Reactions of 3,3,3-Trihalogeno-1-nitropropenes with Arenes in the Superacid CF3SO3H: Synthesis of (Z)-3,3,3-Trihalogeno-1,2-diarylpropan-1-one Oximes and Study on the Reaction Mechanism

Article abstract of DOI:10.1021/acs.joc.8b01406

3,3,3-Trihalogeno-1-nitropropenes C(Hal₃)CH=CH(NO₂) (Hal = F, Cl, Br) in reaction with arenes in the superacid CF₃SO₃H (TfOH) at room temperature in 1 h afford 3,3,3-trihalogeno-1,2-diarylpropan-1-one oximes C(Hal₃)CH(Ar)-C(Ar)=NOH (CHal₃-oximes) in yields of 23-99%. Such CHal₃-oximes having one ortho-substituent in the aryl ring exist as atropoisomers in solutions at room temperature. Several cationic intermediates of this reaction were studied by means of NMR and DFT calculations, which proves the detailed reaction mechanism of the formation of CHal₃-oximes in TfOH. CHal₃-oximes (for Hal = Cl, Br) with DBU in DMF at microwave or thermal activation are cyclized into 5-halogeno-3,4-diarylisoxazoles in yields of 37-59%. CHal₃-oximes under the conditions of Beckmann rearrangement with PCl₅ in benzene at room temperature in 24 h are turned at first into imidoyl chlorides (yields of 94-96%), which undergo transformation into the corresponding benzamides PhCONHCHPh(CHal₃) on silica gel (yields of 46-47%).

Full text of DOI:10.1021/acs.joc.8b01406

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Article
Reactions of 3,3,3-trihalogeno-1-nitropropenes with arenes in
the superacid CF3SO3H: synthesis of (Z)-3,3,3-trihalogeno-1,2-
diarylpropan-1-one oximes and study on the reaction mechanism
Andrei A. Golushko, Maria A. Sandzhieva, Alexander Yu. Ivanov, Irina A. Boyarskaya,
Olesya V Khoroshilova, Alexey Yu. Barkov, and Aleksander Viktorovich Vasilyev
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01406 • Publication Date (Web): 13 Jul 2018
Downloaded from http://pubs.acs.org on July 14, 2018
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Reactions of 3,3,3ꢀtrihalogenoꢀ1ꢀnitropropenes with arenes in the superacid
CF3SO3H: synthesis of (Z)ꢀ3,3,3ꢀtrihalogenoꢀ1,2ꢀdiarylpropanꢀ1ꢀone oximes
and study on the reaction mechanism
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Andrei A. Golushko,1 Maria A. Sandzhieva,2 Alexander Yu. Ivanov,3 Irina A. Boyarskaya,1
Olesya V. Khoroshilova,4 Alexey Yu. Barkov,5 Aleksander V. Vasilyev1,2*
1 Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University,
Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia
2 Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5, Saint
Petersburg, 194021, Russia
3Center for Magnetic Resonance, Research Park, St. Petersburg State University, Universitetskiy pr., 26,
Saint Petersburg, Petrodvoretz, 198504 , Russia
4Center for X-ray Diffraction Studies, Research Park, St. Petersburg State University, Universitetskiy pr.,
26, Saint Petersburg, Petrodvoretz, 198504 , Russia
5Institute of Natural Sciences and Mathematics, Ural Federal University, Mira str., 19, Yekaterinburg,
620000, Russia
*Corresponding author: A.V. Vasilyev; e-mails: aleksvasil@mail.ru; a.vasilyev@spbu.ru
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Keywords: 3,3,3ꢀtrihalogenoꢀ1ꢀnitropropenes, 3,3,3ꢀtrihalogenoꢀ1,2ꢀdiarylpropanꢀ1ꢀone oximes,
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atropoisomers, cations, superacids
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Graphical Abstract
H
Hal3C
Hal3C
TfO
N OH
Hal3C
Ar
N OH
Ar
Hal3C
H2O
NO2H
TfOH, ArH
NO2
OTf
Hal3C
Ar
H
regio- and atropo- isomers
Hal3C
Ar
N OH
Ar
N
OH
Hal = F, Cl, Br
23-99%
HO
20 examples
NMR study of intermediate cations
Abstract
3,3,3ꢀTrihalogenoꢀ1ꢀnitropropenes C(Hal3)CH=CH(NO2) (Hal = F, Cl, Br) in reaction with arenes in the
superacid CF3SO3H (TfOH) at room temperature in 1 h afford 3,3,3ꢀtrihalogenoꢀ1,2ꢀdiarylpropanꢀ1ꢀone
oximes C(Hal3)CH(Ar)–C(Ar)=NOH (CHal3ꢀoximes) in yields of 23ꢀ99%. Such CHal3ꢀoximes having
one orthoꢀsubstituent in aryl ring exist as atropoisomers in solutions at room temperature. Several cationic
intermediates of this reaction were studied by means of NMR and DFT calculations, that proves the
detailed reaction mechanism of the formation of CHal3ꢀoximes in TfOH. CHal3ꢀoximes (for Hal = Cl, Br)
with DBU in DMF at microwave or thermal activation are cyclized into 5ꢀhalogenoꢀ3,4ꢀdiarylisoxazoles
in yields of 37ꢀ59%. CHal3ꢀoximes under the conditions of Beckmann rearrangement with PCl5 in
benzene at room temperature in 24 h are turned at first into imidoyl chlorides (yields of 94ꢀ96%), which
undergo transformation into the corresponding benzamides PhCONHCHPh(CHal3) on silica gel (yields of
46ꢀ47 %).
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INTRODUCTION
Conjugated nitroalkenes are versatile reagents in organic synthesis.1 Their reactions with
nucleophiles allow to obtain various heterocycles, functional derivatives, and many other compounds
including biologically active ones.1ꢀ3 Nitroalkenes are used as alkylating agents in reactions with arenes
and heteroarenes promoted by Brønsted superacids4,5 or Lewis acids.6
In the series of studies on reactions of nitroalkenes with arenes in triflic acid CF3SO3H (TfOH),4
Ohwada and Shudo postulated the formation of O,O'ꢀdiprotonated forms of nitroalkenes, which finally led
to the corresponding 1,2ꢀdiaryl oximes (Scheme 1). Such diprotonated species were studied by means of
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NMR by Ohwada and Shudo,4 and Coustard.5
HO
R
N
OH
R
NO2
R
N
OH
2H+ (TfOH)
2ArH
Ar
-2H+, -H2O
R'
R'
Ar
R'
R, R'= H, Me, Ph
Scheme 1. Reactions of nitroalkenes with arenes in TfOH with intermediate formation of O,Oꢀ
diprotonated forms of nitroalkenes leading to the corresponding oximes (data from ref. 4).
Based on our work on superelectrophilic activation of unsaturated compounds,7 we have decided to
undertake a special study on reactions of (E)ꢀ3,3,3ꢀtrihalogenoꢀ1ꢀnitropropenes (CHal3ꢀnitroethylenes) 1aꢀ
c (Figure 1) under the action of Brønsted and Lewis acids. The presence of functional trihalogenometyl
group in products of reactions of 1aꢀc, especially CCl3 and CBr3, gives opportunities for further synthetic
transformations of the obtained substrates.
F3C
Cl3C
Br3C
NO2
NO2
NO2
1a
1b
1c
Figure 1. (E)ꢀ3,3,3ꢀTrihalogenoꢀ1ꢀnitropropenes 1aꢀc used in this study.
3,3,3ꢀTrihalogenoꢀ1ꢀnitropropenes 1aꢀc are useful and perspective building blocks for synthesis of
carboꢀ and heterocycles, spirocompounds, etc.8 However, there is just one publication9 from 1963 on the
reaction of CCl3ꢀnitroethylene 1b with benzene under the action of AlCl3 in CH2Cl2 that gave oxime of
3,3,3ꢀtrichloroꢀ1,2ꢀdiphenylpropanꢀ1ꢀone in yield of 35 %.
The main goals of this work are (a) study of reactions of CHal3ꢀnitroethylenes 1aꢀc with arenes
under superelectrophilic activation conditions in TfOH leading to the formation of 3,3,3ꢀtrihalogenoꢀ1,2ꢀ
diarylpropanꢀ1ꢀone oximes, (b) investigation of cationic intermediates of these transformations by means
of NMR and theoretical DFT calculations, (c) elucidation of reaction mechanism, and (d) synthesis of
organic compounds from 3,3,3ꢀtrihalogenoꢀ1,2ꢀdiarylpropanꢀ1ꢀone oximes.
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RESULTS AND DISCUSSION
Reactions of CHal3-nitroethylenes 1a-c with arenes.
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Reactions of CHal3ꢀnitroethylenes 1aꢀc with various arenes were carried out under the action of
Brønsted (TfOH, H2SO4) or Lewis (AlCl3, AlBr3) acids. Tables 1, 2, and 3 contain data on reactions of
CF3ꢀnitroethylene 1a, CCl3ꢀnitroethylene 1b, and CBr3ꢀnitroethylene 1c leading to the corresponding Zꢀ
isomers of 1,2ꢀdiaryl oximes 2, 3, and 4 respectively. Structures of some reaction products 2ꢀ4 were
additionally confirmed by Xꢀray analysis (Figure 2).
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The best results were obtained with the use of excess of TfOH at room temperature for 1 h. Under
these conditions, reactions of compounds 1aꢀc with benzene proceeded with quantitative formation of the
corresponding 1,2ꢀdiphenyloximes (2a, entry 1, Table 1; 3a, entry 1, Table 2; 4a, entry 1, Table 3; see Xꢀ
ray of 2a, 3a, 4a in Supporting Information). However, the use of less amount of TfOH (10% mol.) in
solution of CH2Cl2 gave complex mixture of the reaction products (entry 5, Table 1). In the case of CF3ꢀ
(1a) and CCl3ꢀ (1b) nitroethylenes, the corresponding oximes were obtained in reactions with the
following arenes: 1,3,5ꢀtrimethylbenzene (mesitylene) (2f, entry 10, Table 1; 3c, entry 5, Table 2),
1,2,4,5ꢀtetramethylbenzene (durene) (2h, entry 12, Table 1, see Xꢀray in Supporting Information; 3d1,
3d2, entry 6, Table 2), 1,2ꢀdimethoxybenzene (veratrole) (2k, entry 17, Table 1; 3f, entry 8, Table 2). On
the other hand, CBr3ꢀnitroethylene 1c formed complex mixtures with methylbenzene (toluene),
mesitylene, durene and methoxybenzene (anisole (Table 3), but with veratrole it gave oxime 4с (entry 8,
Table 3). CF3ꢀNitroethylene 1a afforded mixtures of regioꢀ and/or atropoisomers of oximes (vide infra) in
reactions with toluene (2b), 1,2ꢀdimethylbenzene (orthoꢀxylene) (2d), 1,3ꢀdimethylbenzene (metaꢀxylene)
(2e), 1,4ꢀdimethylbenzene (paraꢀxylene) (2c), 1,2,4ꢀtrimethylbenzene (pseudocumene) (2g),
fluorobenzene (2i), anisole (2j) (Table 1).
CCl3ꢀNitroethylene 1b gave a complex mixture of products in reaction with toluene (entry 3, Table
2). Contrary to that, reaction with anisole resulted in the formation of two regioisomers 3e1 and 3e2 (see
Xꢀray in Supporting Information), in which para-methoxyphenyl rings have been located at carbon С2
(entry 7, Table 2). That indicates substantial steric demands from the CCl3ꢀgroup on regioselectivity of
interaction of intermediate cationic species with arenes at carbon C2. Apart from that, 1b furnished two
structural isomers 3d1 and 3d2 in reaction with durene (entry 6, Table 2). One of them, 3d2 (see Xꢀray in
Supporting Information), was formed as a result of methyl group shifts in tetramethyl substituted aromatic
ring at C2. The most likely, the shifts were caused by steric hindrance from large CCl3ꢀgroup. Also, the
formation of complex mixtures in reactions of CBr3ꢀnitroethylene 1c with sterically hindered substrates,
mesitylene and durene, is most probably due to a big spatial size of CBr3ꢀgroup (Table 3).
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Apart from TfOH, other acids were tested in this reaction. Thus, the use of H2SO4 led to water
soluble products (entry 4, Table 1) and did not give any oximes. Aluminum halogenides, AlCl3 and AlBr3,
were found to be not so effective; the yields of oximes 2a (entries 2 and 3, Table 1), 3a (entry 2, Table 2),
and 4a (entry 2, Table 3) were 7ꢀ75%.
Table 1. Reactions of CF3ꢀnitroethylene 1a with arenes under the action of Brønsted and Lewis acids.
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Entry
1
Arene, ArH
benzene
Reaction conditions
TfOH (excess), CH2Cl2, r.t., 1 h
Reaction product, yield %
Zꢀ2a, 97%
2
3
4
benzene
benzene
benzene
AlCl3 (5 equiv.), r.t., 0.5 h
AlBr3 (5 equiv.), r.t., 0.5 h
H2SO4 (excess), 1 h
Zꢀ2a, 47%
Zꢀ2a, 7%
complex mixture
5
benzene
TfOH (10% mol.), CH2Cl2, r.t.,
1 h
complex mixture
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methylbenzene
TfOH (excess), CH2Cl2, r.t., 1 h
9 regioꢀ and atropoisomers
Zꢀ2b, 84%
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1,4ꢀdimethylbenzene
1,2ꢀdimethylbenzene
1,3ꢀdimethylbenzene
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ2c, 94%
2 atropoisomers
4 regioꢀ and atropoisomers
Zꢀ2d, 77%
4 regioꢀ and atropoisomers
Zꢀ2e, 85%
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1,3,5ꢀtrimethylbenzene
1,2,4ꢀtrimethylbenzene
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ2f, 96%
TfOH (excess), CH2Cl2, r.t., 1 h
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6 regioꢀ and atropoisomers
Zꢀ2g, 39%
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13
1,2,4,5ꢀtetramethylbenzene TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ2h, 71%
fluorobenzene
TfOH (excess), CH2Cl2, r.t., 1 h
3 regioꢀ and atropoisomers
Zꢀ2i, 84%
14
chlorobenzene
TfOH (excess), CH2Cl2, r.t., 1 h
complex mixture
15
16
1,2ꢀdichlorobenzene
methoxybenzene
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
complex mixture
6 regioꢀ and atropoisomers
Zꢀ2j, 63%
17
1,2ꢀdimethoxybenzene
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ2k, 59%
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Table 2. Reactions of CCl3ꢀnitroethylene 1b with arenes under the action of Brønsted and Lewis acids.
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Entry
1
Arene, ArH
benzene
Reaction conditions
TfOH (excess), CH2Cl2, r.t., 1 h
Reaction product, yield %
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Zꢀ3a, 99%
Zꢀ3a, 75%
complex mixture
2
3
4
benzene
methylbenzene
1,4ꢀdimethylbenzene
AlCl3 (5 equiv.), r.t., 0.5 h
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
2 atropoisomers
Zꢀ3b, 49%
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6
1,3,5ꢀtrimethylbenzene
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ3c, 65%
Cl3C
1,2,4,5ꢀtetramethylbenzene TfOH (excess), CH2Cl2, r.t., 1 h
N
OH
CH3
H3C
H3C
H3C
CH3
CH3
CH3
H3C
Z-3d1
Cl3C
N
OH
CH3
H3C
H3C
H3C
CH3
CH3
CH3
H3C
Z-3d2
Zꢀ3d1 : Zꢀ3d2 0.8 : 1, 50%
N OH
Cl3C
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methoxybenzene
TfOH (excess), CH2Cl2, r.t., 1 h
H3CO
OCH3
Z-3e1
N OH
OCH3
Cl3C
H3CO
Z-3e2
Zꢀ3e1 : Zꢀ3e2 1 : 0.5, 40%
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1,2ꢀdimethoxybenzene
TfOH (excess), CH2Cl2, r.t., 1 h
4
5
6
7
Zꢀ3f, 42%
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Table 3. Reactions of CBr3ꢀnitroethylene 1c with arenes under the action of Brønsted and Lewis acids.
Entry
1
Arene, ArH
benzene
Reaction conditions
Reaction product, yield %
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ4a, 95%
Zꢀ4a, 47%
2
benzene
AlCl3 (5 equiv.), r.t., 0.5 h
3
4
methylbenzene
1,4ꢀdimethylbenzene
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
complex mixture
2 atropoisomers
Zꢀ4b, 48%
5
6
7
8
1,3,5ꢀtrimethylbenzene
1,2,4,5ꢀtetramethylbenzene TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
complex mixture
complex mixture
complex mixture
methoxybenzene
1,2ꢀdimethoxybenzene
TfOH (excess), CH2Cl2, r.t., 1 h
TfOH (excess), CH2Cl2, r.t., 1 h
Zꢀ4c, 23%
These reactions can be done in larger scale as well (Scheme 2).
F3C
Ph
N OH
Ph
F3C
TfOH (2 mL)
(1.5 mL, 0.017 mol)
PhH
NO2
1a
Z-2a (960 mg, 97%)
(500 mg, 1.55 mmol)
Scheme 2. Large scale reaction of 1a with benzene in TfOH leading to oxime Zꢀ2a.
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Atropoisomerism of oximes 2-4.
Reactions of CHal3ꢀnitroethylenes 1aꢀc with paraꢀxylene resulted in the formation of oximes 2c, 3b,
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4b respectively. Double set of signals with different integral ratio was observed in H, C, F (for 2c)
NMR spectra of these compounds in CDCl3 at room temperature (see experimental part and Supporting
Information). In this regard, it was suggested that for these and other oximes an atropoisomeric
equilibrium may exist in solution due to the restricted rotation of the bulky CHal3 group and aryl
substituents.
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To check this hypothesis, 1H, 19F (for 2c) NMR spectra of 2c, 3b, 4b were recorded in DMSOꢀD6 at
different temperatures from 25 to 120°C. Upon increasing temperature, it was observed, a broadening of
NMR signals, followed by their coalescence and again narrowing (Figure 2, see other spectra in
Supporting Information). Coalescence was not experimentally achieved for CBr3ꢀoxime 4b. The values of
the coalescence temperature and activation energies (barriers) for transformations of atropoisomers 2c, 3b,
4b are shown in table 4 (see experimental part for details of calculations). These data clearly show that on
increasing size of halogen (F→Cl→Br) the activation barrier of transition between atropoisomers is
increased.
120°С
N
OH
CH3
F3C
2
1
H3C
100°С
Cipso-
90°С
80°С
H3C
CH3
70°С
60°С
50°С
Z-2c
40°С
30°С
25°С
Figure 2. Fragments of H NMR spectra of oxime 2с (signals of proton H2) in DMSOꢀD6 at different
1
temperatures (400 MHz).
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Table 4. Coalescence temperature and activation energy for atropoisomeric transitions for oximes 2c, 3b,
4b according to NMR data.
5
6
7
8
Oxime
Coalescence
temperature, °C
Activation energy,
kJ/mol
N
OH
CH3
F3C
2
1
H3C
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10
11
12
13
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15
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~ 85
58.6
H3C
CH3
Z-2c
Zꢀ2c
Cl3C
N
OH
CH3
H3C
~ 120
68.6
70.3
CH
3H3C
Zꢀ3b
Br3C
N
OH
CH3
H3C
–
CH
3H3C
Zꢀ4b
Quantum chemical calculations of rotation barriers in oxime 2c have been carried out to figure out at
which bond this rotation takes place. It was calculated that rotation barriers around C1–C2 bond (see atom
numeration in Figure 3) for two found stable conformers are 17.7 and 18.1 kJ/mol (see Supporting
Information). However, rotation around C1–Cipso-Ar and C2–Cipso-Ar bonds demands more energy: barriers
between conformers are about 80 and 60 kJ/mol respectively. A small difference in the energy of the
correspondent conformers (12 kJ/mol) and high rotation barriers correspond to the experimentally
observed situation close to equal ratio of the intensities of NMR signals at low temperature. Thus, the
most probably the atropoisomerism for sterically hindered oximes 2ꢀ4 takes place due to the rotation
around C1–Cipso-Ar bond.
Based on analysis of reaction products of CHal3ꢀnitroethylenes 1aꢀc with arenes, one may put the
following suggestions on the influence of substituents in aromatic ring on conformations of oximes 2ꢀ4.
The formation of atropoisomers is not observed for diphenyloximes 2a, 3a, 4a and other oximes, having
no orthoꢀsubstituents in aryl ring, due to free rotation. Substituent in orthoꢀposition of aromatic ring at
carbon C2 hampers rotation that leads to the formation of two inhibited conformational forms, as for paraꢀ
xylyl substituted oximes 2c, 3b, 4b. The same is observed for oximes obtained in the reactions with
toluene (2b, entry 6, Table 1), orthoꢀ and metaꢀxylenes (2d, entry 8, Table 1 and 2e, entry 9, Table 1),
pseudocumene (2g, entry 11, Table 1), fluorobenzene (2i, entry 13, Table 1), anisole (2j, entry 16, Table
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1). For instance, there are 9 isomers of oximes 2b, obtained from 1a and toluene (entry 6, Table 1); this
amount is higher than expected number of regioisomers. On the other hand, oximes having two substituent
in orthoꢀpositions of aryl rings have only one blocked conformation. There are no atropoisomers for 2,4,6ꢀ
trimethylphenyl oximes (2f, entry 11, Table 1; 3c, entry 5, Table 2) and tetramethylphenyl oximes (2h,
entry 12, Table 1; 3d1, 3d2, entry 6, Table 2), at least at room temperature.
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It should be noted, that oxime 3b exists in only one conformation in solid state according to Xꢀray
data (see SI), in solution it gives two atropoisomers. Apart from that, we were able to crystallize one
conformer for oximes 2e and 2i (Figure 2), which exist as atropoisomers in solution.
Study on reaction mechanism.
Then a special study on reaction mechanism was undertaken. First, we carried out DFT calculations
of electronic features and reactivity of monoꢀ (A) and diꢀ (A′) protonated (on the nitro group) forms of
CHal3ꢀnitroethylenes 1aꢀc (Table 5). Positive charge distribution, the contribution of the atomic orbitals
into the molecular orbital, global electrophilicity indices (ω10), and ꢀG298 of protonation reactions 1 →
Aaꢀc → A′aꢀc were calculated.
According to the data obtained, Gibbs free energies for the first protonation 1aꢀc → Aaꢀc have
negative values ꢀ19 ꢀ ꢀ32 kJ/mol. These reactions are favorable. Contrary to that, ꢀG298 values for the
second protonation (Aaꢀc → A′aꢀc) are rather high 64 ꢀ 105 kJ/mol. The formation of the diprotonated
forms A′aꢀc of these particular nitroethylenes 1aꢀc bearing acceptor CHal3ꢀgroup is very unlikely, despite
diprotonated species were found for other nitroalkenes and nitrosterenes in superacids.4,5 Thus, the most
probably the initial reactive species at the transformations of CHal3ꢀnitroethylenes 1aꢀc in TfOH are
monoprotonated species Aaꢀc. These cations have values of electrophilicity indices ω 6.1ꢀ7.1 eV (Table
5). Carbons С1 and С2 bear a small negative charge (ꢀ0.05ꢀ ꢀ0.12 e), but atom C2 gives a substantial
contribution into LUMO (16ꢀ17%). One should expect that reactivity of the carbon C2 in cations Aaꢀc
may be explained by orbital factors.
Data for cations Ad and A′d derived from CH3ꢀnitroethylene 1d were also calculated for
comparison with the corresponding CHal3ꢀspecies (Table 5). Cations Ad and A′d possess much less
values of indices ω. It is important to note that protonation of 1d is more thermodynamically favorable
then reactions of species Aaꢀc, but diprotonation of 1d is thermodynamically unfavorable (see ꢀG298 of
reactions 1 → Ad → A′d in Table 5). Consequently, the formation of diprotonated forms of nitroalkenes,
bearing alkyl or CHal3 groups, even in superacids, is very unlikely, in general.
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Table 5. Selected electronic characteristics of CHal3ꢀnitroethylenes 1aꢀc and CH3ꢀnitroethylene 1d and
derived from them monoprotonated A and diprotoneted A′ species, ꢀG298 of protonation reactions (the
computational method DFT M06/6ꢀ311+G(2d,2p), PCM, solvent – water).
c
c
Species
EHOMO
,
ELUMO
,
ω,a
eV
3.6
q(C1),b q(C2),b k(C1)LUMO
,
k(C2)LUMO
,
ꢀG298,d
eV
eV
e
e
%
%
kJ/mol
–8.98
–3.53
–0.04
–0.22
6
18
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1a
Aa
A′a
–10.27 –5.30
–11.29 –7.04
6.1
9.9
–0.05
–0.04
–0.12
0.03
1
1
16
20
ꢀ19
105
–8.72
–8.98
–9.36
–3.48
–5.15
–6.75
3.5
6.5
–0.05
–0.07
–0.03
–0.19
–0.09
0.04
5
7
1
15
16
21
1b
ꢀ27
95
Ab
12.4
A′b
3
–7.97
–3.50
3.7
–0.05
–0.21
5
17
Br3C
1
2
NO2
1c
–8.19
–8.59
–5.10
–6.54
7.1
–0.07
–0.02
–0.11
0.01
1
1
17
22
ꢀ32
83
Ac
13.9
A′c
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ꢀ8.25
ꢀ9.27
ꢀ2.98
ꢀ4.71
3.0
5.4
ꢀ0.11
ꢀ0.10
ꢀ0.07
0.05
2
20
ꢀ
H3C
1
4
5
6
7
8
9
2
NO2
1d
3
0.4
19.7
ꢀ52
H3C
1
2
10
11
12
13
14
15
16
17
18
19
NO2H
Ad
3
ꢀ10.5
ꢀ6.36
8.6
ꢀ0.03
0.19
6.4
30.1
64
H3C
1
2+
2
NO2H2
A′d
aGlobal electrophilicity index ω = (EHOMO + ELUMO) 2/8(ELUMO ꢀ EHOMO).
bNatural charges.
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cContribution of atomic orbital into the molecular orbital.
dGibbs energies ꢀG298 of the following protonation reactions 1aꢀc + H3O+→ Aaꢀc + H2O,
and Aaꢀc + H3O+→ A′aꢀc + H2O.
Then, NMR spectra of protonated forms Aaꢀc were registered. The samples were prepared by
dissolving of CHal3ꢀnitroethylenes 1aꢀc in TfOH directly in NMR tubes at room temperature. H, 13C, 19F
1
NMR data of initial compounds 1aꢀc (in CDCl3) and the corresponding cations Aaꢀc (in TfOH) are
presented in Table 6 (see spectra in Supporting Information). Signal of proton bonded to the nitro group
1
was not detected in H NMR spectra due to the fast proton exchange in superacidic medium. Signals of
1
13
species Aaꢀc in H, C NMR spectra undergo a downfield shift in comparison with the same signals in
spectra of their neutral precursors 1aꢀc. Thus, signals of H1 and H2 in Aaꢀc are deshielded on ꢁδ 0.13–
1
13
0.31 ppm in H NMR spectra (see Table 6). In C NMR spectra the biggest deshielding is observed for
carbon C2, ꢁδ 4.3–5.1 ppm. This reveals that a large part of positive charge is localized on this carbon and
it is a reactive electrophilic center.
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Table 6. H, 13C, 19F NMR data for CHal3ꢀnitroethylenes 1aꢀc and their protonated forms AaꢀAc
respectively.
Compound
or cation
Solvent
for NMR,
r.t.
1H NMR
13C NMR
C2, ppm
H1, ppm (J,
H2, ppm (J,
C1, ppm
C3, ppm
Hz)
Hz)
9
CDCl3
7.57 d.q (J
13.4, 2.0 Hz)
7.10 d.q (J
13.0 6.4 Hz)
145.5 q (JC–F 126.1 q (JC–
3.6 Hz) F 37.1 Hz)
121.2 q
(JC–F
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270.9 Hz)
1a a
TfOH b
7.70 d.q (J
13.6, 1.7 Hz)
7.38 d.q (J
12.5, 6.3 Hz)
146.2 q (J 7.0 130.4 q (J
122.3 q (J
268.7 Hz)
Hz)
37.8 Hz)
Aa a
ꢁδ c
CDCl3
0.13
0.28
0.7
4.3
1.1
88.6
7.57 d (J 12.7 7.46 d (J 12.7
Hz) Hz)
140.3
140.8
1b
TfOH b
7.87 d (J 12.7 7.75 d (J 12.7
140.5
145.5
88.7
Hz)
Hz)
Ab
ꢁδ c
CDCl3
0.30
0.29
0.3
4.7
0.1
20.2
3
7.77 d (J 12.5 7.37 d (J 12.5
Hz) Hz)
139.8
144.2
Br3C
1
2
NO2
1c
TfOH b
ꢁδ c
8.08 d (J 12.5 7.68 d (J 12.5
139.8
0
149.3
5.1
18.5
1.7
Hz)
Hz)
Ac
0.31
0.31
а 19F NMR (376 МHz), δ, ppm: –63.92 s (1a); –66.78 s (Aa).
b CH2Cl2 was used as internal standard.
c ꢁδ – difference of chemical shifts between cations Aaꢀc and initial alkenes 1aꢀc.
Cations Aaꢀc are stable in TfOH at room temperature during several hours, but they are slowly
converted into other cationic species according to NMR monitoring. Species Aaꢀc give other cations in
24 h in TfOH. After hydrolysis of superacidic solutions of these species no products which are soluble in
organic solvents were isolated. These species afforded only undetectable water soluble compounds. A
carefull examination of NMR spectra of these unknown cations showed that they have two new signals in
19F NMR spectra in the range of δ ꢀ73.8 – ꢀ74.5 ppm, that may correspond to triflate group coming from
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1
TfOH (see spectra in Supporting Information). In H NMR spectra, signals at δ ~12.2 ppm the most
probably belong to the proton bonded to nitrogen of oxime group (see below spectrum of Nꢀprotonated
form of oxime E1 in Figure 4). This set of NMR signals points out that the most likely the formation of
protonated form of bisꢀtriflate structure IVaꢀc occures according to the mechanism shown in Scheme 2.
Cations Aaꢀc interact with triflate anion and afford compounds Iaꢀc. Protonation of Iaꢀc gives species IIaꢀ
c, which form bisꢀtriflates IIIaꢀc. The consequent dehydration and protonation leads finally to cations
IVaꢀc. Selected 1H, 13C, 19F NMR data for cations IVa,b are presented in Scheme 3 (see full spectra data
in experimental part and Supporting Information). CBr3ꢀcation IVc is also formed in accord with NMR
data, but it is less stable and transformed in some secondary products. Aqueous work up of superacidic
solutions of cations IVaꢀc may give the corresponding αꢀhydroxy hydroxamic acids, which may be very
good soluble in water and were not isolated, as it was mentioned above. We also checked reactions of
species IVaꢀc with benzene. However, no formation of oximes 2a, 3a, 4a occurred, therefore, cations
IVaꢀc do not lie on the way of formation oximes 2ꢀ4 from compounds 1aꢀc.
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H+ (TfOH)
Hal3C
Hal3C
Hal3C
TfO
Hal3C
H+
TfO-
N
N
N
OH
OH
OH
H
N
O
Aa-c
1a-c
Ia-c
O
O
O
O
Hal3C
Hal3C
TfO
Hal3C
OTf
N
Hal3C
TfO
N OH
H+
TfO-
-H2O
TfO
N
OH
N
TfO
OH
OH
OTf
IVa-c
HO
HO
HO
IIIa-c
IIa-c
Hal = F (a), Cl (b), Br (c)
δ
C2 74.7
δ
C2 84.2
H2 6.22
H
δH 12.25
δH 12.22
δ
H2 6.24
δ
H
F3C
H
N OH
Cl3C
H
N
OH
δ
C1 162.6
δ
C1 163.9
F3CO2SO
OSO2CF3
F3CO2SO
OSO2CF3
δF -73.8; - 74.5
δF -74.0; - 74.2
IVa
IVb
Scheme 3. Transformations of CHal3ꢀnitroethylenes 1aꢀc into cations IVaꢀc in TfOH for 24 h. Selected
1H, 13C, 19F NMR data for cations IVa,b (chemical shifts in ppm).
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Taking into account the data obtained (vide supra) and literature data on reaction mechanisms of
transformations of nitroalkenes in superacids,4,5 one may propose the following mechanism for the
reaction of CHal3ꢀnitroethylenes 1aꢀc with arenes in TfOH (Scheme 4). Reactions of cations Aaꢀc with
arenes through consequent formation of intermediate species B, C, D, E with final hydrolysis of
superacidic solutions afforded the target oximes 2ꢀ4.
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H+ (TfOH)
Hal3C
Hal3C
Hal3C
Hal3C
H+
ArH
-H+
N
N
Ar
B
N
OH
O
OH
OH
OH
N O
Aa-c
1a-c
O
O
O
H
Hal3C
Hal3C
Ar
Hal3C
Ar
N
Hal3C
N OH
Hal3C
Ar
N OH
Ar
H2O
-H+
ArH
-H+
H+
-H2O
Ar
N
OH
N
Ar
OH
Ar
Ar
HO
HO
D
HO
2,3,4
C
E
Hal = F (a), Cl (b), Br (c)
Scheme 4. Mechanism of reaction of CHal3ꢀnitroethylenes 1aꢀc with arenes in TfOH.
To have additional proof on this reaction mechanism we conducted a special NMR experiment to
catch some intermediate species. H and 13C NMR spectra of mixture of 1b and benzene in TfOH at low
temperature ꢀ38°C were registered. The main signals in H and 13C NMR belong to cation C1, as product
1
1
of reaction of 1b with one benzene molecule (Figure 3, see the mechanism in Scheme 4). The minor
signals correspond to cation E1, which is Nꢀprotonated form of oxime 2b. NꢀPrtonation was confermed by
HSQC H–15N data (see Supporting Information). Upon increasing time or reaction temperature, species
1
C1 is completely converted into E1 one (see Figure 4). The latter was also independently generated by
dissolving of oxime 2b in TfOH. That also means that dehydration of species D, leading to cations E,
proceeds in the superacidic solution, rather than upon hydrolysis of it. These NMR data unambigously
reveal that intermediate cations C and E really lie on the way of transformation of CHal3ꢀnitroethylenes
1aꢀc into the corresponding oximes 2ꢀ4 (Scheme 4).
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TfOH
C6H6
OH
5
6
Cl3C
N OH
7
8
9
H
Ph
H
5.42 ppm
C1
8.73 ppm
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19
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23
24
25
5.88 ppm
Cl3C HN OH
H
Ph
E1
Ph
ratio C1 : E1 1 : 0.2
Figure 3. 1H NMR spectrum of mixture of cations C1 and E1 generated at the reaction of 1b and benzene
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in NMR tube in TfOH at –38°С in 30 min (400 MHz, benzene as internal standard).
TfOH
Cl3C HN OH
H
Ph
2Ph
C6H6
Ph
H2
E1
CH2Cl2
NH+
1
Figure 4. H NMR spectrum of cation E1 generated at the reaction of 1b and benzene in TfOH at room
temperature (400 MHz, CH2Cl2 as internal standard).
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Apart from NMR studies, we tried to catch cations C by quenching superacidic reaction solution
with various nucleophilic media. Thus, reaction of CF3ꢀnitroethylene 1a with paraꢀxylene in FSO3Hꢀ
CH2Cl2 at ꢀ80°С in 1h followed by quenching with concentrated solution of hydrochloric acid at ꢀ30°С
resulted in the formation of compound 5a (Scheme 5, see Xꢀray structure in SI). The latter is obtained as
a result of interaction of intermediate cation C2 with HCl, as a nucleophile.
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CH3
F3C
F3C
H3C
F3C
HClaq.(–30°C)
–H2O
H3C
FSO3H,CH2Cl2
–80°C, 1h
OH
N
OH
N
HO
NO2
HO
–H+
CH3
1a
C2
CH3
CH3
F3C
N OH
Cl
H3C
CH3
5a,36%
Scheme 5. Reaction of 1a with paraꢀxylene in FSO3HꢀCH2Cl2 (ꢀ80°С, 1h) followed by quenching
with concentrated hydrochloric acid at ꢀ30°С leading to compound 5a.
In the same way, work up of superacidic solution of cation C1 with MeOH (–80°С) afforded
compound 5b as a result of deprotonation of C1 (Scheme 6). However, the use of other systems, such as,
HBraq.,conc. (–40°С), CH3ONaꢀCH3OH (–80°С), H2O (0°С), to quench superacidic solutions of cation C1
gave complex mixtures of unidentified compounds.
Cl3C
Cl3C
Ph
Cl3C
MeOH (–80°C)
– H+
TfOH, CH2Cl2
–40°C, 1h
Ph
N
NO2
NO2
OH
1b
HO
5b, 30%
C1
Scheme 6. Reaction of 1b with benzene in TfOHꢀCH2Cl2 (ꢀ40°С, 1h) followed by quenching with MeOH
leading to compound 5b.
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Synthesis of organic compounds from oximes 2-4.
The presence of CHal3 group in the structure of oximes 2ꢀ4 makes them very flexible and promising
synthons for further transformations. We performed synthesis of 5ꢀhalogenoꢀ3,4ꢀdiarylisoxazoles 6aꢀe
from CCl3ꢀ(3a,b,f) and CBr3ꢀ(4a) oximes with DBU as a base under the conditions of microwave or
thermal activation (Table 7). Under microwave irradiation for short reaction time, an intermediate
dihalageno derivative 6e was obtained (entry 7, Table 7). Attempt of hydrolysis of oxime 3a with H3PO4
to obtain the corresponding ketone according to the literature procedure11 resulted in isoxazole 6a (entry 2,
Table 7), rather than expected ketone.
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Table 7. Synthesis of isoxazoles 6aꢀe from CCl3ꢀ(3a,b,f) and CBr3ꢀ(4a) oximes.
Ar
Ar
Hal
Hal
Ar
Ar
Hal
Hal3C
Ar
N OH
Ar
Hal3C
Ar
N O
Ar
DBU
– DBUH+
DBU
– Hal –
– DBUH+
N
N
– Hal –
O
O
3a,b,f, 4a
6a-e
Hal = Cl, Br
Entry
Initial oxime
Reaction conditionsa
DMF, DBU, MW, 100°С, 5 min
Reaction product, yield %
1
Z-3a
6a, 59%
6a, 55%
6a, 51%
2
3
4
Z-3a
Z-3a
H3PO4 (2.5 M), EtOH, 95°С, 60 h
DMF, DBU, 100°С, 1 h
DMF, DBU, MW, 100°С, 1 h
Z-3b
Z-3f
6b, 53%
6c, 55%
5
DMF, DBU, MW, 100°С, 10 min
6
7
DMF, DBU, 100°С, 1 h
Z-4a
Z-4a
6d, 67%
6e, 37%
DMF, DBU, MW, 100°С, 5 min
a MW – microwave irradiation
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Beckmann rearrangement of oximes 2a, 3a, 4a under the action of PCl5 was done using literature
method12 (Scheme 7). It was found that initial products in this reaction were imidoyl chlorides E-,Zꢀ7aꢀc,
which are stable to hydrolysis at the reaction work up. Then, under separation of isomers E-,Zꢀ7aꢀc by
TLC on silicagel, they were transformed into the corresponding benzamides 8aꢀc (see Xꢀray structures in
Supporting Information). It should be noted that Beckmann rearrangement of 2a, 3a, 4a did not go upon
longer reaction time in TfOH. Increasing of the reaction temperature up to 60ꢀ80°C resulted in the
formation of complex mixtures of reaction products.
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Cl
Hal3C
Ph
N OH
Ph
Hal3C
Ph
N Cl
Ph
O
PCl5, C6H6
silica gel
CHal3
N
NH
– HCl
– POCl3
Ph
Ph
CHal3
Ph
8a-c, 46-47 %
Ph
2a, 3a, 4a
E-,Z-7a-c, 94-96%
X = F (2a, 7a, 8a), Cl (3a, 7b, 8b), Br (4a, 7c, 8c)
Scheme 7. Beckmann rearrangement of oximes 2a, 3a, 4a leading to compounds E-,Zꢀ7aꢀc and then to
benzamides 8aꢀc.
CONCLUSIONS
Reactions of 3,3,3ꢀtrihalogenoꢀ1ꢀnitropropenes with arenes in TfOH leading to the formation of
3,3,3ꢀtrihalogenoꢀ1,2ꢀdiarylpropanꢀ1ꢀone oximes have been studied. These CHal3ꢀoximes bearing orthoꢀ
substituents in aryl ring may exist as atropoisomers in solutions at room temperature. Cationic
intermediates of this reaction have been investigated by means of NMR and DFT calculations, that sheds
light on the proposed reaction mechanism. It has been shown that CHal3ꢀoximes are promising precursors
for synthesis of isoxazole derivatives and benzamides, as products of Beckman rearrangement.
Experimental Section
The NMR spectra of solutions of compounds in CDCl3 or DMSOꢀd6 were recorded at 400, 376 and
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100 MHz for H, F and C NMR spectra respectively at 25 °C. The solvent residual signals CDCl3 (δ
7.26 ppm) or DMSOꢀd6 (δ 2.50 ppm) for 1H NMR spectra and the carbon signal of CDCl3 (δ 77.0 ppm) or
DMSOꢀD6 (δ 39.52 ppm) for 13C NMR spectra were used as references. 19F NMR spectra were indirectly
referred to the signal of CFCl3 (δ 0.0 ppm). NMR spectra in TfOH were referenced to the signal of CH2Cl2
1
or benzene added as internal standard: δ 5.30 or 7.48 ppm for H NMR spectra, and δ 53.52 or 129.5 ppm
for 13C NMR spectra respectively. IR spectra of compounds were taken in KBr. HRMS was carried out in
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ESI mode. The preparative reactions were monitored by thinꢀlayer chromatography carried out on silica
gel plates using UV light for detection. Preparative TLC was performed on silica gel 5ꢀ40 ꢂm. Reactions
under microwave activation were carried out at a special machine in sealed reaction vessels, the reaction
temperature was monitored by internal probe type (CEM Discovery SP), and the temperature maintained
in each experiment as indicated in Table 7.
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Dynamic NMR study. Study of atropoisomeric equilibrium of compounds 2c, 3b, 4b was carried
out by the registration of NMR spectra in DMSOꢀD6 at different temperatures for 2c, 3b from 25°C to
120°C with step 5°C to 90°C then with step 10°C to 120°C, and for 4b in from 25°C to 120°C with step
5°C. Line shape analysis was performed in the DNMR module of the TopSpin version 3.2. Based on the
found reaction rate constants at each temperature, values of activation energies were found using
Arrhenius plot.13
Xꢀray diffraction study. A suitable crystal was selected and studied on the diffractometer. The
crystal was kept at 100(2) K during data collection. Using Olex214 the structure was solved with the
ShelXS15 structure solution program using Direct Methods and refined with the ShelXL refinement
package using Least Squares minimization. CCDC 1844189 – (2a), CCDC 1844194 – (2e), CCDC
1844192– (2h), CCDC 1552333– (9a), CCDC 1844196 – (2i), CCDC 1844185 – (3a), CCDC 1844191
– (3b), CCDC 1844193 – (3d1, 3d2), CCDC 1844198 – (3e1, 3e2), CCDC 1844190 – (4a), CCDC
1844197 – (5a), CCDC 1845172 – (8a), CCDC 1845173 – (8b), CCDC 1845174 – (8c) contain the
supplementary crystallographic data, which can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.htmL or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.)
+
44ꢀ1223ꢀ336ꢀ033; Eꢀmail:
deposit@ccdc.cam.ac.uk.
DFT calculations. All computations were carried out at the DFT/HF hybrid level of theory using
hybrid exchange functional M06 by using GAUSSIAN 2009 program packages.16 The geometries
optimization were performed using the M06/6ꢀ311+G(2d,2p) basis set (standard 6ꢀ311 basis set added
with polarization (d, p) and diffuse functions). Optimizations were performed on all degrees of freedom
and solventꢀphase optimized structures were verified as true minima with no imaginary frequencies. The
Hessian matrix was calculated analytically for the optimized structures in order to prove the location of
correct minima and to estimate the thermodynamic parameters. Solventꢀphase calculations used the
Polarizable Continuum Model (PCM).
Initial 3,3,3ꢀtrihalogenoꢀ1ꢀnitropropenes 1aꢀc were obtained as reported previously.[17ꢀ19]
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(E)ꢀ3,3,3ꢀTrifluoroꢀ1ꢀnitropropꢀ1ꢀene (1a).17 NMR 1H, δ, ppm: 7.10 dq (1H, J 13.0, 6.4 Hz), 7.57
13
dq (1H, J 13.4, 2.0 Hz). NMR C, δ, m.d: 121.2 q (CF3, J 270.9 Hz), 126.1 q (C2, J 37.1 Hz), 145.5 q
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(C1, J 3.6 Hz). NMR 19F, δ, ppm: ꢀ63.92 s (CF3).
E)ꢀ3,3,3ꢀTrichloroꢀ1ꢀnitropropꢀ1ꢀene (1b).18 NMR 1H, δ, ppm: 7.46 d (1H, J 12.7 Hz), 7.57 d (1H,
J 12.7 Hz). NMR 13C, δ, ppm: 88.6 (CCl3), 140.3 (C2), 140.8 (C1).
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(E)ꢀ3,3,3ꢀTribromoꢀ1ꢀnitropropꢀ1ꢀene (1c).19 NMR H, δ, ppm: 7.37 d (1H, J 12.5 Hz), 7.77 d
(1H, J 12.5 Hz). NMR 13C, δ, ppm: 20.2 (CBr3), 139.8 (C1), 144.2 (C2).
General procedure for the synthesis of oximes 2ꢀ4 from 3,3,3ꢀtrihalogenoꢀ1ꢀnitropropꢀ1ꢀenes
1aꢀc in TfOH. 3,3,3ꢀTrihalogenꢀ1ꢀnitropropene (1) (0.31 mmol) was added to a mixture of benzene (0.4
mL, 4.49 mmol) or other arene (0.62 mmol, in this case cosolvent was CH2Cl2, 0.4 mL) and TfOH (0.4
mL). The mixture was stirred at room temperature for 1 h, then poured into water (40 mL), and extracted
with CH2Cl2 (3×20 mL). The combined organic phases were washed with saturated aqueous solution of
NaHCO3 (20 mL) and twice with water (20 mL), then dried with Na2SO4. Solvent was evaporated under
the reduced pressure. In some cases, reaction products were additionally purified by preparative TLC on
silica gel with eluation by petroleum ether–ethyl acetate mixtures.
In the same way these reactions were carried out with 1 (0.2 mmol), AlCl3 or AlBr3 (1 mmol, 5
equiv.) in benzene (5mL) at room temperature for 0.5 h.
Procedure for large scale reaction of 1a with benzene in TfOH leading to oxime 2a. Compound
1a (500 mg, 1.55 mmol) was gradually added to a mixture of benzene (1.5 mL, 0.017 mol) and TfOH (2
mL). The mixture was stirred at room temperature for 1 h, then poured into water (50 mL), and extracted
with CH2Cl2 (3×30 mL). The combined organic phases were washed with saturated aqueous solution of
NaHCO3 (30 mL) and twice with water (30 mL), then dried with Na2SO4. After evaporation of solvent
under the reduced pressure, the reaction product was obtained in the yield of 960 mg (97%).
Procedure for the synthesis of imidoyl chloride 5a. 3,3,3ꢀTrifluoroꢀ1ꢀnitropropene (1a) (30 mg,
0.2 mmol) was added to a mixture of fluorosulfonic acid FSO3H (0.7 mL), CH2Cl2 (0.8 mL) and pꢀxylene
(46 mg, 0.426 mmol) at –80°C. After stirring at –80°C for 1 h, the reaction mixture was poured into
concentrated hydrochloric acid (15 mL) cooled at –30°C and left to heat to room temperature. After
extraction with CH2Cl2 (3×30 ml), the combined organic phases were washed with saturated aqueous
solution of NaHCO3 (20 mL) and twice with water (20 mL), dried with Na2SO4. After evaporation of
organic solvents under the reduced pressure, the reaction product (5a) was obtained without additional
purification.
Procedure for the synthesis of propane 5b. 3,3,3ꢀTrichloroꢀ1ꢀnitropropene (1b) (30 mg, 0.16
mmol) was added to a mixture of TfOH (0.7 mL), CH2Cl2 (0.3 mL) and benzene (0.3 mL) at –40°C . After
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stirring at –40°C for 1 h, the reaction mixture was poured into methanol (15 mL) cooled at –80°C and left
to heat to room temperature. After extraction with CH2Cl2 (3×30 ml), the combined organic phases were
washed with saturated aqueous solution of NaHCO3 (20 mL) and twice with water (20 mL), dried with
Na2SO4. After evaporation of organic solvents under the reduced pressure, the reaction product (5b) was
obtained without additional purification.
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General procedure for the synthesis of isoxazoles 6aꢀс.
A solution of oxime (3a,b,f, or 4a) (0.3 mmol) and DBU (0.6 mmol, 2 eqiuv.) in DMF (1 mL) was
stirred in an ampoule with a polymer lid under MW irradiation at 100°C for the time as indicated in Table
7. The reaction mixture was poured into water (40 ml) and extracted with CH2Cl2 (3×20 ml). Combined
organic phases were dried with Na2SO4. Solvent was evaporated under the reduced pressure. The reaction
product was purified by preparative TLC on silica gel with eluation by petroleum ether–ethyl acetate
mixtures. In the same way this reaction was conducted under usual thermal activation by heating (see
Table 7).
General procedure for the synthesis of imidoyl chlorides 7aꢀс and benzamides 8aꢀc.
PCl5 was portion wise added to a mixture of oxime (2a, 3a, or 4a) (0.1 mmol) in benzene (1 mL).
After stirring at room temperature for 24 h, the reaction mixture was poured into water (30 mL) and
extracted with CH2Cl2 (3×20 mL). Combined organic phases were dried with Na2SO4. After evaporation
of solvent the under reduced pressure, the reaction products, mixtures of E-/Z-isomers 7aꢀс, were obtained
without additional purification. Being subjected to preparative TLC on silica gel with eluation by
petroleum ether–ethyl acetate mixtures, compounds 7aꢀc were transformed into benzamides 8aꢀc.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀdiphenylpropanꢀ1ꢀone oxime (2a). Obtained from 1a (100 mg, 0.31
mmol) and benzene (350 mg, 4.49 mmol). Yield 193 mg (97%). Solid, mp 152ꢀ153°C. Structure
1
confirmed by single crystal Xꢀray analysis (see Supporting Information). Н NMR, δ, ppm: 4.54 q (1H, J
13
9.1 Hz), 7.18ꢀ7.20 m (2H), 7.34ꢀ7.38 m (6H), 7.42ꢀ7.44 m (2H), 8.39 s (1H, OH). C NMR, δ, ppm: 55.8
q (C2, J 28.1 Hz), 125.03 q (CF3, J 280.5 Hz), 127.9, 128.4, 128.9, 129.0, 129.4, 130.0, 131.3, 132.5,
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153.3. F NMR, δ, ppm: –65.52 s (CF3). IR (KBr, cmꢀ1): 3306 (OH), 1496 (C=N), 993 (N–O). HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H12F3NONa 302.0763; Found 302.0780.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(methylphenyl)propanꢀ1ꢀones oximes (2b, mixture of regioꢀ and
atropoisomers). Obtained from 1a (30 mg, 0.21 mmol) and toluene (39mg, 0.43 mmol). Yield 55 mg
1
(84%). Solid, mp 114ꢀ116°C. Main Н NMR signals of the mixture of isomers, δ, ppm: CH3 singlets
(2.26ꢀ2.39), H quartets (4.28ꢀ4.34, 4.47ꢀ4.55, 4.67ꢀ4.74, 4.86ꢀ4.93), H (5.41 s, 6.64ꢀ6.65 m, 6.94ꢀ7.33 m,
7.61 s), H singlets (8.66ꢀ8.77, H, OH). Main 13C NMR signals of the mixture of isomers, δ, ppm: Me
(21.2, 21.3, 21.47, 21.51, 21.54), C quartets (54.9ꢀ55.8), 124.9, 125.7, 126.50, 126.55, 126.59, 126.72,
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127.8, 127.9, 128.29, 128.31, 128.33, 129.5, 129.57, 129.62, 129.8, 129.9, 130.1, 130.2, 130.9, 153.2,
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153.4, 154.0. Main F NMR signals of the mixture of isomers, δ, ppm: CF3 (–65.65, –65.64, –65.60, –
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65.59, –65.53, –65.43, –65.40, –65.33, –60.09, –65.04, –64.86). HRMS (ESIꢀTOF) m/z: [M + Na]+ (for
mixture of isomers) Calcd for C17H16F3NONa 330.1077; Found 330.1076.
(Z)ꢀ1,2ꢀBis(2,5ꢀdimethylphenyl)ꢀ3,3,3ꢀtrifluoropropanꢀ1ꢀone oxime (2c). Obtained from 1a (30
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mg, 0.21 mmol) and p-xylene (45 mg, 0.43 mmol). Yield 67 mg (94%). Solid, mp 148ꢀ149°C. H NMR,
atropoisomer 1 (signals from the spectrum of the mixture of atropoisomers), δ, ppm: 2.11 s (3H, CH3),
1
2.14 s (3H, CH3), 2.15 s (3H, CH3), 2.31 s (3H, CH3), 4.63 q (1H, J 9.2 Hz), 6.31 s (1H). H NMR,
atropoisomer 2 (signals from the spectrum of the mixture of atropoisomers), δ, ppm: 1.89 s (3H), 2.16 s
(3H, CH3), 2.29 s (3H, CH3), 2.30 s (3H, CH3), 4.81 q (1H, J 9.2 Hz), 6.76 s (1H). For the mixture of
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atropoisomers H NMR, δ, ppm: 6.97ꢀ7.12 m (8H), 7.37 d (2H, J 17.5 Hz), 8.08 m (2H+1H, OH). 13C
NMR, atropoisomer 1 (signals from the spectrum of the mixture of atropoisomers), δ, ppm: 18.7, 21.0,
21.0, 21.2, 50.6 q (C2, J 27.9 Hz), 125.3 q (CF3, J 280.9 Hz). 13C NMR, atropoisomer 2 (signals from the
spectrum of the mixture of isomers), δ, ppm: 19.3, 19.4, 19.4, 21.1, 51.1 q (C2, J 28.0 Hz), 125.4 q (CF3, J
13
280.8 Hz). For the mixture of isomers C NMR, δ, ppm: 127.0, 128.9, 129.1, 129.5, 129.6, 129.9, 130.0,
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130.0, 130.1, 130.4, 130.6, 132.2, 132.7, 132.8, 133.5, 134.4, 134.6, 135.1, 135.6, 136.0, 154.1, 154.5. F
NMR δ, ppm: –64.80 s (CF3, atropoisomer 1), –65.07 s (CF3, atropoisomer 2). IR (KBr, cmꢀ1) (for mixture
of atropoisomers): 3325 (OH), 1620 (C=N), 994 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H20F3NONa 358.1389; Found 358.1395.
(Z)ꢀ1,2ꢀBis(dimethylphenyl)ꢀ3,3,3ꢀtrifluoropropanꢀ1ꢀones oximes (2d, mixture of regioꢀ and
atropoisomers). Obtained from 1a (30 mg, 0.21 mmol) and o-xylene (45 mg, 0.43 mmol). Yield 55 mg
1
(87%). Solid, mp 137ꢀ138°C. Main H NMR signals of the mixture of isomers, δ, ppm: CH3 singlets
(1.90, 2.15, 2.21, 2.22, 2.24, 2.25, 2.26, 2.28, 2.29, 2.30, 2.31), 4.26 q (H, J 9.3 Hz), H quartets (4.38ꢀ
4.51), 4.79 q (H, J 9.1 Hz), H quartets (4.96ꢀ5.03), H (5.38 s, 6.90ꢀ7.19 m, 7.47ꢀ7.54 m, 6.36 d J 7.6 Hz,
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6.49 d J 7.6 Hz), 8.50ꢀ8.58 (H, OH, singlets). Main C NMR signals of the mixture of isomers, δ, ppm:
CH3 singlets (16.3, 17.0, 19.57, 19.84, 19.88, 19.9, 20.44, 20.46, 21.30, 21.33), C2 quartets (55.0ꢀ56.4),
CF3 quartets (120.9ꢀ129.2), 124.43, 124.47, 125.19, 125.37, 125.53, 125.65, 125.75, 126.2, 126.52,
126.57, 127.38, 127.47, 127.7, 128.08, 128.22, 128.26, 128.76, 128.86, 128.9, 129.18, 129.21, 129.31,
129.46, 129.6, 129.9, 130.08, 130.16, 130.52, 130.61, 130.65, 131.13, 131.26, 131.39, 133.3, 139.4,
133.8, 134.9, 135.9, 136.15, 136.3, 136.6, 136.64, 136.9, 137.12, 137.17, 137.33, 137.39, 137.58, 138.0,
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138.07, 153.3, 154.6. Main F NMR signals of the mixture of isomers, δ, ppm: –65.60 s (CF3), –65.50 s
(CF3), –65.00 s (CF3), –64.84 s (CF3). HRMS (ESIꢀTOF) m/z: [M + H]+ (for mixture of isomers) Calcd
for C19H21F3NO 336.1570; Found 336.1577.
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(Z)ꢀ1,2ꢀBis(dimethylphenyl)ꢀ3,3,3ꢀtrifluoropropanꢀ1ꢀones oximes (2e, mixture of regioꢀ and
atropoisomers). Obtained from 1a (30 mg, 0.21 mmol) and mꢀxylene (45 mg, 0.43 mmol). Yield 60 mg
(85%). Solid, mp 136ꢀ137°C. Structure confirmed by single crystal Xꢀray analysis (see Supporting
Information). Main 1H NMR signals of the mixture of isomers, δ, ppm: CH3 s (1.62, 1.93, 1.95, 2.12, 2.14,
2.22, 2.26, 2.28, 2.30, 2.31, 2.34, 2.38), H quartets (4.61ꢀ4.71), 4.82 q (H, J 9.0 Hz), 6.44 d (H, J 7.75 Hz),
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H (6.80 s, 6.85ꢀ7.17 m, 7.47ꢀ7.52 m, 7.61ꢀ7.67 m), 8.56ꢀ8.69 singlets (H, OH). Main C NMR signals of
the mixture of isomers, δ, ppm: 19.2, 19.5, 19.6, 19.79, 19.83, 19.87, 21.16, 21.19, 21.3, 21.4, C2 quartets
(49.6ꢀ51.1), CF3 quartets (124.0ꢀ129.6), 125.3, 126.2, 126.3, 126.37, 126.44, 126.5, 126.8, 127.0, 127.1,
127.26, 127.32, 127.7, 127.9, 128.9, 129.5, 129.7, 130.0, 130.8, 131.04, 131.42, 131.57, 131.61, 131.64,
132.6, 132.9, 134.4, 135.2, 136.1, 136.7, 137.29, 137.34, 137.47, 137.61, 131.9, 138.52, 138.54, 138.63,
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138.67, 138.9, 139.0. Main F NMR signals of the mixture of isomers, δ, ppm: –65.60 s (CF3), –65.50 s
(CF3), –65.00 s (CF3), –64.84 s (CF3). HRMS (ESIꢀTOF) m/z: [M + Na]+ (for mixture of isomers) Calcd
for C19H20F3NONa 358.1389; Found 358.1401.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(2,4,6ꢀtrimethylphenyl)propanꢀ1ꢀone oxime (2f). Obtained from 1a
(30 mg, 0.21 mmol) and mesitylene (1,3,5ꢀtrimethylbenzene) (51 mg, 0.43 mmol). Yield 74 mg (96%).
Solid, mp 160ꢀ162°C. 1H NMR δ, ppm: 1.67 s (3H, CH3), 1.92 s (3H, CH3), 2.23 s (3H, CH3), 2.24 s (3H,
CH3), 2.37 s (3H, CH3), 2.61 s, 4.92 q (1H, J 10.4 Hz), 6.68 s (1H), 6.74 s (1H), 6.88 s (1H), 6.91 s (1H),
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8.12 s (1H). C NMR δ, ppm: 19.2, 19.3, 20.6 q (CH3, J 14.5 Hz), 20.9, 21.2, 21.3, 50.4 q (C2, J 28.6
Hz), 124.3, 125.9 q (CF3, J 281.5 Hz), 128.5, 128.7, 129.6, 129.9, 131.7, 134.0, 136.1, 138.3, 138.6,
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139.2, 140.1, 153.5. Main F NMR signals of the mixture of isomers, δ, ppm: –61.55 s (CF3). IR (KBr,
cmꢀ1): 3348 (OH), 1612 (C=N), 990 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C21H24F3NONa
386.1703; Found 386.1717.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(trimethylphenyl)propanꢀ1ꢀones oximes (2g, mixture of regioꢀ and
atropoisomers). Obtained from 1a (0.21 mmol) and pseudocumene (1,2,4ꢀtrimethylbenzene) (51 mg,
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0.43 mmol). Yield 70 mg (91%). Solid, mp 135ꢀ137°C. Main H NMR signals of the mixture of isomers,
δ, ppm: CH3 singlets (1.53, 1.61, 1.80, 1.88, 1.90, 2.07, 2.08, 2.10, 2.129, 2.133, 2.15, 2.168, 2.173, 2.21,
2.22, 2.23, 2.24, 2.27, 2.30), H quartets (4.56ꢀ4.64, 4.73ꢀ4.82), H (6.22 s, 6.33 s, 6.66 s, 6.76ꢀ7.04 m, 7.32ꢀ
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7.44 m), 8.33ꢀ8.47 m (H, OH, singlets). Main C NMR signals of the mixture of isomers, δ, ppm: CH3
singlets (15.8, 16.5, 16.9, 18.7, 18.9, 19.3, 19.4ꢀ19.52, 19.6, 20.1, 20.2, 20.38, 20.42, 20.92, 20.94, 21.3),
C2 quartets (49.5ꢀ51.4), CF3 quartets (121.3ꢀ129.7), 124.6, 126.35, 126.42, 126.68, 126.86, 126.93,
127.49, 127.56, 127.73, 130.3, 130.47, 130.49, 130.54, 130.8, 13.1, 131.54, 131.57, 131.6, 131.83,
131.86, 131.90, 131.94, 132.02, 132.07, 132.3, 132.6, 132.7, 132.87, 132.9, 133.0, 133.2, 133.4, 133.8,
133.9, 134.16, 134.18, 134.21, 134.25, 134.28, 134.3, 134.4, 134.56, 134.58, 134.67, 134.81, 134.89,
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134.95, 134.97, 154.2, 154.6, 154.9, 155.1. Main F NMR signals of the mixture of isomers, δ, ppm: CF3
s (ꢀ64.18, ꢀ65.15, ꢀ64.88, ꢀ64.69, ꢀ64.47, ꢀ64.44, ꢀ64.41, ꢀ64.31, ꢀ64.23). HRMS (ESIꢀTOF) m/z: [M +
Na]+ (for mixture of isomers) Calcd for C21H24F3NONa 386.1703; Found 386.1702.
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(Z)-3,3,3ꢀTrifluoroꢀ1,2ꢀbis(2,3,5,6ꢀtetramethylphenyl)propanꢀ1ꢀone oxime (2h). Obtained from
1a (30 mg, 0.21 mmol) and durene (1,2,4,5ꢀtetramethylbenzene) (57 mg, 0.43 mmol). Purification by
preparative TLC with mixture petroleum ether – ethyl acetate, 7:3. Yield 55 mg (71%). Solid, mp 232ꢀ
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234°C. Structure confirmed by single crystal Xꢀray analysis (see Supporting Information). H NMR, δ,
ppm: 1.55 s (3H), 1.77 s (3H), 2.04 s (3H), 2.14 s (3H), 2.21 s (3H), 2.26 s (3H), 2.29 s (3H), 2.52 q (3H,
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J 1.2 Hz), 5.05 q (1H, J 10.4 Hz), 6.92 s (1H), 6.94 s (1H), 8.02 s (1H). C NMR, δ, ppm: 15.9, 16.1,
16.1, 17.5 q (CH3, J 4. 6 Hz), 19.9, 20.0, 20.6, 21.6, 51.3 q (C2, J 28.2 Hz), 126.0 q (CF3, J 281.7 Hz),
127.3, 129.7, 131.8, 132.2, 132.6, 133.1, 133.8, 133.9, 134.2, 135.1, 135.6, 136.3, 155.1. 19F NMR, δ,
ppm: –61.12 s (CF3). IR (KBr, cmꢀ1): 3439 (OH), 1603 (OH), 1025 (N–O). HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C23H28F3NONa 414.2015; Found 414.2036.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(fluorophenyl)propanꢀ1ꢀones oximes (2i, mixture of regioꢀ and
atropoisomers). Obtained from 1a (30 mg, 0.21 mmol) and fluorobenzene (41 mg, 0.43 mmol). Yield 37
mg (55%). Solid, mp 128ꢀ130°C. Structure confirmed by single crystal Xꢀray analysis (see Supporting
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Information). Main H NMR signals of the mixture of isomers, δ, ppm: 4.46ꢀ4.57 m (H, quartets), 5.06 q
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(1H, J 8.86 Hz), 6.91ꢀ7.20 m (H), 7.36ꢀ8.00 m (H, OH singlets). Main C NMR signals of the mixture of
isomers, δ, ppm: 55.0 q (C2, J 28.4 Hz), C quartets(54.4ꢀ55.2), CF3 quartets (115.3ꢀ116.7), 120.1 d (C, J
16.9 Hz), 121.5, 123.5 d (C, J 3.2 Hz), 123.7, 124.2 d (C, J 3.5 Hz),124.6 d (C, J 3.7 Hz), 125.9, 126.7,
126.9, 127.0 d (C, J 1.3 Hz), 128.1 d (C, J 3.4 Hz), 128.1 d (C, J 3.4 Hz), 128.2, 129.5 d (C, J 3.6 Hz),
130.0 d (C, J 8.5 Hz), 130.2 d (C, J 8.2 Hz), 130.7, 130.8, 130.87, 130.94, 131.5 d (C, J 8.2 Hz), 131.7 d
(C, J 8.3 Hz), 131.8, 134.1 d (J 7.6 Hz), 149.1, 152.0, 152.3, 157.8, 159.8, 161.5, 162.1 d (J 18.3 Hz),
162.23 d (J 6.5 Hz), 163.5, 164.1 d (J 17.0 Hz), 164.2 d (J 7.0 Hz). Main 19F NMR signals of the mixture
of isomers, δ, ppm: CF3 (ꢀ65.81, ꢀ65.87), F (ꢀ110.59, ꢀ111.82, ꢀ112.01, ꢀ112.39, ꢀ112.47, ꢀ112.68). HRMS
(ESIꢀTOF) m/z: [M + Na]+ (for mixture of isomers) Calcd for C15H10F5NONa 338.0575; Found 338.0584.
(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(metoxyphenyl)propanꢀ1ꢀones oximes (2j, mixture of regioꢀ and
atropoisomers). Obtained from 1a (30 mg, 0.21 mmol) and anisole (methoxybenzene) (46 mg, 0.43
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mmol). Yield 45 mg (63%). Oil. Main H NMR signals of the mixture of isomers, δ, ppm: CH3 singlets
(3.66, 3.67, 3.73, 3.76, 3.79, 3.80, 3.81, 3.83), 1H quartets (4.44ꢀ4.56, 4.65ꢀ4.77), H m (6.80ꢀ6.93, 7.16ꢀ
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7.25, 7.27ꢀ7.46), H singlets (8.14ꢀ8.54, OH). Main C NMR signals of the mixture of isomers, δ, ppm:
OMe (54.8, 55.3, 55.3, 55.38, 55.43, 55.77, 55.80), 111.2, 113.5, 113.6, 113.8, 114.0, 114.3, 120.5, 121.6,
123.5, 124.3, 124.6, 125.9, 127.6, 129.0, 129.56, 129.62, 129.9, 130.70, 131.1, 131.3, 131.4, 155.9, 159.8,
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160.0, 160.2. Main 19F NMR signals of the mixture of isomers, δ, ppm: CF3 (ꢀ69.8, ꢀ65.93, ꢀ65.88, ꢀ65.87,
ꢀ65.78, ꢀ65.77). HRMS (ESIꢀTOF) m/z: [M + Na]+ (for mixture of isomers) Calcd for C17H16F3NO3Na
362.0975; Found 362.0974.
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(Z)ꢀ3,3,3ꢀTrifluoroꢀ1,2ꢀbis(3,4ꢀdimethoxyphenyl)propanꢀ1ꢀone oxime (2k). Obtained from 1a
(30 mg, 0.21 mmol) and veratrol (1,2ꢀdimethoxybenzene) (59 mg, 0.43 mmol). Purification by preparative
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TLC with mixture petroleum ether – ethyl acetate, 7:3. Yield 50 mg (59%). Solid, mp 142ꢀ144°C. H
NMR, δ, ppm: 3.77 s (3H, OMe), 3.82 s (3H, OMe), 3.86 s (3H, OMe), 3.87 s (3H, OMe), 4.47 q (1H, J
9.11 Hz), 6.78ꢀ6.84 m (4H), 6.93ꢀ6.96 m (2H), 8.69 s (1H, OH). 13C NMR, δ, ppm: 55.3 q (C2, J 28.1
Hz), 55.9 (OMe), 56.0 (2C, OMe), 56.0 (OMe), 110.8, 111.2, 111.5, 112.7, 120.9, 122.7, 123.8, 124.7,
125.1 q (CF3, J 280.5 Hz), 126.2, 128.4, 148.6, 149.2, 149.6, 149.7, 152.6. 19F NMR, δ, ppm: ꢀ65.71 s
(CF3). IR (KBr, cmꢀ1): 3392 (OH), 1643 (C=N), 986 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H20F3NO5Na 422.1186; Found 422.1191.
(Z)ꢀ3,3,3ꢀTrichloroꢀ1,2ꢀdiphenylpropanꢀ1ꢀone oxime (3a). Obtained from 1b (500 mg, 2.65
mmol) and benzene(3500 mg, 44.90 mmol). Yield 730 mg (99%). Solid, mp 158ꢀ159°C. Structure
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confirmed by single crystal Xꢀray analysis (see Supporting Information). H NMR, δ, ppm: 4.89 s (1H),
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7.18ꢀ7.20 m (2H), 7.33ꢀ7.35 m (3H), 7.38ꢀ7.40 m (3H), 7.66ꢀ7.68 m (2H). C NMR, δ, ppm: 70.1, 99.8,
127.6, 128.3, 128.4, 129.1, 129.2, 131.8, 133.5, 134.0, 156.0. IR (KBr, cmꢀ1): 3313 (OH), 1651 (C=N),
984 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H12Cl3NONa 349.9877; Found 349.9863.
(Z)ꢀ3,3,3ꢀTrichloroꢀ1,2ꢀbis(2,5ꢀdimethylphenyl)propanꢀ1ꢀone oxime (3b). Obtained from 1b (30
mg, 0.16 mmol) and pꢀxylene (32 mg, 0.32 mmol). Purification by preparative TLC with mixture
petroleum ether – ethyl acetate, 95:5. Yield 30 mg (49%). Solid, mp 154ꢀ156°C. Structure confirmed by
single crystal Xꢀray analysis (see Supporting Information). 1H NMR, atropoisomer 1 (signals from the
spectrum of the mixture of isomers), δ, ppm: 1.70 s (3H, CH3), 2.07 s (3H, CH3), 2.34 s (3H), 2.36 s (3H,
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CH3), 5.25 s (1H), 7.83 s (1H). H NMR, atropoisomer 2 (signals from the spectrum of the mixture of
atropoisomers) δ, ppm: 2.07 s (3H, CH3), 2.15 s (3H, CH3), 2.29 s (3H, CH3), 2.34 s (3H), 5.07 s (1H),
7.74 s (1H). For the mixture of atropoisomers 1H NMR, δ, ppm: 6.92ꢀ7.12 m (10H), 8.04 s (2H, OH). 13C
NMR, atropoisomer 1 (signals from the spectrum of the mixture of atropoisomers) δ, ppm: 19.2, 19.9,
21.1, 21.3, 64.8, 100.0, 156.4. 13C NMR, atropoisomer 2 (signals from the spectrum of the mixture of
atropoisomers), δ, ppm: 19.4, 19.9, 20.9, 21.4, 63.9, 99.9, 156.8. For the mixture of atropoisomers 13C
NMR, δ, ppm: 126.7, 127.7, 129.7, 129.7, 129.8, 129.9, 130.0, 130.1, 130.5, 130.5, 131.0, 131.4, 131.4,
132.2, 132.5, 133.1, 133.5, 133.8, 134.8, 135.0, 135.3, 135.4, 135.7. IR (KBr, cmꢀ1) (mixture of
atropoisomers): 3326 (OH), 1613 (C=N), 989 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C19H20Cl3NONa 406.0530; Found 406.0516.
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(Z)ꢀ3,3,3ꢀTrichloroꢀ1,2ꢀbis(2,4,6ꢀtrimethylphenyl)propanꢀ1ꢀone oxime (3c). Obtained from 1b
(30 mg, 0.159 mmol) and mesitylene (1,3,5ꢀtrimethylbenzene) (38 mg, 0.32 mmol). Purification by
preparative TLC with mixture petroleum ether – ethyl acetate, 95:5. Yield 42 mg (65%). Solid, mp 156ꢀ
157°C. 1H NMR, δ, ppm: 1.73 s (3H), 1.98 s (3H), 2.21 s (3H), 2.22 s (3H), 2.51 s (3H), 2.79 s (3H), 5.40
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s (1H), 6.63 s (1H), 6.70 s (1H), 6.86 s (1H), 6.87 s (1H), 7.82 s (1H, OH). C NMR, δ, ppm: 19.9, 20.9,
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21.0, 21.1, 21.9, 24.1, 64.2, 100.6, 127.7, 128.7, 129.0, 129.6, 129.8, 132.1, 134.7, 136.9, 138.2, 138.5,
139.7, 140.5, 155.9. IR (KBr, cmꢀ1): 3338 (OH),1611 (C=N), 991 (N–O). HRMS (ESIꢀTOF) m/z: [M +
Na]+ Calcd for C21H24Cl3NONa 434.0816; Found 434.0824.
(Z)-3,3,3ꢀTrichloroꢀ1,2ꢀbis(2,3,5,6ꢀtetramethylphenyl)propanꢀ1ꢀone oxime (3d1), (Z)ꢀ3,3,3ꢀ
trichloroꢀ2ꢀ(2,3,4,5ꢀtetramethylphenyl)ꢀ1ꢀ(2,3,5,6ꢀtetramethylphehyl)propanꢀ1ꢀone oxime (3d2).
Obtained from 1b (30 mg, 0.159 mmol) and durene (1,2,4,5ꢀtetramethylbenzene) (42 mg, 0.32 mmol).
Purification by preparative TLC with mixture petroleum ether – ethyl acetate, 95:5. Yield 35 mg (50%).
Solid, mp 211ꢀ212°C. Structure of 3d1 and 3d2 confirmed by single crystal Xꢀray analysis (see
Supporting Information). 1H NMR 3d1 (signals from the spectrum of the mixture of isomers), δ, ppm:
1.57 s (3H, CH3), 1.77 s (3H, CH3), 1.98 s (3H, CH3), 2.11 s (3H, CH3), 2.19 s (3H, CH3), 2.23 s (3H,
CH3), 2.44 s (3H, CH3), 2.69 s (3H, CH3), 5.53 s (1H), 7.57 s (1H, OH), 7.62 s (1H), 7.64 s (1H). 1H NMR
3d2 (signals from the spectrum of the mixture of isomers), δ, ppm: 1.56 s (3H, CH3), 1.86 s (3H, CH3),
1.99 s (3H, CH3), 2.10 s (3H, CH3), 2.17 s (3H, CH3), 2.20 s (3H, CH3), 2.27 s (3H, CH3), 2.31 s (3H,
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CH3), 2.31 s (3H, CH3), 5.22 s (1H), 6.87 s (1H), 6.88 s (1H), 6.93 s (1H, OH). C NMR, 3d1 (signals
from the spectrum of the mixture of isomers), δ, ppm: 16.4, 16.9, 17.2, 17.4, 20.0, 20.1, 20.8, 21.9, 65.0,
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106.7, 128.6, 130.9, 132.2, 132.3, 133.9, 134.1, 134.4, 135.6, 136.0, 136.5, 157.3. C NMR 3d2 (signals
from the spectrum of the mixture of isomers), δ, ppm: 16.0, 16.5, 17.2, 17.4, 17.7, 20.0, 20.1, 21.0, 21.8,
63.2, 100.5, 130.0, 130.4, 132.1, 132.2, 132.7, 133.7, 134.1, 134.0, 135.0, 135.8, 157.0. IR (KBr, cmꢀ1)
(for mixture of isomers): 3375 (OH), 1714 (C=N), 984 (O–N). HRMS (ESIꢀTOF) m/z: [M + Na]+ (for
mixture of isomers) Calcd for C23H28Cl3NONa 462.1129; Found 462.1144.
(Z)ꢀ3,3,3ꢀTrichloroꢀ1,2ꢀbis(4ꢀmethoxyphenyl)propanꢀ1ꢀone oxime (3e1), (Z)ꢀ3,3,3ꢀTrichloroꢀ1ꢀ
(2ꢀmethoxyphenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)propanꢀ1ꢀone oxime (3e2). Obtained from 1b (30 mg, 0.16
mmol) and anisole (methoxybenzene) (34 mg, 0.32 mmol). Purification by preparative TLC with mixture
petroleum ether – ethyl acetate, 95:5. Yield 35 mg (54%). Solid, mp 153ꢀ155°C. Structure confirmed by
single crystal Xꢀray analysis (see Supporting Information). 1H NMR, 3e1 (signals from the spectrum of the
mixture of isomers), δ, ppm: 3.79 s (3H, OMe), 3.83 s (3H, OMe), 4.84 s (1H), 6.86 d (2H, J 8.8 Hz), 6.90
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d (2H, J 8.8 Hz), 7.20 d (2H, J 8.8 Hz) 7.58 d (2H, J 8.8 Hz), 7.87 s (1H, OH). H NMR, isomer 3e2
(signals from the spectrum of the mixture of isomers), δ, ppm: 3.69 s (3H, OMe), 3.82 s (3H, OMe), 4.85 s
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(1H), 6.85ꢀ6.91 m (6H), 7.54 d (2H, J 8.8 Hz), 7.78 s (1H, OH). 13C NMR, 3e1 (signals from the spectrum
of the mixture of isomers), δ, ppm: 55.3 (OMe), 69.4 (OMe), 100.4, 111.5, 113.3, 113.7, 113.8, 129.4,
133.0, 133.1, 155.7, 160.0, 160.2. 13C NMR, 3e2 (signals from the spectrum of the mixture of isomers), δ,
ppm: 55.6 (OMe), 68.6 (OMe), 100.4, 111.5, 120.4, 125.6, 126.2, 126.2, 130.0, 130.6, 154.7, 156.0,
159.9. IR (KBr, cmꢀ1) (for mixture of isomers): 3338 (OH), 1607 (C=N), 997 (O–N, isomer 1), 981 (O–N,
isomer 2). HRMS (ESIꢀTOF) m/z: [M + H]+ (for mixture of isomers) Calcd for C17H17Cl3NO3 388.0269;
Found 388.0279.
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(Z)ꢀ3,3,3ꢀTrichloroꢀ1,2ꢀbis(3,4ꢀdimethoxyphenyl)propanꢀ1ꢀone oxime (3f). Obtained from 1b
(30 mg, 0.16 mmol) and veratrol (1,2ꢀdimethoxybenzene) (44 mg, 0.32 mmol). Purification by preparative
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TLC with mixture petroleum ether – ethyl acetate, 1:1. Yield 30 mg (42%). Solid, mp 168ꢀ170°C. H
NMR, δ, ppm: 3.77 s (3H, OMe), 3.84 s (3H, OMe), 3.86 s (3H, OMe), 3.89 s (3H, OMe), 4.84 s (1H),
6.77 m (1H), 6.81ꢀ6.82 m (2 H), 6.84ꢀ6.87 m (1H), 7.16 dd (1H, J 8.3 Hz, J 2.1 Hz), 7.24 d (1H, J 2.0
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Hz), 8.28 s (1H, OH). C NMR, δ, ppm: 59.9 (2C, OMe), 56.0 (OMe), 56.2 (OMe), 69.7, 100.2, 110.6,
110.9, 111.4, 114.6, 120.7, 124.8, 126.0, 126.3, 148.6, 148.6, 149.7, 149.8, 155.6. IR (KBr, cmꢀ1): 3443
(OH), 1601 (C=N), 994 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C19H20Cl3NO5Na 470.0299;
Found 470.0315.
(Z)ꢀ3,3,3ꢀTribromoꢀ1,2ꢀdiphenylpropanꢀ1ꢀone oxime (4a). Obtained from 1c (100 mg, 0.31
mmol) and benzene (350 mg, 4.49 mmol). Yield 135 mg (95%). Solid, mp 137ꢀ138°C. Structure
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confirmed by single crystal Xꢀray analysis (see Supporting Information). H NMR, δ, ppm: 5.06 s (1H),
7.19ꢀ7.22 m (2H), 7.32ꢀ7.34 m (3H), 7.38ꢀ7.43 m (3H + 1OH), 7.77 d (2H, J 6.4 Hz). 13C NMR, δ, ppm:
42.8, 71.6, 127.6, 128.2, 128.4, 129.1, 129.2, 132.0, 134.2, 134.5, 157.1. IR (KBr, cmꢀ1): 3336 (OH), 1646
(C=N), 985 (N–O). HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H12Br3NONa 481.8361; Found
481.8359.
(Z)ꢀ3,3,3ꢀTribromoꢀ1,2ꢀbis(2,5ꢀdimethylphenyl)propanꢀ1ꢀone oxime (4b). Obtained from the
nitroalkene 1c (30 mg, 0.09 mmol) and pꢀxylene (19 mg, 0.18 mmol). Purification by preparative TLC
1
with mixture petroleum ether – ethyl acetate, 7:3. Yield 23 mg (48%). Solid, mp 80ꢀ82°C. H NMR,
atropoisomer 1 (signals from the spectrum of the mixture of atropoisomers), δ, ppm: 1.63 s (3H, CH3),
1
2.04 s (3H, CH3), 2.34 s (3H, CH3), 2.37 s (3H, CH3), 5.38 s (1H), 8.02 s (1H). H NMR, atropoisomer 2
(signals from the spectrum of the mixture of atropoisomers), δ, ppm: 2.03 s (3H, CH3), 2.13 s (3H, CH3),
2.34 s (3H, CH3), 2.39 s (3H, CH3), 5.17 s (1H), 6.01 s (1H), 7.93 s (1H). For the mixture of
atropoisomers 1H NMR, δ, ppm: 6.90 d (1H, J 7.76 Hz), 6.95ꢀ7.08 m (5H), 7.12 d (1H, J 6.48 Hz), 7.19 s
13
(1H), 7.38 m (2H). C NMR, isomer 1 (signals from the spectrum of the mixture of atropoisomers), δ,
ppm: 19.1, 20.0, 21.1, 21.3, 41.8, 66.4, 126.5, 129.7, 129.9, 130.0, 130.6, 130.9, 132.7, 133.7, 134.9,
29
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