7.42ꢀ7.30 (m, 10H), 7.27ꢀ7.24 (m, 1H),
7.18 (d, J = 16.5 Hz, 1H), 7.06 (t, J = 7.0 Hz, 1H), 7.02 (d, J = 16.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ 159.4, 156.6, 138.3, 136.4, 136.3, 136.0, 129.2, 128.9,
128.8, 128.7, 127.5, 127.4, 127.1, 122.4, 121.6, 117.4, 115.0; IR (thin film) 3033,
1588, 1485, 1212, 969, 753, 690 cm‒1; HRMS (ESI) m/z calcd. for C23H20NO (M+H)+
326.1545, found 326.1536; m.p: 88ꢀ89 °C.
(E)-4-Phenyl-2-styrylquinoline (5)31 was prepared as follow. Nitrone 3a (0.065 g,
0.20 mmol) was dissolved in toluene (2 mL), and the mixture was stirring at 100 ˚C.
The reaction was monitored by TLC until the nitrone was consumed completely. At
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this time, the toluene was removed under reduced pressure and crude product was
purified by flash chromatography (the crude residue was dryꢀloaded on silica gel; 1:20
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ethyl acetate:petroleum ether) to afford 5 as yellow oil (0.033g, 56%). H NMR (500
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MHz, CDCl3): δ 7.61 (d, J = 7.5 Hz, 2H), 7.52 (s, 1H), 7.41 (t, J = 7.5 Hz, 2H),
7.35ꢀ7.30 (m, 7H), 7.21 (d, J = 16.5 Hz, 1H), 7.13ꢀ7.10 (m, 1H), 6.93 (d, J = 7.5 Hz,
2H), 6.78 (d, J = 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ 162.9, 150.7, 138.4,
138.0, 136.1, 135.7, 129.7, 129.2, 129.0, 128.9, 128.8, 128.7, 128.6, 127.5, 127.3,
125.9, 123.8, 122.3, 120.9; IR (thin film) 3055, 1620, 1591, 1493, 1284, 974, 757,
694 cm‒1.
(E)-N-Phenyl-N-styryl-N'-p-tolylcinnamimidamide (6) was prepared as follow.
Nitrone 3a (0.065 g, 0.20 mmol) and isocyanate (0.079 mg, 0.6 mmol) were dissolved
in toluene (2 mL). The mixture was stirring at 80 ˚C. The reaction was monitored by
TLC until the nitrone was consumed completely. At this time, the toluene was
removed under reduced pressure and crude product was purified by flash
chromatography (the crude residue was dryꢀloaded on silica gel; 1:20 ethyl
acetate:petroleum ether) to afford 6 as yellow oil (0.079g, 96%). 1H NMR (500 MHz,
CDCl3): δ 8.08 (d, J = 14.5 Hz, 1H), 7.41ꢀ7.38 (m, 2H), 7.33 (d, J = 7.5 Hz, 2H),
7.27ꢀ7.18 (m, 8H), 7.09ꢀ7.05 (m, 3H), 6.98ꢀ6.97 (m, 2H), 6.85 (d, J = 7.5 Hz, 2H),
6.58 (d, J = 16.0 Hz, 1H), 6.18 (d, J = 16.5 Hz, 1H), 5.66 (d, J = 14.5 Hz, 1H), 2.30 (s,
3H); 13C NMR (125 MHz, CDCl3): δ 154.6, 147.3, 141.6, 140.4, 137.4, 135.6, 132.4,
131.9, 129.4, 129.3, 128.8, 128.6, 128.5, 128.4, 126.9, 126.8, 125.6, 125.3, 121.9,
119.1, 112.1, 20.8; IR (thin film) 3027, 2924, 2858, 1638, 1495, 1327, 746, cm‒1;
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