3-nitro-2-phenyl-2-(Trifluoromethyl)-2h-chromenes: Synthesis and reactions with nucleophiles

Article abstract of DOI:10.1007/s10593-016-1971-y

A method is proposed for the synthesis of 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes by tandem condensation of salicylic aldehydes with (E)-3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene in the presence of triethylamine. The example of 3-nitro-2-phenyl

Full text of DOI:10.1007/s10593-016-1971-y

DOI 10.1007/s10593-016-1971-y
Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
3
-Nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes:
synthesis and reactions with nucleophiles
1
1
1
Alexey Yu. Barkov , Vladislav Yu. Korotaev *, Ivan V. Kotovich ,
1
1
1
Nikolai S. Zimnitskiy , Igor B. Kutyashev , Vyacheslav Ya. Sosnovskikh
1
Institute of Natural Sciences, Ural Federal University named after the First President of Russia B. N. Yeltsin,
1 Lenina Ave., Yekaterinburg 620000, Russia; е-mail: korotaev.vladislav@urfu.ru
5
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
016, 52(10), 814–822
Submitted August 26, 2016
Accepted September 20, 2016
2
A method is proposed for the synthesis of 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes by tandem condensation of salicylic
aldehydes with (E)-3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene in the presence of triethylamine. The example of 3-nitro-2-phenyl-
2
-(trifluoromethyl)-2H-chromene was used to demonstrate conjugated addition reactions with enamines, nitromethane, and aniline,
which are characteristic for this class of compounds. The structure of the obtained products was confirmed by X-ray structural analysis.
Keywords: 3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene, 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes, salicylic aldehydes, 2,2,3,4-
tetrasubstituted chromanes, diastereoselectivity, nucleophilic addition.
3
-Nitro-2H-chromenes represent an important class of
1 (Fig. 1), the reactivity of which toward nucleophiles
organic compounds, the properties of which have been
significantly exceeded1 the previously known 3-nitro-
1
intensively studied in recent years. The interest toward
2-phenyl-2Н-chromenes 2, due to the presence of a CF
3
these heterocycles as starting substrates for the preparation
of more complex bioactive molecules is linked to their
availability and high reactivity, as well as the common
occurrence of many derivatives of chromene and chromane
group providing an additional strong negative inductive
effect, thus activating the double bond in pyran ring.
Besides that, the addition reactions involving 2-(trifluoro-
methyl)chromenes 1 were found to be more stereoselective,
compared to the analogous reactions of 2-phenylchromenes
2, allowing us to obtain a wide range of new 2,3,4-tri-
substituted chromanes as individual diastereomers, the
structures of which were reliably established by X-ray
structural analysis.3
(
3,4-dihydro-2H-1-benzopyran) in plants. Such compounds
2
show promise as pesticides and potential drug molecules.
The reactivity of 3-nitro-2H-chromenes is mostly
determined by the nitroalkene moiety, although the
substituent at position 2 can also substantially affect the
rate and direction of some reactions, even though it is
The introduction of a bulky phenyl substituent along
3
bonded to sp -hybridized carbon atom. For example, we
with the CF group at position 2 of chromenes 1 was
3
recently studied 3-nitro-2-(trifluoromethyl)-2H-chromenes
clearly of interest, as it allowed to obtain 3-nitro-2-phenyl-
0
009-3122/16/52(10)-0814©2016 Springer Science+Business Media New York
814

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
NO2
NO2
Scheme 1
R
R
O
CF3
O
Ph
1
2
NO2
CF3
R
O
Ph
3
Figure 1. 2-Substituted 3-nitro-2Н-chromenes 1–3.
2-(trifluoromethyl)-2H-chromenes 3 that represented a
combination of chromenes 1 and 2 (Fig. 1). The structural
features of compounds 3 can not only increase the
stereoselectivity of addition reactions involving these
compounds and to expand the range of stereochemically
different 2,2,3,4-tetrasubstituted chromanes, but also lead
to the emergence of new, useful properties of chromenes
themselves, as well as in products obtained from them.
The most common method that has been used for
obtaining 3-nitro-2H-chromenes is based on the reaction of
salicylic aldehydes with conjugated nitroalkenes in the
presence of bases, due to the wide availability of these
Table 1. Yields of nitrochromenes 3a–g
Chromene
R
H
Yield, %
96
3
a
3
b
6-Cl
6-Br
6,8-Br
6-Me
64
3c
69
3
d
2
95
1
starting materials. The process represented a nucleophilic
3
e
80
addition of the respective phenolate anion to nitroalkene
molecule, followed by intramolecular Henry reaction and
led to the formation of 4-hydroxy-3-nitrochromane,
dehydration of which provided the desired product
3
f
6-OMe
8-OEt
95
3g
89
(
Scheme 1). This approach can be used for the synthesis of
3
a wide range of nitrochromenes containing various
substituents both at position 2 of the pyran system and in
the aromatic ring.
methyl group bonded to sp carbon atom was observed in
1
9
F NMR spectra of chromenes 3a–g as a singlet at 88.8–
89.5 ppm, which was shifted downfield compared to
(83.9–84.3 ppm),3
a−c,4a,5b
due to the
In a continuation of our efforts directed toward the
chromenes
1
4
5
13
synthesis and understanding of the chemical properties of
deshielding effect of 2-phenyl substituent. C NMR
3
-nitro-2-(trifluoromethyl)-2H-chromenes 1, in the current
spectra of compounds 3a–g featured quartets of the CF
3
work we propose a method for the preparation of
previously unknown 3-nitro-2-phenyl-2-(trifluoromethyl)-
group and the С-2 atom in the ranges of 123.2−123.7 and
82.4−83.7 ppm, respectively, with the spin-spin coupling
1
2
2
H-chromenes 3 and describe representative reactions of N-
constants of JCF = 289.4−290.6 and JCF = 30.8−31.3 Hz,
as well as a quartet or broadened singlet of the Сipso atom in
and C-nucleophiles with a compound of this class, which
lacks substituents in the benzene ring.
3
the phenyl substituent at 127.2−127.4 ppm ( JCF = 1.0−1.5 Hz).
Nitrochromenes 3a–g were synthesized from the
corresponding salicylic aldehydes and (E)-3,3,3-trifluoro-
IR spectra of the obtained compounds contained absorption
bands due to the stretching vibrations of double bond at
1631−1641 cm–1 and the olefinic nitro group at 1519−1528
1
-nitro-2-phenylprop-1-ene, obtained by Henry reaction
–1
from trifluoroacetophenone and nitromethane, followed by
dehydration of the formed nitro alcohol with thionyl
and 1289−1342 cm . The structure of nitrochromene 3a
was confirmed by X-ray structural analysis (Fig. 2).
6
chloride in the presence of pyridine. The synthesis of
We further studied the interaction of 3-nitro-2-phenyl-2-(tri-
fluoromethyl)-2H-chromene (3a) with primary and tertiary
push-pull enamines, which were synthesized from
acetoacetic ester and acetylacetone. It was found that ethyl
(Z)-3-aminocrotonate (4), similarly as in the case of 3-nitro-
chromenes 3a,d–g was performed in dichloromethane at
room temperature for 3 h, using triethylamine as base. The
formation of 4-hydroxy-3-nitrochromane intermediate was
not observed, and the yields of chromenes 3a,d–g reached
7
8
3
5
0–96% (Scheme 1, Table 1). Additional refluxing for
min was required for obtaining chromenes 3b,c from
-chloro- and 5-bromosalicylic aldehydes, while their
2-(trifluoromethyl)-2H-chromenes 1, added with its most
nucleophilic α-carbon atom at position 4 of chromene 3a
that was activated by nitro group, forming 2,2,3,4-
tetrasubstituted chromane 5 in 74% yield as an individual
trans,trans-diastereomer tt-5 with (Z)-configuration of the
enaminoester moiety, stabilized by intramolecular hydrogen
bond. The reaction was performed by brief heating in
anhydrous acetonitrile, followed by maintaining at room
temperature for 3 days (Scheme 2).
yields were lower (64–69%).
Chromenes 3a–g were isolated as yellow fine crystalline
1
powders. H NMR spectra of these compounds contained a
characteristic singlet of 4-CH proton in the range of 8.07–
8
8
.24 ppm. The diastereotopic methylene protons in
-ethoxychromene 3g were observed as two double
quartets at 4.07 and 4.11 ppm, pointing to the presence of
asymmetric carbon atom in the molecule. The trifluoro-
The trans-diequatorial configuration of nitro group and
enaminoester moiety was identified from the large value of
8
15

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
Scheme 2
spin-spin coupling constant between 3-CH and 4-CH
1
protons (J3,4 = 11.7 Hz), observed in H NMR spectrum of
compound 5 in CDCl
3
solution. The presence of
intramolecular hydrogen bond both in solution and solid
state, associated with the (Z)-configuration of double bond,
was evident from the broadened singlet of NH proton in the
downfield region (8.94 ppm) and from the presence of
–
1
ν(NH) absorption band at 3490 cm in the IR spectrum of
chromane 5. The CF group was observed as a singlet in
3
1
9
F NMR spectrum of this compound at 85.6 ppm.
The validity of conclusions about the structure of
compound 5 that were reached from the examination of
spectral data, as well as the relative configuration of
substituents at the C-2 atom were confirmed by
monocrystal X-ray structural analysis of this chromane,
proving its trans,trans configuration at С-2, С-3, and С-4
atoms (tt-isomer). As shown in Figure 3, all three bulky
Figure 2. The molecular structure of compound 3a with atoms
represented by thermal vibration ellipsoids of 30% probability.
substituents in the heterocycle (CF
3
, NO , and the
2
enaminoester group) occupied equatorial positions, while
the planar phenyl substituent at the C-2 carbon atom and
the 3,4-CH hydrogen atoms were axially oriented. The
unfavorable steric interactions between the bulky
substituents caused the pyran ring to assume a twisted half-
chair conformation. The planarity of enaminoester moiety
was caused by the presence of an intramolecular hydrogen
bond between the hydrogen atom of amino group and the
carbonyl oxygen atom, with the interatomic distances
N(2)–H(2A) 0.90(2), H(2A)···O(5) 1.96(2), N(2)···O(5)
2
.660(3) Å, and the angle N(2)–H(2A)···O(5) 133(2)°. The
plane of enaminoester moiety was nearly orthogonal to the
aromatic ring plane (the dihedral angle between these
planes was equal to 85.8(2)°).
It should be noted that chromane tt-5 both in crystalline
state (Fig. 3) and in solution phase (as indicated by the
1
19
presence of one set of signals in H and F NMR spectra)
existed in the form of the energetically favored
atropoisomer with anti configuration of the 4-CH atom and
Figure 3. The molecular structure of compound tt-5 with atoms
represented by thermal vibration ellipsoids of 30% probability.
the CO Et group, due to the hindered rotation around the
С(4)–С(2') bond (Scheme 2).
2
7
In contrast to the primary (Z)-enaminoester 4, the interaction
of chromene 3a with tertiary (E)-enamino ketone 6 under
analogous conditions occurred with the participation of
vinylogous β-methyl group and led to the formation of
cis,trans-chromane 7 in 49% yield. The reaction time could
be shortened to 5 h, if the process was performed at 60°С
(6.00 ppm) and a broadened singlet of the 3-СН proton
(5.26 ppm); the signal of the 4-СН proton overlapped with
the signals of morpholine CH
2
OCH protons. The similar
2
chemical shifts of 3-СН proton and spin-spin coupling
constant J3,4 ≈ 0 Hz were earlier observed in the case of
(
Scheme 3). Chromenes 1 reacted with enamino ketone 6 in
cis,trans-2,3,4-trisubstituted 2-CX -chromanes 8 (X = F, Cl),
3
3
c
analogous way.
the structure of which has been definitely proved by X-ray
1
3c
H NMR spectrum of compound 7 contained two double
structural analysis. Based on this, we can propose that the
doublets of diastereotopic methylene protons at 3.19 and
same cis,trans configuration and preferred conformation
2
3
.71 ppm, with spin-spin coupling constants of J = 13.1 Hz;
with cis configuration of equatorial CF group and trans
3
3
J = 3.0 and 2.5 Hz, respectively, a singlet of the =СН proton
configuration of pseudoaxial aminoenone moiety relative to
8
16

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
Scheme 3
Scheme 5
the axial nitro group also existed in the molecule of
chromane ct-7, with the only difference that the axial
position was occupied by phenyl substituent instead of the
1
9
2
-СН proton (Scheme 4). The CF
spectrum of compound ct-7 was manifested as a singlet at
5.1 ppm.
3
group in the F NMR
8
Scheme 4
diastereomer tc-10a is presented in Figure 4, and it is
obvious that the bulkiest enamine moiety of the molecule
occupies an equatorial position, while the CF
3
and NO
2
groups are arranged in a trans-diaxial configuration
trans,cis-isomer). The pyran ring, similarly as in chromane
(
tt-5, exists in a twisted half-chair conformation. A similar
conformation of heterocycles was identified also in
chromane cc-10b, and in that case both of the bulky
substituents (CF and enamine group) occupied equatorial
3
positions (cis,cis-isomer) (Fig. 5). The phenyl substituent in
enamine group deviated by 80.7(3)° from the plane of double
bond in isomer tc-10a and by −67.7(3)° in the isomer cc-10b,
while the nitrogen atom of morpholine ring in both
molecules only slightly deviated from this plane, as indicated
by the 3(1)° value of the torsion angle N(2)–C(18)–C(17)–H(17)
in chromane 10a and −7(2)° value of the torsion angle
N(1)–C(18)–C(17)–H(18) in chromane 10b. The planes of
chromane system benzene ring and the enamine moiety in
compounds 10a,b were rotated one relative to the other by
−74.3(3) and 78.5(3)°, respectively.
Chromene 3a readily reacted with α-morpholinostyrene
9) in acetonitrile solution, giving a good yield of the
(
The diastereomers tc-10a and cc-10b were characterized
by similar chemical shift values of the 3-СН proton (5.40 and
5.32 ppm, respectively) and the spin-spin coupling constant
respective 2,2,3,4-tetrasubstituted chromane 10. It is
interesting to note that the spatial structure of this product
substantially depended on the temperature regime. For
example, when the reaction was performed at room
temperature for 1 day, a 3:1 mixture of stereoisomeric
chromanes 10a and 10b was formed in 96% yield, from
which the major isomer 10a could be isolated as pure
sample by simple recrystallization from a mixture of
dichloromethane–hexane (2:1). At the same time, the
chromane 10b was formed in 71% yield by heating a
mixture of chromene 3а and enamine 9 for 4 h in
acetonitrile at 60°С (Scheme 5). It is logical to assume that
the isomer 10a resulted from kinetic control, and was
transformed upon heating via a retro-Michael reaction to
the thermodynamically more stable isomer 10b. We have
previously identified and studied a similar transformation
J
3,4 (5.6 and 5.4 Hz, respectively), while the signal of the
4-СН proton in the spectrum of chromane tc-10a was
observed at lower field (4.07 ppm), compared to the
spectrum of chromane cc-10b (3.39 ppm). This fact can be
explained by the preferred existence of compound tc-10a as
conformer with axial CF group both in solid state (Fig. 4)
3
and in solution phase, while the same group preferred an
equatorial position in isomer cc-10b both in crystal
structure (Fig. 5) and in solution. For this reason, the
pseudoaxial 4-СН proton in the isomer cc-10b was located
in the region shielded by axial phenyl substituent, resulting
1
19
in an upfield shift of its H NMR signal. F NMR signals
of CF group in the stereoisomeric products tc-10a and
3
cc-10b were observed as singlets at 87.2 and 84.2 ppm,
respectively (Scheme 6, Table 2).
3
e
in the series of 3-nitro-2-(trihalomethyl)-2H-chromenes.
The spatial structure of compounds 10a,b was
established by X-ray structural analysis. The structure of
In contract to the diastereoselective reactions of enamines
described above, the interaction of nitrochromene 3a with
8
17

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
Figure 4. The molecular structure of compound tc-10a with
atoms represented by thermal vibration ellipsoids of 30%
probability.
Figure 5. The molecular structure of compound cc-10b with
atoms represented by thermal vibration ellipsoids of 30%
probability.
Scheme 6
4
-CH proton in cc-isomers of chromanes 11 and 12 was
5
.40
Ph
NO2
shielded by the phenyl substituent and its signal was shifted
R
F3C
H
upfield relative to the analogous signal of tc-isomer (Δδ =
0
R
O
O
H
.73–0.77 ppm). As expected, the largest spin-spin
NO
Ph
2
H
coupling constant J3,4 = 11.7 Hz was observed for
chromane tt-5 with trans-diaxially oriented 3-СН and 4-СН
protons. The moderate values of J3,4 = 4.9–5.6 Hz were
characteristic for the tc- and cс-isomers with axially-
equatorial hydrogen atoms, while J3,4 ≈ 0 Hz in ct-isomers,
where the 3-СН and 4-СН protons were oriented trans-
4
.07
H
CF
3
tc-10a
J3,4 = 5.6 Hz
87.7
Ph
H
3
.39
8
4.2
H
NO2
F3C
O
O
Ph
H
R
diequatorially. The axial CF group in tc-isomer was
3
H5
NO2
R
deshieded by the phenyl ring, resulting in a downfield shift
of its 19F NMR signal by 2.8–3.8 ppm, compared to the
other isomers. This feature enabled rapid detection of
.32
CF3
cc-
1
0b
J3,4 = 5.4 Hz
19
tc-isomer in the reaction mixture by F NMR spectro-
nitromethane in the presence of
K
2
CO
3
at room
scopy. The situation changed to the opposite in cc-isomers,
temperature without solvent after 2 days led to the formation
of a mixture of three out of the four possible stereoisomers
of 3-nitro-4-(nitromethyl)-2-phenyl-2-(trifluoromethyl)chro-
mane (11) in the ratio of ct-11a : cc-11b : tc-11c = 44:38:18,
and 77% yield. Analogous diastereomers of 2,2,3,4-tetra-
substituted chromanes were obtained in a total yield of
where the equatorial CF group was shielded by the phenyl
3
substituent. In that case, its signal was slightly (by 0.4 ppm)
shifted upfield relative to the signal of ct-isomer (Table 2).
Thus, 3-nitro-2-phenyl-2-(trifluoromethyl)-2H-chromenes
served as readily available and highly reactive substrates in
a series of reactions with C- and N-nucleophiles, which
3
7% by reacting chromene 3a with aniline at 100°C for 2 h,
albeit at a different isomer ratio of ct-12a : cc-12b : tc-12c =
Table 2. The characteristic signals in Н and 19F NMR spectra of
compounds 5, 7, 10a,b, 11a–c, 12a–c
1
9
:36:55 (Scheme 7).
The relative molecular configurations of products 11a–c
and 12a–c were successfully established by NMR
spectroscopy, based on the results obtained for the
individual stereoisomers ct-7, tc-10a, and cc-10b. For
example, 1H NMR spectra of ct-isomers 11a and 12a
contained the signal of 3-СН proton as only slightly
broadened singlet (5.94 ppm, J3,4 ≈ 0). The pairs of
compounds tc-11c, tc-12с and cc-11b, сс-12b showed close
values of spin-spin coupling constants (J3,4 = 4.9–5.6 Hz),
1Н NMR spectrum, δ, ppm
19F NMR spectrum, δ, ppm
CF
Chromane
3-СН
4-СН
J3,4, Hz
3
tt-5
6.18
5.26
5.40
5.32
5.94
6.06
6.04
5.94
6.08
6.12
4.12
–*
11.7
≈ 0
5.6
5.4
≈ 0
4.9
5.1
≈ 0
5.2
5.6
85.6
85.1
87.2
84.2
85.0
84.6
88.0
84.6
84.2
87.8
ct-7
tc-10a
cc-10b
ct-11a
cc-11b
tc-11c
ct-12a
cc-12b
tc-12c
4.07
3.39
4.12
3.85
4.58
4.69
4.72
5.49
19
but different F NMR chemical shifts of СF group (87.8–
3
8
8.0 ppm in tc-isomers and 84.2–84.6 ppm in cc-isomers)
(
Table 2).
It should be noted that the chemical shifts of 3,4-СН
protons and CF group along with the vicinal spin-spin
3
coupling constant J3,4 had a diagnostic value and could be
useful for establishing the relative configurations of
stereoisomeric chromanes via NMR spectroscopy. The
* Signal was not detected due to overlapping.
8
18

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
Scheme 7
allowed us to demonstrate the utility of such substrates for
diastereoselective synthesis of new 2,2,3,4-tetrasubstituted
chromanes.
6-Chloro-3-nitro-2-phenyl-2-(trifluoromethyl)-2H-
chromene (3b). Yield 0.23 g (64%), mp 77–78°C. IR
−
1
spectrum, ν, cm : 1634, 1566, 1525, 1474, 1451, 1420,
1
1
332. H NMR spectrum, δ, ppm (J, Hz): 6.95 (1H, d,
Experimental
J = 8.3, H-8); 7.35 (1H, d, J = 2.3, H-5); 7.38 (1H, dd,
J = 8.3, J = 2.3, H-7); 7.40–7.46 (3H, m, H Ph); 7.57–7.64
(2H, m, H Ph); 8.14 (1H, s, 4-CH). F NMR spectrum, δ, ppm:
IR spectra were recorded on
a
Bruker 1 Alpha
19
spectrometer with ATR accessory (ZnSe crystal). Н and
1
9
F NMR spectra were acquired on a Bruker DRX-400
spectrometer (400 and 376 MHz, respectively) in CDCl
89.0 (s, CF
ClF NO
6-Bromo-3-nitro-2-phenyl-2-(trifluoromethyl)-2H-
chromene (3c). Yield 0.28 g (69%), mp 74–75°C. IR
spectrum, ν, cm : 1632, 1560, 1525, 1472, 1415, 1331. H
NMR spectrum, δ, ppm (J, Hz): 6.90 (1H, d, J = 8.6, H-8);
7.38–7.46 (3H, m, H Ph); 7.49 (1H, d, J = 2.4, H-5); 7.52
(1H, dd, J = 8.6, J = 2.4, H-7); 7.56–7.65 (2H, m, H Ph);
8.14 (1H, s, 4-CH). 13C NMR spectrum, δ, ppm (J, Hz):
82.6 (q, J = 30.8, C-2); 115.4; 118.0; 118.2; 123.5 (q,
3
). Found, %: C 54.08; Н 2.37; N 3.96.
3
3
,
C
16
H
9
3
. Calculated, %: C 54.03; Н 2.55; N 3.94.
1
3
using TMS and C
spectra were acquired on
spectrometer (126 MHz) in CDCl
6
F as internal standards. C NMR
6
a
Bruker Avance 500
with TMS as internal
−
1
1
3
standard. Elemental analysis was performed on a PE 2400
automatic analyzer. Melting points were determined on an
SMP40 apparatus.
The starting (E)-3,3,3-trifluoro-1-nitro-2-phenylprop-
1
-ene was synthesized according to a published procedure.6
Synthesis of nitrochromenes 3a–g (General method).
J = 290.2, CF
132.4; 134.6; 137.6; 139.8; 151.5. F NMR spectrum, δ, ppm:
89.0 (s, CF ). Found, %: C 48.09; Н 2.14; N 3.48.
BrF NO . Calculated, %: C 48.03; Н 2.27; N 3.50.
6,8-Dibromo-3-nitro-2-phenyl-2-(trifluoromethyl)-
3
); 127.2 (q, J = 1.5); 128.6; 129.9; 132.1;
19
Anhydrous Et N (0.014 ml, 0.1 mmol) was added to a
3
solution of the appropriate salicylic aldehyde (1.0 mmol)
3
and (E)-3,3,3-trifluoro-1-nitro-2-phenylprop-1-ene (0.24 g,
C
16
H
9
3
3
1
.1 mmol) in anhydrous CH
2
Cl (3 ml), and the mixture
2
was maintained at room temperature for 3 h. In the case of
-chloro- and 5-bromosalicylic aldehydes, the mixture after
addition of Et N was at first refluxed for 3 min, then left
2H-chromene (3d). Yield 0.46 g (95%), mp 151–152°C.
−1
5
IR spectrum, ν, cm : 1635, 1550, 1527, 1407, 1289.
1
3
H NMR spectrum, δ, ppm (J, Hz): 7.26 (1H, d, J = 2.1,
for 3 h at room temperature. After the reaction was
complete, the solvent was removed at reduced pressure, the
residue was recrystallized from MeOH (compound 3d) or
from ethanol (the rest of the compounds), and the target
compounds were isolated as yellow powders.
H-5(7)); 7.36–7.48 (3H, m, H Ph); 7.57–7.66 (2H, m,
H Ph); 7.76 (1H, d, J = 2.1, H-7(5)); 8.07 (1H, s, 4-CH).
13
C NMR spectrum, δ, ppm (J, Hz): 83.7 (q, J = 31.3, C-2);
111.6; 115.6; 119.4; 123.2 (q, J = 289.4, CF
128.6; 130.2; 131.3; 131.4; 133.6; 139.9; 141.1; 148.4.
3
); 127.3 (br. s);
19
3
-Nitro-2-phenyl-2-(trifluoromethyl)-2H-chromene (3a).
F NMR spectrum, δ, ppm: 89.5 (s, CF
Н 1.64; N 2.89. C16
Н 1.68; N 2.92.
3
). Found, %: C 40.20;
−
1
Yield 0.31 g (96%), mp 141–142°C. IR spectrum, ν, cm :
H
8
Br
2
F
3
NO
3
. Calculated, %: C 40.12;
1
1
640, 1608, 1570, 1519, 1483, 1455, 1330, 1314. H NMR
spectrum, δ, ppm (J, Hz): 6.99 (1H, br. d, J = 8.2, H-8);
6-Methyl-3-nitro-2-phenyl-2-(trifluoromethyl)-2H-
chromene (3e). Yield 0.27 g (80%), mp 96–97°C. IR
7
.09 (1H, td, J = 7.5, J = 1.0, H-6); 7.37 (1H, dd, J = 7.6,
−
1
J = 1.6, H-5); 7.40–7.43 (3H, m, H-3,4,5 Ph); 7.44 (1H,
ddd, J = 8.2, J = 7.4, J = 1.6, H-7); 7.60–7.67 (2H, m, H-2,6
spectrum, ν, cm : 1634, 1575, 1522, 1487, 1422, 1332.
1
H NMR spectrum, δ, ppm (J, Hz): 2.32 (3H, s, CH ); 6.88
3
13
Ph); 8.24 (1H, s, 4-CH). C NMR spectrum, δ, ppm (J, Hz):
(1H, d, J = 8.3, H-8); 7.14 (1H, br. d, J = 1.6, H-5); 7.23
(1H, dd, J = 8.3, J = 1.6, H-7); 7.34–7.46 (3H, m, H Ph);
8
2.4 (q, J = 30.9, C-2); 116.2; 116.3; 123.4; 123.7 (q,
J = 290.6, CF ); 127.2 (q, J = 1.4); 128.5; 129.6; 130.5;
33.7; 135.2; 135.3; 138.8; 152.6. F NMR spectrum, δ, ppm:
8.8 (s, CF ). Found, %: C 59.80; Н 3.12; N 4.30.
NO . Calculated, %: C 59.82; Н 3.14; N 4.36.
19
3
7.55–7.69 (2H, m, H Ph); 8.19 (1H, s, 4-CH). F NMR
19
1
spectrum, δ, ppm: 88.9 (s, CF
3
). Found, %: C 61.23;
8
3
Н 3.55; N 4.18. C17
H
12
F
3
NO
3
. Calculated, %: C 60.90;
C
16
H
10
F
3
3
Н 3.61; N 4.18.
8
19

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
6
-Methoxy-3-nitro-2-phenyl-2-(trifluoromethyl)-2H-
solvent was removed at reduced pressure, the residue was
chromene (3f). Yield 0.33 g (95%), mp 101–102°C. IR
treated with anhydrous Et O (5 ml). The precipitate formed
2
−
1
spectrum, ν, cm : 1641, 1576, 1525, 1487, 1454, 1429,
was filtered off and washed with hexane (3×0.5 ml). Yield
0.24 g (49%), white powder, mp 202–203°C (decomp.). IR
1
1
332, 1308. H NMR spectrum, δ, ppm (J, Hz): 3.81 (3H,
−
1
s, OCH
3
); 6.84 (1H, d, J = 2.9, H-5); 6.93 (1H, d, J = 8.9,
spectrum, ν, cm : 1658, 1636, 1563, 1535, 1490, 1446,
1
H-8); 6.99 (1H, dd, J = 8.9, J = 2.9, H-5); 7.37–7.45 (3H,
1367, 1321. H NMR spectrum, δ, ppm (J, Hz): 2.10 (3H,
m, H-3,4,5 Ph); 7.58–7.66 (2H, m, H-2,6 Ph); 8.18 (1H, s,
s, CH
3
); 2.62 (4H, br. s, CH
2
NCH ); 3.19 (1H, dd, J = 13.1,
2
4
-CH). 13C NMR spectrum, δ, ppm (J, Hz): 55.8; 82.4 (q,
J = 3.0) and 3.71 (1H, dd, J = 13.1, J = 2.5, CH
3.40 (5H, m, 4-CH, CH OCH ); 5.26 (1H, br. s, 3-СН); 6.00
2
CH); 3.23‒
J = 30.9, C-2); 113.7; 116.8; 117.1; 121.4; 123.7 (q,
J = 290.6, CF ); 127.2 (br. s); 128.4; 129.6; 133.7; 135.1;
39.6; 146.6; 155.3. F NMR spectrum, δ, ppm: 89.1 (s,
CF ). Found, %: C 57.91; Н 3.59; N 3.93. C17 NO
Calculated, %: C 58.13; Н 3.44; N 3.99.
-Ethoxy-3-nitro-2-phenyl-2-(trifluoromethyl)-2H-
chromene (3g). Yield 0.33 g (89%), mp 90–91°C. IR
2
2
3
(1H, s, =CH–COMe); 6.89 (1H, d, J = 7.7, H-8); 6.94 (1H, t,
J = 7.7, H-6); 7.25 (1H, d, J = 7.9, H-5); 7.32 (1H, t,
J = 7.6, H-7); 7.37–7.45 (3H, m, H-3,4,5 Ph); 7.61 (2H, d,
1
9
1
3
H
12
F
3
4
.
13
J = 7.6, H-2,6 Ph). C NMR spectrum, δ, ppm (J, Hz):
31.8; 35.0; 38.2; 46.5; 65.6; 79.6 (q, J = 30.7, C-2); 84.2;
8
96.5; 117.2; 119.9; 122.1; 122.7 (q, J = 286.0, CF ); 127.4;
3
−
1
spectrum, ν, cm : 1631, 1606, 1574, 1528, 1473, 1396,
129.1; 129.2; 129.6; 130.2; 132.7; 150.3; 161.8; 194.7.
1
19
1
342, 1323. H NMR spectrum, δ, ppm (J, Hz): 1.38 (3H, t,
J = 7.0, OCH CH ); 4.07 (1H, dq, J = 9.8, J = 7.0) and 4.11
1H, dq, J = 9.8, J = 7.0, OCH CH ); 6.94 (1H, dd, J = 7.5,
F NMR spectrum, δ, ppm: 85.1 (s, CF
3
). Found, %: C 61.06;
2
3
Н 5.27; N 5.63. C25
Н 5.14; N 5.71.
H
25
F
3
N
2
O
5
. Calculated, %: C 61.22;
(
2
3
J = 1.6, H-7); 6.99 (1H, t, J = 7.8, H-6); 7.05 (1H, dd,
J = 8.0, J = 1.6, H-7); 7.36–7.44 (3H, m, H-3,4,5 Ph); 7.61–
.69 (2H, m, H-2,6 Ph); 8.17 (1H, s, 4-CH). C NMR
4-{(E)-2-(2S*,3S*,4S*)-[3-Nitro-2-phenyl-2-(trifluoro-
methyl)chroman-4-yl]-1-phenylvinyl}morpholine (tc-10a).
A mixture of chromene 3a (0.32 g, 1.0 mmol) and
α-morpholinostyrene (9) (0.19 g, 1.0 mmol) was dissolved
in anhydrous MeCN (0.5 ml) and maintained at room
temperature for 1 day. The obtained solid product was
filtered off and washed with hexane, providing chromane
tc-10a as a 3:1 mixture with isomer cc-10b. Yield of the
isomer mixture was 0.47 g (96%), beige powder, mp 202–
203°C (decomp.). Recrystallization from a system of
1
3
7
spectrum, δ, ppm (J, Hz): 14.7; 65.5; 82.7 (q, J = 31.0,
C-2); 117.7; 120.4; 122.2; 123.4; 123.6 (q, J = 289.7, CF );
27.4 (q, J = 1.0); 128.4; 129.6; 133.7; 134.8; 139.7; 142.3;
3
1
1
47.3. 19F NMR spectrum, δ, ppm: 89.2 (s, CF
). Found, %:
. Calculated, %:
3
C 59.34; Н 3.86; N 3.87. C18
C 59.18; Н 3.86; N 3.83.
H
14
F
3
NO
4
Ethyl (Z)-3-amino-2-[(2S*,3S*,4S*)-3-nitro-2-phenyl-
-(trifluoromethyl)chroman-4-yl]but-2-enoate (tt-5). A
2
CH
2
Cl –hexane, 2:1, gave the individual isomer tc-10a.
2
mixture of chromene 3a (0.32 g, 1.0 mmol) and ethyl (Z)-3-
aminocrotonate (4) (0.13 g, 1.0 mmol) in anhydrous MeCN
Yield 0.33 g (67%), light-yellow powder, mp 204‒205°C.
−1
IR spectrum, ν, cm : 1616, 1584, 1485, 1453, 1382, 1360.
1
(
1 ml) was heated until dissolution at 50°C (3 min) and
H NMR spectrum, δ, ppm (J, Hz): 2.77–2.90 (4H, m,
then maintained at room temperature for 3 days. The
CH
2
NCH
2
); 3.66–3.75 (4H, m, CH
2
OCH ); 4.07 (1H, dd,
2
obtained solid product was filtered off and recrystallized
J = 9.4, J = 5.6, 4-СН); 4.20 (1H, d, J = 9.4, =CH–CPh);
5.40 (1H, d, J = 5.6, 3-СН); 7.06 (1H, td, J = 7.5, J = 1.1,
H-6); 7.14 (1H, dd, J = 8.2, J = 1.1, H-8); 7.28 (1H, dddd,
J = 8.2, J = 7.8, J = 1.5, J = 1.0, H-7); 7.31–8.01 (11H, m,
from a system of CH
2
Cl –hexane, 1:2. Yield 0.33 g (74%),
2
−1
white powder, mp 165–166°C. IR spectrum, ν, cm : 3490,
319, 1659, 1613, 1585, 1556, 1512, 1485, 1454, 1369.
3
1
13
H NMR spectrum, δ, ppm (J, Hz): 0.88 (3H, t, J = 7.1,
OCH CH ); 1.91 (3H, s, CH ); 3.85 (1H, dq, J = 10.7,
J = 7.1) and 3.96 (1H, dq, J = 10.7, J = 7.1, OCH CH );
H-5, H Ph). C NMR spectrum, δ, ppm (J, Hz): 35.6 (q,
2
3
3
J = 1.7); 49.0; 66.7; 78.7 (q, J = 28.8, C-2); 85.8; 96.9;
2
3
116.0; 120.5; 122.2; 123.4 (q, J = 290.1, CF ); 127.7;
3
4
(
(
.12 (1H, d, J = 11.7, 4-CH); 4.78 (1H, br. s, NH); 6.18
128.5; 128.7; 128.8; 128.9; 129.7; 132.4; 136.1; 152.0;
19
1H, d, J = 11.7, 3-CH); 6.91–6.98 (2H, m, H-6,8); 7.11
1H, d, J = 8.1, H-5); 7.21–7.23 (1H, m, H-7); 7.34 (2H, t,
156.2 (two carbon atoms were not observed). F NMR
spectrum, δ, ppm: 87.2 (s, CF
3
). Found, %: C 65.97;
J = 7.6, H-3,5 Ph); 7.40 (1H, tt, J = 7.3, J = 1.2, H-4 Ph);
Н 4.89; N 5.45. C28
H
25
F
3
N
2
O
4
. Calculated, %: C 65.88;
13
7
.50 (2H, d, J = 7.9, H-2,6 Ph); 8.94 (1H, br. s, NH).
NMR spectrum, δ, ppm (J, Hz): 13.7; 21.3; 37.6; 59.0; 81.4
q, J = 29.7, C-2); 85.5; 87.7; 116.2; 122.6; 123.5 (q,
J = 286.1, CF ); 124.2; 127.0; 127.7 (q, J = 1.6); 128.3;
29.8; 130.9; 151.0; 162.1; 168.7 (one carbon atom was
C
Н 4.94; N 5.49.
4-{(E)-2-(2S*,3R*,4R*)-[3-Nitro-2-phenyl-2-(trifluoro-
methyl)chroman-4-yl]-1-phenylvinyl}morpholine (cc-10b).
A mixture of chromene 3a (0.32 g, 1.0 mmol) and
α-morpholinostyrene (9) (0.19 g, 1.0 mmol) in anhydrous
MeCN (1.0 ml) was maintained for 4 h at 60°C. The
obtained solid product was filtered off and recrystallized
(
3
1
19
not observed). F NMR spectrum, δ, ppm: 85.6 (s, CF ).
3
Found, %: C 58.66; Н 4.60; N 6.21. C22
Calculated, %: C 58.67; Н 4.70; N 6.22.
H
21
F
3
N
2
O .
5
from a system of CH
white powder, mp 265–266°C (decomp.). IR spectrum,
2
Cl –hexane, 1:3. Yield 0.36 g (71%),
2
(
E)-4-Morpholino-5-[(2S*,3R*,4S*)-3-nitro-2-phenyl-
−
1
1
2
-(trifluoromethyl)chroman-4-yl]pent-3-en-2-one (ct-7). A
ν, cm : 1616, 1587, 1486, 1455, 1361. H NMR spectrum,
δ, ppm (J, Hz): 2.69–2.87 (4H, m, CH NCH ); 3.39 (1H,
OCH );
mixture of chromene 3a (0.32 g, 1.0 mmol) and (E)-4-
morpholinopent-3-en-2-one (6) (0.17 g, 1.0 mmol) in
anhydrous MeCN (0.5 ml) was maintained for 5 h at 60°C.
The mixture was then cooled to room temperature, the
2
2
dd, J = 8.9, J = 5.4, 4-CH); 3.63–3.73 (4H, m, CH
4.27 (1H, d, J = 8.9, =CH–CPh); 5.32 (1H, d, J = 5.4,
3-CH); 7.00 (1H, td, J = 7.7, J = 1.0, H-6); 7.01–7.44 (13H,
2
2
8
20

Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
1
3
m, H-5,7,8, H Ph). C NMR spectrum, δ, ppm (J, Hz):
(1H, d, J = 9.9, NH); 4.72 (1H, dd, J = 9.9, J = 5.2, 4-СН);
6.08 (1H, d, J = 5.2, 3-СН); 6.54 (2H, d, J = 8.0, H-2,6 Ph
aniline); 6.85 (1H, t, J = 7.4, H-6); 7.04 (1H, t, J = 7.4,
H-7); 7.20–7.27 (3H, m, H-5,8, H-4 Ph aniline); 7.36 (2H,
d, J = 7.6, H-2,6 Ph); 7.45–7.60 (5H, m, H-3,4,5 Ph, H-3,5
3
5.5; 48.8; 66.7; 80.0 (q, J = 30.8, C-2); 83.5; 96.8; 116.6;
22.1; 122.4 (q, J = 285.3, CF ); 122.6; 128.0; 128.5; 128.6;
28.8; 128.9; 129.0; 129.4; 132.5; 136.3; 151.0; 156.3 (one
1
1
3
19
carbon atom was not observed). F NMR spectrum, δ, ppm:
8
4.2 (s, CF
3
). Found, %: C 65.72; Н 4.80; N 5.56.
. Calculated, %: C 65.88; Н 4.94; N 5.49.
-Nitro-4-nitromethyl-2-phenyl-2-(trifluoromethyl)chro-
mane (11). A solution of chromene 3a (0.32 g, 1.0 mmol)
in CH NO (1 ml) in the presence of K CO (15 mg,
.1 mmol) was stirred for 2 days at room temperature,
then treated with 10% HCl (5 ml), extracted with CH Cl
2×1 ml), and the organic phase was dried over Na SO
The solvent was removed and the residue was
Ph aniline). 19F NMR spectrum, δ, ppm: 84.2 (s, CF
3
).
1
C
28
H
25
F
3
N
2
O
4
Isomer tc-12c. H NMR spectrum, δ, ppm (J, Hz): 3.83
(1H, d, J = 9.9, NH); 5.49 (1H, dd, J = 9.9, J = 5.6, 4-СН);
6.12 (1H, d, J = 5.6, 3-СН); 6.78 (2H, d, J = 7.9, H-2,6 Ph
aniline); 6.91 (1H, t, J = 7.4, H-6); 7.11 (1H, t, J = 7.4,
H-7); 7.24–7.34 (3H, m, H-5,8, H-4 aniline); 7.38 (2H, d,
J = 7.6, H-2,6 Ph); 7.39–7.90 (5H, m, H-3,4,5 Ph, H-3,5 Ph
3
3
2
2
3
0
2
2
(
2
4
.
aniline). 19F NMR spectrum, δ, ppm: 87.8 (s, CF
3
). Found,
. Calculated, %:
%: C 63.56; Н 3.98; N 6.88. C22
C 63.77; Н 4.14; N 6.76.
H
17
F
3
N
2
O
3
recrystallized from a system of CH
2
Cl –hexane, 1:3, giving
2
a mixture of isomers ct-11a, cc-11b, and tc-11c in 44:38:18
X-ray structural study of compounds 3a, 5, and
10a,b. Crystals suitable for X-ray structural analysis were
obtained by slow evaporation of MeCN solutions of
compounds 3a, 5, and 10a,b. The X-ray structural analysis
was performed on an Xcalibur Eos diffractometer with
CCD-detector according to the standard procedure (МоKα
radiation, graphite monochromator, ω-scanning, 2θmax
56.44°) at 22°C. The structures were solved by direct
ratio. Yield 0.29 g (77%), white powder, mp 125–126°C.
−1
IR spectrum, ν, cm : 1557, 1493, 1453, 1373. Isomer ct-11a.
1
H NMR spectrum, δ, ppm (J, Hz): 3.16 (1H, dd, J = 14.7,
J = 10.8) and 4.08 (1H, dd, J = 14.7, J = 4.8, CH
2
); 4.12
(
(
1H, dd, J = 10.8, J = 4.8, 4-СН); 5.94 (1H, s, 3-СН); 7.05
1H, br. d, J = 8.1, H-8); 7.11 (1H, td, J = 7.9, J = 1.1,
H-6); 7.33 (1H, dd, J = 8.3, J = 0.7, H-5); 7.38 (1H, br. t,
1
9
8
J = 7.9, H-7); 7.41–7.52 (5H, m, H Ph). F NMR
method using the SHELX97 software suite. The positions
1
spectrum, δ, ppm: 85.0 (s, CF
spectrum, δ, ppm (J, Hz): 3.85 (1H, dt, J = 9.7, J = 4.7,
-СН); 4.42 (1H, dd, J = 15.4, J = 9.7) and 4.99 (1H, dd,
J = 15.4, J = 4.5, CH ); 6.06 (1H, d, J = 4.9, 3-СН); 6.92
3
). Isomer cc-11b. H NMR
of non-hydrogen atoms were independently refined in
anisotropic approximation, while hydrogen atoms were
placed in geometrically calculated positions and included
in the refinement according to "rider" model with
dependent thermal parameters. The complete X-ray
structural data set for compounds 3a, 5, and 10a,b was
deposited at the Cambridge Crystallographic Data Center
(deposits CCDC 1499968, CCDC 1499970, CCDC
1499971, and CCDC 1499969, respectively).
4
2
(
1H, br. d, J = 8.0, H-8); 7.04 (1H, td, J = 7.9, J = 1.1,
H-6); 7.30 (1H, dd, J = 8.2, J = 1.0, H-5); 7.41–7.52 (5H,
m, H Ph); the signal of H-7 proton overlapped with the
1
9
corresponding signal of the major isomer. F NMR
1
spectrum, δ, ppm: 84.6 (s, CF
spectrum, δ, ppm (J, Hz): 4.48 (1H, dd, J = 15.4, J = 9.0)
and 5.14 (1H, dd, J = 15.4, J = 5.0, CH ); 4.58 (1H, dt,
3
). Isomer tc-11c. H NMR
2
The work was financially supported by the government
of the Russian Federation (program 211, contract No.
02.A03.21.0006).
J = 9.0, J = 5.1, 4-СН); 6.04 (1H, d, J = 5.1, 3-СН); 7.07
(
(
1H, br. d, J = 7.9, H-8); 7.10 (1H, br. t, J = 7.9, H-6); 7.29
1H, dd, J = 8.2, J = 1.0, H-5); 7.41–7.52 (5H, m, H Ph);
References
the signal of H-7 proton overlapped with the corresponding
1
9
1
. Korotaev, V. Yu.; Sosnovskikh, V. Ya.; Barkov, A. Yu. Russ.
Chem. Rev. 2013, 82, 1081. [Usp. Khim. 2013, 82, 1081.]
. (a) Schweizer, E. E.; Meeder-Nycz, D. In The Chemistry of
Heterocyclic Compounds: Chromenes, Chromanones, and
Chromones; Ellis, G. P., Ed.; John Wiley & Sons: New York,
signal of the major isomer. F NMR spectrum, δ, ppm:
8.0 (s, CF ). Found, %: C 53.39; Н 3.52; N 7.30.
. Calculated, %: C 53.41; Н 3.43; N 7.33.
2S*,3R*,4R*)-3-Nitro-N,2-diphenyl-2-(trifluorome-
thyl)chroman-4-amine (12). A mixture of chromene 3a
0.32 g, 1.0 mmol) and aniline (0.47 g, 5.0 mmol) was
8
C
3
2
17
(
H
13
F
3
N
2
O
5
1
977, Vol. 31, p. 11. (b) The Chemistry of Heterocyclic
(
Compounds: Chromans and Tocopherols; Ellis, G. P.;
Lockhart, I. M., Eds.; John Wiley & Sons: New York, 1981,
Vol. 36. (c) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
Chem. Rev. 2003, 103, 893. (d) Costa, M.; Dias, T. A.; Brito, A.;
Proença, F. Eur. J. Med. Chem. 2016, 123, 487.
. (a) Korotaev, V. Yu.; Sosnovskikh, V. Ya.; Kutyashev. I. B.;
Kodess, M. I. Russ. Chem. Bull., Int. Ed. 2006, 55, 317. [Izv.
Akad. Nauk, Ser. Khim. 2006, 309.] (b) Korotaev, V. Yu.;
Sosnovskikh, V. Ya.; Kutyashev. I. B.; Kodess, M. I. Russ.
Chem. Bull., Int. Ed. 2006, 55, 2020. [Izv. Akad. Nauk, Ser.
Khim. 2006, 1945.] (c) Korotaev, V. Yu.; Barkov, A. Yu.;
Kutyashev, I. B.; Kotovich, I. V.; Ezhikova, M. A.;
Kodess, M. I.; Sosnovskikh, V. Ya. Tetrahedron 2015, 71,
2658. (d) Korotaev, V. Yu.; Kutyashev, I. B.; Barkov, A. Yu.;
Sosnovskikh, V. Ya. Chem. Heterocycl. Compd. 2015, 51, 440.
[Khim. Geterotsikl. Soedin. 2015, 51, 440.] (e) Korotaev, V. Yu.;
maintained for 2 h at 100°С, then cooled to room
temperature. The excess of aniline was removed at reduced
pressure, the residue was washed with water (2×5 ml) and
dried. Recrystallization from a system of CH
:3, provided a mixture of isomers ct-12a, cc-12b, and
tc-12c in 9:36:55 ratio. Yield 0.15 g (37%), white powder,
2
Cl
2
–hexane,
3
1
−
1
mp 129–130°C. IR spectrum, ν, cm : 3388, 1604, 1591,
562, 1513, 1491, 1453, 1364, 1330. Isomer ct-12a.
1
1
H NMR spectrum, δ, ppm (J, Hz): 4.69 (1H, d, J = 10.4,
4
6
-CH); 4.95 (1H, d, J = 10.4, NH); 5.94 (1H, s, 3-CH);
.31 (2H, d, J = 8.0, H-2,6 Ph aniline); the aromatic proton
signals overlapped with the corresponding signals of the
major isomer. 19F NMR spectrum, δ, ppm: 84.6 (s, CF
).
3
1
Isomer cc-12b. H NMR spectrum, δ, ppm (J, Hz): 3.82
8
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Chemistry of Heterocyclic Compounds 2016, 52(10), 814–822
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