Synthesis and some properties of 2-(polyfluoroalkyl)chroman-4-ols and 2-(polyfluoroalkyl)chroman-4-ones

Article abstract of DOI:10.1007/s11172-009-0345-3

Reduction of 2-(polyfluoroalkyl)chromones by sodium borohydride in methanol gives cis-2-(polyfluoroalkyl)chroman-4-ols in high yields, which are easily oxidized by chromic acid to 2-(polyfluoroalkyl)chroman-4-ones. The latter are of interest as the starti

Full text of DOI:10.1007/s11172-009-0345-3

Russian Chemical Bulletin, International Edition, Vol. 58, No. 12, pp. 2465—2473, December, 2009
2465
Synthesis and some properties of 2ꢀ(polyfluoroalkyl)chromanꢀ4ꢀols
and 2ꢀ(polyfluoroalkyl)chromanꢀ4ꢀones
V. Ya. Sosnovskikh, R. A. Irgashev, and B. I. Usachev
A. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vyacheslav.Sosnovskikh@usu.ru
Reduction of 2ꢀ(polyfluoroalkyl)chromones by sodium borohydride in methanol gives
cisꢀ2ꢀ(polyfluoroalkyl)chromanꢀ4ꢀols in high yields, which are easily oxidized by chromic acid
to 2ꢀ(polyfluoroalkyl)chromanꢀ4ꢀones. The latter are of interest as the starting materials for
the preparation of novel RFꢀcontaining chromane derivatives.
Key words: chromanꢀ4ꢀones, chromanꢀ4ꢀols, reduction, oxidation, hydrazones, azines,
oximes, enones and aminoenones.
Chromane (3,4ꢀdihydroꢀ2Hꢀ1ꢀbenzopyrane) and its
derivatives are classified as important oxygenꢀcontaining
heterocycles, which are widely spread in plant world1 and
exhibit diverse types of biological activity.2 The chromane
system is an important structural fragment of many bioꢀ
logically active molecules, such as cannabinoids3 and
pterocarpans,4 and is used for the synthesis of a whole
series of condensed heterocycles.5,6 At the same time, the
synthesis of RFꢀcontaining heterocyclic compounds evoke
considerable interest in recent years, because many
of them found use as agrochemical and medical materiꢀ
als.7 However, there are few data that chromenes and
chromanes with different oxidation states (chromanols,
chromanones) bearing one or two polyfluoroalkyl groups
at the C(2) atom are used as substrates for organic syntheꢀ
sis. We have recently described the reaction of 2ꢀpolyꢀ
fluoroalkylchromones, mainly, 2ꢀtrifluoromethylchromꢀ
ones, with CF3SiMe3, which proceeds as a nucleophilic
1,4ꢀaddition of the CF3 group and gives 2,2ꢀbis(trifluoroꢀ
methyl)chromanꢀ4ꢀones with high regioselectivity.8,9 The
reduction of these compounds followed by dehydration
afforded 2,2ꢀbis(trifluoromethyl)chromenes, which are
partially fluorinated analogs of natural 2,2ꢀdimethylꢀ
chromenes and are of interest as starting materials for the
synthesis of more complicated fluorineꢀcontaining heteroꢀ
cycles with potential biological activity.9 The conjugated
trifluoromethylation of unsubstituted chromone produced
2ꢀtrifluoromethylchromanꢀ4ꢀone in low yield (30%).10
Literature data on chromanꢀ4ꢀols bearing one polyfluoroꢀ
alkyl group as substituent in position 2 are lacking.
it was expected, they turned out to be highly reactive and
promising RFꢀcontaining substrates for further functionꢀ
alization of the chromane system.
Results and Discussion
It is known that the reduction of chromones and flaꢀ
vones to the corresponding chromanols and flavanols is
more difficult than that of their dihydro derivatives, i.e.,
chromanones, and flavanones. In some cases, these reacꢀ
tions require special conditions to occur. For instance,
due to the conjugation of the phenyl group with the enone
system, flavones are resistant to NaBH4, but give cisꢀ
flavanols in good yields under the action of NiCl2/NaBH4
in methanol.11 The selective reduction of the С=С bond
in chromones and flavones was carried out only under
the action of diisobutylaluminium hydride12 and the
HCO2NH4/Pd—C system in methanol.13
We found that 2ꢀRFꢀchromones 1a—e, obtained by the
condensation of 2ꢀhydroxy and 2ꢀhydroxyꢀ4ꢀmethoxyꢀ
acetophenones with ethyl polyfluoroalkanoates,14 are
readily reduced by NaBH4 in methanol to 2ꢀRFꢀchromanꢀ
4ꢀols 2a—e (5—20 °C, 0.5 h, 65—90% yields). For loads
of chromone 1a higher than 0.2 mole, the reaction was
carried out in ethanol first at 5—20 °C and then on heatꢀ
ing (Experimental). After recrystallization from hexane
or heptane, chromanols 2 were obtained as one cisꢀisoꢀ
mer with the equatorial arrangement of the substituents,
which can be concluded on the basis of high spinꢀspin
coupling (SSC) constants (JH(3),H(2) = 11.5—12.6 Hz,
JH(3),H(4) = 9.6—11.5 Hz) characteristic of axial hydrogen
atoms in the halfꢀchair conformation15 (Scheme 1).
Taking into account the electronꢀwithdrawing charꢀ
acter of the RF group that increases the electrophilicity of
In the present work, we describe the reduction of
2ꢀRFꢀchromones to 2ꢀRFꢀchromanꢀ4ꢀols, the oxidation
of the latter to 2ꢀRFꢀchromanꢀ4ꢀones, and some properꢀ
ties of these simple but earlier unstudied compounds. As
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2386—2394, December, 2009.
1066ꢀ5285/09/5812ꢀ2465 © 2009 Springer Science+Business Media, Inc.

2466
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009
Sosnovskikh et al.
Scheme 1
impeded by the oxidative dimerization of the intermediate
thiol, which affords a mixture of cisꢀ2ꢀtrifluoromethylꢀ
chromaneꢀ4ꢀthiol 2h and bis(2ꢀtrifluoromethylchromanꢀ
4ꢀyl) disulfide 2i, which were separated by simple recrysꢀ
tallization from hexane (compound 2h has very unpleasant
and stable odor). Interestingly, disulfide 2i was the single
product that was isolated in 23% yield from the reaction
mixture of 3ꢀchloroꢀ2ꢀtrifluoromethylꢀ4Нꢀchromeneꢀ
4ꢀthione 1i (see Ref. 17) with sodium borohydride
(Scheme 3).
Scheme 3
1
a
b
c
d
e
RF
CF3
(CF2)2H
CF2H
C2F5
R
H
H
H
H
2
a
b
c
d
e
Yield (%)
83
73
70
65
90
C2F5
MeO
the C(2) atom and assists the nucleophilic 1,4ꢀaddition,14
one may suggest that the reaction proceeds via conjugated
hydrogenation through the step of formation of the enol
form of chromanone 3, which is reduced to chromanol 2
with a higher rate than the initial chromone 1. The high
stereoselectivity of the process is related, most likely, to
the fact that the borohydride anion approaches the carbonyl
group of chromanone 3 from the sterically less hindered
side, i.e., opposite to that in which the polyfluoroalkyl
group is arranged.
As chromanols 2a—g described above, chromanethiol
2h has cisꢀconfiguration (JH(3),H(2) ≈ JH(3),H(4) = 12.0 Hz),
which is retained in disulfide 2i; the Н NMR spectrum
of the latter contains one set of signals corresponding to
the mesoꢀform or a racemic mixture.
1
A similar reaction with 7ꢀperfluoroalkylnorkhellins 1f,g
(Ref. 16) afforded the corresponding cisꢀfurochromanols
2f,g (JH(3),H(2) = 11.7—12.4 Hz, JH(3),H(4) = 9.6—10.1 Hz)
in 75—80% yields (Scheme 2). Note that furochromanol
with two CF3 groups in position 7 has been synthesized
previously from 7ꢀtrifluoromethylnorkhellin 1f and (triꢀ
fluoromethyl)trimethylsilane followed by the reduction
of the furochromanone formed by sodium borohydride.9
Under the same conditions, the reduction of 2ꢀtriꢀ
fluoromethylꢀ4Нꢀchromeneꢀ4ꢀthione 1h (see Ref. 17) is
The conditions used for the reduction of 2ꢀRFꢀchromꢀ
ones (MeOH, 5—20 °C) turned out to be also appropriate
for 2ꢀtrichloromethylꢀ7ꢀmethoxychromone 1j (see Ref. 18).
However, in this case, along with pyrone ring reduction, a
secondary reaction is observed: the reduction of the
trichloromethyl group to the dichloromethyl group (most
likely, through the step of dehydrochlorination of the
preliminarily formed chromanone 3j to chromone 1k),
due to which the major reaction product, viz., cisꢀ2ꢀtriꢀ
chloromethylꢀ7ꢀmethoxychromanꢀ4ꢀol (2j) (85% yield),
contained 5% cisꢀ2ꢀdichloromethylꢀ7ꢀmethoxychromanꢀ
4ꢀol (2k) as an impurity (doublet of the proton of the
CHCl2 group at δ 6.01, J = 5.3 Hz) (Scheme 4).
Scheme 2
At first an attempt of selective reduction of the С=С
bond in chromone 1а, which is equivalent to the cessaꢀ
tion of the reaction at the step of chromanone 3 (see
Scheme 1), using diisobutylaluminium hydride was unꢀ
successful. The reaction in toluene at –70 → 20 °C for 2 h
with an excess of diisobutylaluminium hydride afforded a
1
crystalline product, which, according to the Н NMR
spectral data, was a mixture of 2ꢀtrifluoromethylꢀ4Hꢀ
chromenꢀ4ꢀol (4) (72%), 2ꢀtrifluoromethylꢀ2Hꢀchromenꢀ
RF = CF3 (f), C2F5 (g)

2ꢀ(Polyfluoroalkyl)chromanꢀ4ꢀols and ꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2467
Scheme 4
ment of toluene by THF made it possible to obtain
chromanone 3а as the single product in 56% yield. Thus,
in the case of such a bulky substituent as diisobutylꢀ
aluminium hydride, the carbonyl carbon atom is the most
accessible in a toluene solution, due to which the hydroꢀ
genation of the С=О group (products 4 and 5) becomes
the main direction of the reaction. This process is very
rarely met in the chromone series.20 The selective reducꢀ
tion of chromone 1а to chromanone 3а can be carried out
only in a THF—toluene mixture, which is associated,
most likely, with the solvating ability of THF and has
been observed earlier in the case of isoflavonones, which
gave isoflavanꢀ4ꢀones under analogous conditions.12
2ꢀTrifluoromethylꢀ2Hꢀchromene 6 was obtained in
70% yield by the reflux of chromanol 2а in benzene with
the Dean—Stark trap in the presence of pꢀtoluenesulfonic
acid followed by the treatment of the reaction mixture
with KOH and distillation in vacuo. This compound tends
to be oxidized by air oxygen, which is indicated by
the appearance of impurities of 2ꢀtrifluoromethylꢀ2Hꢀ
chromenꢀ2ꢀol 5 (6%) and 3,4ꢀepoxyꢀ2ꢀtrifluoromethylꢀ
chromane 7 (6%) in pure sample 6b after 2 months of
storage in a refrigerator. The 1Н NMR spectrum
of epoxychromane 7 exhibited the characteristic signals
of protons in positions 2—4 (CDCl3), δ: 3.91 (ddq, 1 H,
RCl = CCl3 (j), CCl H (k)
2
2ꢀol (5) (9%), and 2ꢀtrifluoromethylchromanꢀ4ꢀol (2а)
(19%) (Scheme 5). 2HꢀChromenꢀ2ꢀol 5 has recently19
been synthesized by the intramolecular cyclization of
3ꢀtrifluoromethylꢀ3ꢀphenoxypropenal in the presence
of AlCl3 through the step of formation of 4Hꢀchromenꢀ
4ꢀol 4, which, under these conditions, immediately
undergoes allyl rearrangement to more stable product 5.
4
H(3), J = 4.1 Hz, J = 1.0 Hz, JH,F = 0.6 Hz); 3.98 (d,
1 H, H(4), J = 4.1 Hz); 4.92 (qd, 1 H, H(2), 3JH,F = 7.3 Hz,
J = 1.0 Hz) (Scheme 6). The product of dehydration of
chromanol 2b turned out to be less stable and was rapidly
polymerized upon distillation in vacuo.
Scheme 6
Scheme 5
We also found that the oxidation of chromanols 2a—c
with chromic acid under heterogeneous conditions
(diethyl ether—water) at room temperature21 affords
2ꢀRFꢀchromanones 3a—c in 59—79% yields, of which
only chromanone 3а has been described earlier.10 The
structures of compounds 3a—c agree well with the data of
elemental analysis, IR spectroscopy, and 1Н and 19F NMR
spectroscopy (Scheme 7).
i. –70—20 °C; ii. –78 °C.
Using an equimolar amount of diisobutylaluminium
hydride at –78 °C, including the decomposition step, a
crystalline mixture was isolated, which consisted of alcoꢀ
hol 4 (1,2ꢀhydrogenation) and chromanone 3а (1,4ꢀhyꢀ
drogenation) in a ratio of 3 : 1, while the partial replaceꢀ
The study of the chemical properties of these comꢀ
pounds using 2ꢀRFꢀchromanones 3a,b as an example

2468
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009
Sosnovskikh et al.
Scheme 7
reaction with chromanone 3а affords 3ꢀbromoꢀ2ꢀtrifluoroꢀ
methylchromanꢀ4ꢀone 12 as a mixture of the transꢀ and
cisꢀisomers in a ratio of 94 : 6, respectively. The low SSC
constant in the major isomer (JН(2),Н(3) = 1.8 Hz) indiꢀ
cates the conformer in which the H(2) and H(3) atoms
occupy the equatorial position, which allows us to ascribe
it the transꢀconfiguration with diaxial substituents. In
the minor isomer, the value JН(2),Н(3) = 2.8 Hz is conꢀ
sistent with the cisꢀconfiguration and the conformation of
a distorted halfꢀchair. The bromination of chromanone
3а in acetic acid occurs in a low yield (29%) and affords
a mixture of transꢀ and cisꢀisomers of monobromo deriꢀ
vative 12 with 3,3ꢀdibromoꢀ2ꢀtrifluoromethylchromanꢀ
4ꢀone in a ratio of 77 : 16 : 7, respectively. An attempt to
obtain 2ꢀtrifluoromethylꢀ3ꢀnitrochromanꢀ4ꢀone by the
treatment of an acetic acid solution of 3а with acetic
anhydride and fuming nitric acid gave the starting
chromanone 3а. The condensation of 3a with benzꢀ
aldehyde in ethanol saturated with HCl resulted in
the formation of (E)ꢀ3ꢀbenzylidenechromanone 13 (the
exoꢀmethylenic proton is deshielded by the carbonyl group
RF = CF3 (a), (CF2)2H (b), CF2H (c)
showed that they are highly reactive substances, which
easily react at both the carbonyl carbon atom and
αꢀmethylene group. The reaction of chromanones 3a,b
with hydroxylamine on reflux in ethanol gives oximes
8a,b (68—75% yields). Hydrazones 9a,b were obtained
by the reaction with hydrazine hydrate under analogous
conditions in almost quantitative yield. In boiling
acetone they are transformed into nonsymmetric azines
10a,b. The treatment of hydrazone 9а with triethyl borate
and hydrochloric acid affords symmetric azine 11 in 66%
yield as a mixture of two diastereomers in a ratio of 58 : 42
(Scheme 8). It should be mentioned that azine 11 cannot
be obtained yet in appropriate yield directly from chromꢀ
anone 3а and hydrazine hydrate (2 : 1) on reflux in ethaꢀ
nol or on heating the reactants to 90 °С without a solvent.
It is unclear so far why the presence of the CF3 group
in chromanone 3а negatively affects its interaction
with N,Nꢀdimethylhydrazine and phenylhydrazine, due
to which all attempts to synthesize the corresponding
hydrazones under standard conditions, i.e., on reflux in
ethanol, were unsuccessful.
1
and appears in the Н NMR spectrum in CDCl3 as a
lowꢀfield singlet at 8.15), whereas the reflux of chromꢀ
anones 3а,b in an excess of dimethylformamide dimethylꢀ
acetal (3.5 equiv.) gives (E)ꢀ3ꢀdimethylaminomethylidene
derivatives 14a,b (δ=СН = 7.85—7.91 in CDCl3) (see
Scheme 8).
Aminoenone 14а reacts readily in transamination with
aniline and anisidine and affords compounds 15a,b, which
have the Zꢀconfiguration of the double bond due to intraꢀ
1
molecular hydrogen bonding (in the Н NMR spectrum
of aminoenone 15а in CDCl3 the exoꢀmethylenic and
NH protons appear as doublets with J = 13.0 Hz at 7.43
and 12.19, respectively). In polar DMSOꢀd6 compounds
Unlike 2ꢀunsubstituted chromanones and 2,2ꢀdiꢀ
methylchromanones, which are brominated with bromine
in CCl4 to the 3,3ꢀdibromo derivatives,22,23 a similar
Scheme 8
Rf = CF3 (a), (CF2)2H (b)

2ꢀ(Polyfluoroalkyl)chromanꢀ4ꢀols and ꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2469
off and recrystallized from heptane. The yield was 83%, colorless
15a,b exist as an equilibrium mixture of Zꢀ and Eꢀisomers
in a ratio of 4 : 1 (for Zꢀ15a δNH = 12.87, J = 12.8 Hz; for
Eꢀ15a δNH = 10.01, J = 14.2 Hz) (Scheme 9).
crystals, m.p. 127—128 °C. Found (%): C, 54.96; H, 4.18.
C10H9F3O2. Calculated (%): C, 55.05; H, 4.16. IR, ν/cm–1
3462, 1613, 1581, 1488, 1462. Н NMR (CDCl3), δ: 1.93 (d,
:
1
1 H, OH, J = 8.4 Hz); 2.03 (ddd, 1 H, Hax(3), JH
=
(3),H (3)
ax
= 12.9 Hz, JH
(2) = 12.1 Hz, JH
(4) = 10.8 Hze)q; 2.53
(3),H
ax
Scheme 9
(3),H
ax
ax
ax
(ddd, 1 H, Heq(3), JH
(3) = 12.9 Hz, JH
(4) = 6.2 Hz,
(3),H
ax
(3),H
eq
eq
JH
= 2.3 Hz); 4.e5q0 (dqd, 1 H, Hax(2), JH
=
(3),H (2)
(2),H (3)
eq
ax
ax
ax
= 12.1 Hz, JH
3 = 6.0 Hz, JH
(3) = 2.3 Hz); 5.01 (m,
(2),H
eq
(2),CF
1 H, Hax(4)); a6x.91 (dd, 1 H, H(8),aJx = 8.2 Hz, J = 1.1 Hz); 7.03
(td, 1 H, H(6), J = 7.5 Hz, J = 1.1 Hz); 7.22 (dddd, 1 H, H(7),
J = 8.2 Hz, J = 7.3 Hz, J = 1.6 Hz, 6JH(7),H (4) = 0.7 Hz); 7.49 (dt,
1 H, H(5), J = 7.7 Hz, J = 1.2 Hz). 19F NMR (CDCl3), δ: 82.82
(d, CF3, J = 6.0 Hz).
ax
Synthesis of cisꢀ2ꢀpolyfluoroalkylchromanꢀ4ꢀols (2a—g)
(general procedure). Powdered sodium borohydride (285 mg,
7.5 mmol) was added by portions to a solution of chromone 1
(5.0 mmol) in MeOH (5 mL) with stirring and cooling to 5 °С
for 0.5 h and diluted with water (10 mL). A colorless precipitate
that formed was filtered off, washed with water, dried, and
recrystallized from hexane or a mixture of heptane with diethyl
ether (5 : 1).
cisꢀ2ꢀ(1,1,2,2ꢀTetrafluoroethyl)chromanꢀ4ꢀol (2b). The
yield was 73%, colorless crystals, m.p. 101—102 °C. Found (%):
C, 52.80; H, 4.01. C11H10F4O2. Calculated (%): C, 52.81;
1
H, 4.03. IR, ν/cm–1: 3330, 1613, 1587, 1489, 1460. Н NMR
Ar = Ph (a), 4ꢀMeOC6H4 (b)
(CDCl3), δ: 2.00 (d, 1 H, OH, J = 8.4 Hz); 2.07 (dt, 1 H, H(3a),
JH
(3) = 12.8 Hz, JH
(2) = JH
(3) = 12.8 Hz, JH
(4) = 11.5); 2.51
(4) = 6.2 Hz,
(3),H
ax
Note that due to the enone moiety chromanones
13—15, whose nonꢀfluorinated analogs have been known
long ago,24,25 are interesting for the synthesis of more
complicated condensed heterocyclic compounds, includꢀ
ing partially fluorinated heteroanalogs of cannabinoids.26,27
Thus, we synthesized for the first time 2ꢀpolyfluoroꢀ
alkylchromanꢀ4ꢀols and 2ꢀpolyfluoroalkylchromanꢀ
4ꢀones, which are simple in structure but, nevertheless,
poorly studied and can be find use for subsequent synꢀ
theses of related RFꢀcontaining heterocycles. The
present preliminary study of the chemical properties of
2ꢀRFꢀchromanones confirms this assumption.
(3),H
(3),H
(3),H
ax
eq
ax
ax
ax
ax
(ddd, 1 H, Heq(3), JH
(3),H
eq
ax
eq
JH
= 1.7 Hz); 4.48—4.58 (m, 1 H, Hax(2)); 5.00 (dt,
(3),H (2)
eq
ax
1 H, Hax(4), JH
(3) = 10.7 Hz, JH
(3) = JH
=
(4),H
(4),H
(4),OH
= 7.5 Hz); 6.16 (tdd, 1 H, CF2CF2H, 2JH,F = 53.3eHq z, 3JH,F = 4.4 Hz,
JH,F = 7.0 Hz); 6.82 (dd, 1 H, H(8), J = 8.2 Hz, J = 1.0 Hz);
7.02 (td, 1 H, H(6), J = 7.5, 1.0 Hz); 7.21 (ddd, 1 H, H(7),
J = 8.2 Hz, J = 7.3 Hz, J = 1.5 Hz); 7.49 (br.d, 1 H, H(5),
J = 7.7 Hz). 19F NMR (CDCl3), δ: 18.00 (ddt, CFFH,
2JF,F = 301.6 Hz, 2JF,H = 53.7 Hz, 3JF,F = 8.8 Hz); 24.97 (dddd,
ax
ax
ax
ax
2
2
3
CFFH, JF,F = 301.6 Hz, JF,H = 52.7 Hz, JF,F = 6.0 Hz,
3JF,F = 2.3 Hz); 30.00—30.13 (m, CF2).
cisꢀ2ꢀDifluoromethylchromanꢀ4ꢀol (2c). The yield was 70%,
colorless crystals, m.p. 79—80 °C. Found (%): C, 59.84; H, 4.90.
C10H10F2O2. Calculated (%): C, 60.00; H, 5.04. IR, ν/cm–1
:
1
Experimental
3445, 1613, 1581, 1487, 1461. Н NMR (CDCl3), δ: 1.70 (br.s,
1 H, OH); 2.05 (dt, 1 H, Hax(3), JH
= 13.4 Hz,
(3),H (3)
ax
= 9.5 Hz); 2.43 (dedqd, 1 H, Heq(3),
IR spectra were obtained on a FTꢀIR Nicolet 6700 instruꢀ
JH
= JH
(3),H (2)
(3),H (4)
ax
ax
ax
ax
1
ment in KBr pellets. Н and 19F NMR spectra were recorded
JH
= 13.4 Hz, JH
= 5.7 Hz, JH
(3),H (2)
eq ax
=
=
(3),H (3)
(3),H (4)
eq
ax
ax
= 3.0 Hz); 4.37 (qdd, 1 H, eHq ax(2), JH
= JH
on a Bruker DRXꢀ400 spectrometer in CDCl3 at working
frequencies of 400.1 MHz (1Н) and 376.5 MHz (19F), using
Me4Si and C6F6 as internal standards. The starting chromones
1a—j were synthesized by known procedures,16—18,28 and other
reactants are commercial.
(2),H (3)
(2),CF
ax
ax
2
9.9 Hz, JH
2 = 4.5 Hz, JH
(3) = 3.0 Hz);ax4.98 (dd,
(2),CHF
(2),H
eq
1 H, Hax(4a)x, JH
(3) = 8.9 Hazx, JH
(3) = 5.7 Hz); 5.99
(4),H
(4),H
eq
(ddd, 1 H, CHF2, JH,F = 55.2 Hz, Ja=x 55.9 Hz, J = 4.5 Hz);
ax
ax
2
6.88 (dd, 1 H, H(8), J = 8.2 Hz, J = 1.2 Hz); 7.00 (td, 1 H, H(6),
cisꢀ2ꢀTrifluoromethylchromanꢀ4ꢀol (2a). To obtain large
amounts of chromanol 2а, powdered sodium borohydride (11.3 g,
0.3 mol) was placed in a twoꢀnecked flask with a reflux
condenser, and ethanol (350 mL) was added with stirring. The
mixture was stirred until NaBH4 dissolved completely. Then
chromone 1а (42.2 g, 0.2 mol) was added by portions with
cooling to 5 °С and continuous stirring. The resulting mixture
was refluxed for 3 h, and a 50% solution of acetic acid (36 mL)
and water (200 mL, to dissolve the boric acid precipitated) were
added dropwise. After the alcohol was distilled off in a vacuum
of a waterꢀjet pump, a precipitate of chromanol 2а was filtered
J = 7.5 Hz, J = 1.2 Hz); 7.22 (dddd, 1 H, H(7), J = 8.2 Hz,
6
J = 7.3 Hz, J = 1.7 Hz, JH(7),H
= 0.6 Hz); 7.43 (ddd, 1 H,
(4)
H(5), J = 7.8 Hz, J = 1.5 Hz, 4JaHx (5),H (4) = 1.0 Hz). 19F NMR
ax
(CDCl3), δ: 30.63 (ddd, CFF, 2JF,F = 291.4 Hz, 2JF,H = 55.2 Hz,
3JF,H = 10.0 Hz); 34.97 (ddd, CFF, JF,F = 291.4 Hz, JF,H
=
2
2
= 55.9 Hz, 3JF,H = 9.8 Hz).
cisꢀ2ꢀPerfluoroethylchromanꢀ4ꢀol (2d). The yield was 65%,
colorless crystals, m.p. 120—121 °C. Found (%): C, 49.00;
H, 3.28. C11H9F5O2. Calculated (%): C, 49.26; H, 3.38.
IR, ν/cm–1: 3344, 3253, 1614, 1588, 1489, 1460. 1Н NMR
(CDCl3), δ: 1.90 (d, 1 H, OH, J = 8.5 Hz); 2.10 (td, 1 H, Hax(3),

2470
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009
Sosnovskikh et al.
JH
(3) = JH
(2) = 12.6 Hz, JH (4) = 10.8 Hz);
(3),H
Found (%): C, 51.69; H, 3.56. C20H16F6O2S2. Calculated (%):
C, 51.50; H, 3.46. Н NMR (CDCl3), δ: 2.21—2.34 (m, 2 H,
(3),H
(3),H
ax
ax
2.55 (ddetq, 1 H, Heq(3),axJH
= 12a.x8 Hza,xJH
=
(3),H (3)
ax
1
(3),H (3)
ax
eq
= 6.2 Hz, JH
= eJqH
= 2.0 Hz); 4.62 (dddd,
CH2); 4.21 (dd, 1 H, H(4), J = 10.9 Hz, J = 7.3 Hz); 4.24—4.32
(m, 1 H, H(2)); 6.91 (dd, 1 H, H(8), J = 8.2 Hz, J = 1.1 Hz);
6.99 (td, 1 H, H(6), J = 7.6 Hz, J = 1.2 Hz); 7.19 (dddd, 1 H,
(3),H (2)
(3),CFF
1 H, H(2), JHeq
= 17.0 Hz, JH
= 12.0 Hz,
(2),H (3)
ax
eq
(2),CFF
ax
ax
ax
JH
Hax(4), JH
= 5.0 Hz, JH
= 2.0 Hz); 5.04 (dt, 1 H,
(2),H (3)
eq
(2),CFF
ax
ax
(3) = 10.0 Hz, JH
≈ JH (4),OH = 7.5 Hz);
(4),H (3)
eq
H(7), J = 8.2 Hz, J = 7.3 Hz, J = 1.7 Hz, 6JH(7),H (4) = 0.8 Hz);
(4),H
ax
ax
ax
ax
ax
6.88 (dd, 1 H, H(8), J = 8.2 Hz, J = 1.0 Hz); 7.03 (td, 1 H, H(6),
J = 7.5 Hz, J = 1.0 Hz); 7.22 (ddd, 1 H, H(7), J = 8.3 Hz,
J = 7.3 Hz, J = 1.3 Hz); 7.49 (dt, 1 H, H(5), J = 7.7 Hz, J = 1.0 Hz).
cisꢀ7ꢀMethoxyꢀ2ꢀperfluoroethylchromanꢀ4ꢀol (2e). The yield
was 90%, colorless crystals, m.p. 112—113 °C. Found (%):
C, 48.32; H, 3.70. C12H11F5O3. Calculated (%): C, 48.33;
7.59 (dt, 1 H, H(5), J = 7.8 Hz, J = 1.2 Hz).
cisꢀ7ꢀMethoxyꢀ2ꢀtrichloromethylchromanꢀ4ꢀol (2j) was
obtained from chromone 1j by a similar procedure. The yield
was 85%, colorless crystals, m.p. 119—120 °C (octane). Found (%):
C, 44.72; H, 3.96. C11H11Cl3O3. Calculated (%): C, 44.40;
H, 3.73. 1Н NMR (CDCl3), δ: 2j: 1.80 (d, 1 H, OH, J = 7.3 Hz);
1
H, 3.72. Н NMR (CDCl3), δ: 1.85 (d, 1 H, OH, J = 8.4 Hz);
2.05 (ddd, 1 H, Hax(3), JH
= 12.6 Hz, JH
=
(3),H (3)
(3),H(2)
ax
eq
ax
2.05 (td, 1 H, Hax(3), JH
= JH
= 12.2 Hz,
= 11.6 Hz, JH
= 11.1 Hz); 2.91 (ddd, 1 H, Heq(3),
(3),H(4)
(3),H (3)
(3),H (2)
ax
eq
ax
ax
ax
JH
= 11.0 Hz); 2.53 (ddt, 1 H, Heq(3), JH
=
=
JH
(3) = 12.6 Hz, JH (3),H(4) = 6.2 Hz, JH (3),H(2) = 2.0 Hz);
(3),H
ax eq
(3),H (4)
(3),H (3)
ax
ax
ax
eq
= 12.9 Hz, JH
= 6.3 Hz, JH
(2) = JeHq
3.79 (s, 3 H, MeO); 4.56 e(qdd, 1 H, H(2), JH(2),H (3) = 11.6 Hz,
(3),H (4)
(3),H
(3),CFF
= 2.0 Hz); 3.78 (s, 3 H, MeO); 4.54—4e.q64 (m, 1 H, H eq(2)); 4.98
JH(2),H (3) = 2.0 Hz); 5.02 (br.dt, 1 H, H(4), JH(4),H (3) = 11.1 Hz,
JH(4),H
6.61 (dd, 1 H, H(6), J = 8.6 Hz, J = 2.5 Hz); 7.39 (dd, 1 H, H(5),
J = 8.6 Hz, J = 0.9 Hz); cisꢀ2ꢀdichloromethylꢀ7ꢀmethoxyꢀ
eq
ax
ax
ax
ax
eq
(br.q, 1 H, Hax(4), J = 8.2 Hz); 6.40 (d, 1 H, H(8), J = 2.5 Hz);
6.61 (dd, 1 H, H(6), J = 8.6 Hz, J = 2.5 Hz); 7.37 (dd, 1 H,
H(5), J = 8.6 Hz, J = 0.6 Hz).
≈ JH(4),OH = 6.5 Hz); 6.51 (d, 1 H, H(8a)x, J = 2.5 Hz);
(3)
eq
cisꢀ4,9ꢀDimethoxyꢀ7ꢀtrifluoromethylꢀ6,7ꢀdihydroꢀ5Hꢀfuroꢀ
[3,2ꢀg]chromenꢀ5ꢀol (2f). The yield was 80%, colorless crystals,
m.p. 94—95 °C. Found (%): C, 52.75; H, 4.17. C14H13F3O5.
Calculated (%): C, 52.84; H, 4.12. IR, ν/cm–1: 3374, 1628,
1607, 1490. 1Н NMR (CDCl3), δ: 2.19 (ddd, 1 H, Hax(3),
chromanꢀ4ꢀol (2k) (5%): 2.19 (dt, 1 H, Hax(3), JH
=
(3),H (3)
= 13.5 Hz, JH
Heq(3), JH
= JH
= 9.2 Hz); 2.55ax(ddde,q1 H,
(3),H(4)
(3),H(2)
ax
ax
(3) = 13.5 Hz, JH (3),H(4) = 5.8 Hz, JH
(3),H(2)
eq
=
=
(3),H
= 2.9 Hz);e3q.78 (s, 3 H, MeO); 4.45 (ddd, 1 H, H(2), JH(2),H
ax
eq
(3)
ax
= 9.2 Hz, JH(2),CHCl = 5.3 Hz, JH(2),H
= 2.9 Hz); 6.01 (d,
(3)
eq
2
JH
= 13.5 Hz, JH
= 11.7 Hz, JH =
(3),H (4)
ax
1 H, CHCl2, J = 5.3 Hz); 6.44 (d, 1 H, H(8), J = 2.5 Hz);
6.58 (dd, 1 H, H(6), J = 8.6 Hz, J = 2.5 Hz); 7.33 (d, 1 H, H(5),
J = 8.6 Hz).
(3),H (3)
(3),H (2)
ax
eq
ax
ax
= 9.6 Hz); 2.55 (ddd, 1 H, Heq(3), JH
= 13.a5x Hz,
(3),H (3)
eq
ax
JH
(4) = 7.2 Hz, JH
(2) = 2.3 Hz); 4.02 (s, 3 H, MeO);
(3),H
(3),H
eq
4.15 (s, a3x H, MeO); 4.e4q2 (daqxd, 1 H, Hax(2), JH
=
2ꢀTrifluoromethylꢀ4Hꢀchromenꢀ4ꢀol (4). A 1.5 М solution
(5.0 mL) of diisobutylaluminium hydride (7.5 mmol) in toluene
was added to a solution of chromone 1а (1.0 g, 4.7 mmol) in
toluene (6 mL) with stirring and cooling to –70 °С. The reaction
mixture was stored for 2 h at ~20 °C and treated with water
(5 mL), the organic layer was separated, the solvent was distilled
off, and the residue was recrystallized from hexane. The yield
was 0.65 g, colorless product with m.p. 70—72 °С, which,
according to the 1Н NMR spectral data, was a mixture of
2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀol 4 (72%), 2ꢀtrifluoromethylꢀ
chromanꢀ4ꢀol 2а (19%), and 2ꢀtrifluoromethylꢀ2Hꢀchromenꢀ
2ꢀol 5 (9%). 1Н NMR (CDCl3), δ for 4: 2.03 (d, 1 H, OH,
J = 9.5 Hz); 5.43 (dd, 1 H, H(4), J = 9.5 Hz, J = 4.2 Hz); 5.95
(d, 1 H, H(3), J = 4.2 Hz); 7.14 (dd, 1 H, H(8), J = 8.3 Hz,
J = 1.2 Hz); 7.23 (td, 1 H, H(6), J = 7.5 Hz, J = 1.2 Hz); 7.36
(ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.53 (dd,
1 H, H(5), J = 7.7 Hz, J = 1.7 Hz); for 5: 3.37 (br.s, 1 H, OH);
5.89 (d, 1 H, H(3), J = 10.0 Hz); 6.91 (d, 1 H, H(4), J = 10.0 Hz);
7.00—7.05 (m, 2 H, H(6), H(8)); 7.29 (ddd, 1 H, H(7), J = 8.2 Hz,
J = 7.3 Hz, J = 1.7 Hz); 7.36 (dd, 1 H, H(5), J = 7.6 Hz, J = 1.7 Hz).
Synthesis of 2ꢀtrifluoromethylchromanꢀ4ꢀone (3а) from
chromone 1а. A 1.5 М solution (5.0 mL) of diisobutylaluminium
hydride (7.5 mmol) in toluene was added under argon atmosphere
to a solution of chromone (5.0 mL) in THF (30 mL) cooled to
–78 °С. The addition was carried out with such a rate that the
temperature of the mixture did not increase above –70 °С. Then
the solution was stirred for 3 h at –78 °С and decomposed with
water (5 mL) at the same temperature, after which the reaction
mixture was allowed to warm to ~20 °С, and KOH (3 g in 5 mL
of water to remove aluminum hydroxide) and ether (30 mL)
were added. The ethereal layer was separated, and the aqueous
layer was extracted with ether (10 mL). The organic extracts
were washed with a saturated solution of NaCl, the solvent was
evaporated, and the residue was dissolved in methanol, filtered,
(2),H (3)
ax
= 11.7 Hz, JH
1 H, Hax(4), JH
3 = 6.1 Hz, JH
(3) = 2.3 Hazx); 5.31 (dd,
(2),H
eq
(2),CF
ax
ax
(3) = 9.6 Hz, JH
(3) = 7.2 Hz); 6.86
(4),H
eq
(4),H
(d, 1 H, H(3), Jax= 2.3 Hz); 7.52 (d, 1 H, H(2), J = 2.3 Hz).
cisꢀ4,9ꢀDimethoxyꢀ7ꢀperfluoroethylꢀ6,7ꢀdihydroꢀ5Hꢀfuroꢀ
[3,2ꢀg]chromenꢀ5ꢀol (2g). The yield was 75%, colorless crystals,
m.p. 97—98 °C. Found (%): C, 49.00; H, 3.34. C15H13F5O5.
Calculated (%): C, 48.92; H, 3.56. IR, ν/cm–1: 3385, 1629,
1606, 1489. 1Н NMR (CDCl3), δ: 2.24 (ddd, 1 H, Hax(3),
ax
ax
JH
= 13.0 Hz, JH
= 12.4 Hz, JH
=
(3),H (3)
(3),H (2)
(3),H (4)
ax
eq
ax
ax
ax
= 10.1 Hz); 2.58 (ddt, 1 H, H (3), JH
= 13.a4x Hz,
(3),H (3)
eq
eq
JH
= 7.4 Hz, JH
= 1.8 Hza)x; 3.96 (s, 3 H,
MeO); 4.15 (s, 3 H, MeO); 4.51 (m, 1 H, Hax(2)); 5.34 (ddd,
1 H, Hax(4), JH = 9.4 Hz, JH = 7.4 Hz,
(3),H (4)
(3),H (2)
eq
ax
eq
ax
(4),H (3)
(4),H (3)
eq
ax
ax
JH
(2) = 1.3 Hz);a6x .86 (d, 1 H, H(3), J = 2.3 Hz); 7.52 (d,
(4),H
ax
ax
1 H, H(2), J = 2.3 Hz).
Thiol 2h and disulfide 2i were obtained from thione 1h using
an analogous procedure.
cisꢀ2ꢀTrifluoromethylchromaneꢀ4ꢀthiol (2h). The yield was
40%, colorless needles, m.p. 54—55 °C. Found (%): C, 51.38;
H, 3.71. C10H8F3OS. Calculated (%): C, 51.28; H, 3.87. 1Н NMR
(CDCl3), δ: 1.98 (d, 1 H, SH, J = 8.7 Hz); 2.18 (dt, 1 H, Hax(3),
JH
(3) = 13.4 Hz, JH
(2) = JH
(4) = 12.0 Hz);
(3),H
(3),H
(3),H
2.64 (ddedq, 1 H, Heq(3), JH
= 13.4 Hza,x JH
=
(3),H (4)
ax
ax
ax
ax
(3),H (3)
ax
ax
= 5.9 Hz, JH
JH
= 5.9 Hz); 4.41 (dqd, 1 H, Hax(2), JH
JH
J = 8.2 Hz, J = 1.2 Hz); 7.01 (td, 1 H, H(6), J = 7.6 Hz, J = 1.2 Hz);
7.19 (dddd, 1 H, H(7), J = 8.2 Hz, J = 7.3 Hz, J = 1.6 Hz,
6JH(7),H (4) = 0.8 Hz); 7.65 (dt, 1 H, H(5), J = 7.8 Hz, J = 1.3 Hz).
Bis(2ꢀtrifluoromethylchromanꢀ4ꢀyl) disulfide (2i). The
yield was 32% (from chromenethione 1h), 23% (from chromeneꢀ
thione 1i), colorless crystals, m.p. 159—161 °C (CCl4—hexane).
=eq2.1 Hz); 4.25 (ddd, 1 eqH, Hax(4),
(3),H (2)
eq
= 12.0axHz, JH
= 8.7 Hz, JH
=
(4),H (3)
(4),H (3)
(4),HS
ax
ax
ax
eq
a=x 11.9 Hz,
(2),H (3)
ax
ax
3 = 5.9 Hz, JH
(3) = 2.1 Hz); 6.90 (dd, 1 H, H(8),
(2),H
eq
(2),CF
ax
ax
ax

2ꢀ(Polyfluoroalkyl)chromanꢀ4ꢀols and ꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2471
1
and cooled to –30 °С. The product that precipitated was filtered
off, washed with petroleum ether, and dried. Chromanone
3а was obtained in a yield of 850 mg (56%), m.p. 85—86 °С
(Ref. 10: m.p. 84—85 °С).
1608, 1488, 1459. Н NMR (CDCl3), δ: 5.23 (qdd, 1 H, H(2),
3JH,F = 6.7 Hz, J = 3.8 Hz, J = 1.8 Hz); 5.65 (dd, 1 H, H(3),
J = 10.0 Hz, J = 3.8 Hz); 6.66 (dd, 1 H, H(4), J = 10.0 Hz,
J = 1.2 Hz); 6.86 (d, 1 H, H(8), J = 8.1 Hz); 6.91 (td, 1 H,
H(6), J = 7.4 Hz, J = 1.1 Hz); 7.01 (dd, 1 H, H(5), J = 7.5 Hz,
J = 1.7 Hz); 7.16 (td, 1 H, H(7), J = 7.6 Hz, J = 1.7 Hz).
After two months of storage in a refrigerator, oxidation
products appeared in the pure sample of chromene 6. They were
Synthesis of 2ꢀtrifluoromethylchromanꢀ4ꢀone (3а) from
chromanol 2а. A solution of Na2Cr2O7 (21.4 g, 0.082 mol) and
concentrated H2SO4 (20.0 mL) in water (120 mL) were added to
a solution of chromanol 2а (35.6 g, 0.163 mol) in diethyl ether
(350 mL) with stirring and iceꢀcooling. The obtained mixture
was stirred for 4 h at ~20 °С and then left to stay for 16 h. The
organic layer was separated, and the aqueous layer was extracted
with ether (25 mL). The combined extracts were washed with a
5% solution of soda (2Ѕ50 mL) and water (50 mL) and dried
with anhydrous calcium chloride. After the ether was distilled
off, the residue was recrystallized from hexane, and chromanone
3a was obtained in a yield of 27.8 g (79%), colorless crystals,
m.p. 85—86 °C (Ref. 10: m.p. 84—85 °С). IR, ν/cm–1: 1704,
1
identified on the basis of the Н NMR spectrum as 2ꢀtrifluoroꢀ
methylꢀ2Hꢀchromenꢀ2ꢀol (5) (6%) and 3,4ꢀepoxyꢀ2ꢀtrifluoroꢀ
methylchromane (7) (6%). 1Н NMR (CDCl3), δ for 7: 3.91
(ddq, 1 H, H(3), J = 4.13 Hz, J = 1.0 Hz, 4JH,F = 0.6 Hz); 3.98
(d, 1 H, H(4), J = 4.1 Hz); 4.92 (qd, 1 H, H(2), 3JH,F = 7.3 Hz,
J = 1.0 Hz); 7.00—7.05 (m, 2 H, H(6), H(8)); 7.18 (dd, 1 H,
H(5), J = 7.6 Hz, J = 1.7 Hz); 7.30 (ddd, 1 H, H(7), J = 8.2 Hz,
J = 7.3 Hz, J = 1.7 Hz).
2ꢀTrifluoromethylchromanꢀ4ꢀone oxime (8a). Chromanone
3a (410 mg, 1.90 mmol) was added to a solution of hydroxylamine
obtained from NH2OH•HCl (400 mg, 5.75 mmol) and KOH
(320 mg, 5.70 mmol) in ethanol (10 mL). The mixture was
refluxed for 3 h and then poured into water (40 mL), and the
crystals precipitated were filtered off and washed with water.
Oxime 8a was obtained in a yield of 300 mg as colorless crystals,
m.p. 147—148 °C. Found (%): C, 51.81; H, 3.41; N, 5.97.
C10H8F3NO2. Calculated (%): C, 51.96; H, 3.49; N, 6.06.
1
1614, 1604, 1578, 1475, 1464. Н NMR (CDCl3), δ: 2.92 (dd,
1 H, CHH, J = 16.9 Hz, J = 3.9 Hz); 3.01 (dd, 1 H, CHH,
J = 16.9 Hz, J = 12.3 Hz); 4.82 (dqd, 1 H, CH, J = 12.3 Hz,
J = 5.8 Hz, J = 3.9 Hz); 7.09 (dd, 1 H, H(8), J = 8.4 Hz, J = 1.0 Hz);
7.12 (ddd, 1 H, H(6), J = 7.9 Hz, J = 7.3 Hz, J = 1.0 Hz); 7.56
(ddd, 1 H, H(7), J = 8.4 Hz, J = 7.3 Hz, J = 1.8 Hz); 7.91 (dd,
1 H, H(5), J = 7.9 Hz, J = 1.8 Hz).
2ꢀ(1,1,2,2ꢀTetrafluoroethyl)chromanꢀ4ꢀone (3b) was
obtained similarly to chromanone 3а in 59% yield (2.5 g from
4.3 g of chromanol 2b), colorless crystals, m.p. 49—50 °C
(heptane—diethyl ether). Found (%): C, 53.09; H, 3.03. C11H8F4O2.
Calculated (%): C, 53.24; H, 3.25. IR, ν/cm–1: 1702, 1605,
IR, ν/cm–1: 3270, 1609, 1580, 1488, 1461. Н NMR (CDCl3),
1
δ: 2.76 (dd, 1 H, CHH, J = 17.2 Hz, J = 12.1 Hz); 3.54 (dd,
1 H, CHH, J = 17.2 Hz, J = 3.6 Hz); 4.46 (dqd, 1 H, CH,
J = 12.1 Hz, J = 5.9 Hz, J = 3.6 Hz); 7.00—7.06 (m, 2 H, H(8),
H(6)); 7.33 (ddd, 1 H, H(7), J = 8.2 Hz, J = 7.3 Hz, J = 1.6 Hz);
7.83 (dd, 1 H, H(5), J = 7.9 Hz, J = 1.6 Hz); 7.9—8.3 (br.s,
1 H, OH).
1
1579, 1474, 1464. Н NMR (CDCl3), δ: 2.90 (ddd, 1 H, CHH,
J = 16.9, 3.4 Hz, 4JH,F = 1.0 Hz); 3.09 (dd, 1 H, CHH, J = 16.9 Hz,
J = 12.0 Hz); 4.84—4.95 (m, 1 H, CH); 6.19 (dddd, 1 H,
2
2
3
CF2CF2H, JH,F = 53.7 Hz, JH,F = 52.3 Hz, JH,F = 9.0 Hz,
3JH,F = 1.6 Hz); 7.03 (d, 1 H, H(8), J = 8.3 Hz); 7.12 (ddd,
1 H, H(6), J = 7.9 Hz, J = 7.3 Hz, J = 1.0 Hz); 7.55 (ddd, 1 H,
H(7), J = 8.4 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.93 (dd, 1 H, H(5),
J = 7.9 Hz, J = 1.7 Hz).
2ꢀ(1,1,2,2ꢀTetrafluoroethyl)chromanꢀ4ꢀone oxime (8b)
was obtained similarly to oxime 8а in 76% yield (200 mg from
250 mg of chromanone 3b), colorless crystals, m.p. 143—144 °C.
Found (%): C, 50.33; H, 3.42; N, 5.14. C11H9F4NO2. Calculꢀ
ated (%): C, 50.20; H, 3.45; N, 5.32. IR, ν/cm–1: 3270, 1608,
1
2ꢀDifluoromethylchromanꢀ4ꢀone (3c) was obtained similarly
to chromanone 3а in 74% yield (5.9 g from 8.0 g of chromanol
2с), colorless crystals, m.p. 57—58 °C (heptane—diethyl ether).
Found (%): C, 60.60; H, 3.99. C10H8F2O2. Calculated (%):
C, 60.61; H, 4.07. IR, ν/cm–1: 1698, 1606, 1577, 1474, 1463.
1Н NMR (CDCl3), δ: 2.83 (dd, 1 H, CHH, J = 16.9 Hz,
J = 3.6 Hz); 2.94 (dd, 1 H, CHH, J = 16.9 Hz, J = 12.7 Hz);
4.82 (tdt, 1 H, CH, J = 12.7 Hz, J = 7.8 Hz, J = 3.5 Hz); 6.04
(ddd, 1 H, CHF2, 2JH,F = 55.6 Hz, 2JH,F = 54.2 Hz, J = 3.3 Hz);
7.04 (dd, 1 H, H(8), J = 8.4 Hz, J = 1.1 Hz); 7.08 (ddd,
1 H, H(6), J = 7.9 Hz, J = 7.3 Hz, J = 1.1 Hz); 7.53 (ddd,
1 H, H(7), J = 8.4 Hz, J = 7.3 Hz, J = 1.8 Hz); 7.90 (dd, 1 H,
H(5), J = 7.9 Hz, J = 1.8 Hz). 19F NMR (CDCl3), δ:
1579, 1488, 1458. Н NMR (CDCl3), δ: 2.80 (dd, 1 H, CHH,
J = 17.2 Hz, J = 12.5 Hz); 3.55 (dd, 1 H, CHH, J = 17.2 Hz,
J = 3.3 Hz); 4.45—4.56 (m, 1 H, CH); 6.19 (dddd, 1 H,
2
2
3
CF2CF2H, JH,F = 53.5 Hz, JH,F = 52.6 Hz, JH,F = 6.9 Hz,
3JH,F = 4.2 Hz); 6.95 (dd, 1 H, H(8), J = 8.3 Hz, J = 1.0 Hz);
7.04 (ddd, 1 H, H(6), J = 8.0 Hz, J = 7.2 Hz, J = 1.0 Hz); 7.32
(ddd, 1 H, H(7), J = 8.3 Hz, J = 7.2 Hz, J = 1.6 Hz); 7.84 (dd,
1 H, H(5), J = 8.0 Hz, J = 1.6 Hz); 7.9—8.6 (br.s, 1 H, OH).
2ꢀTrifluoromethylchromanꢀ4ꢀone hydrazone (9a). 60%
Hydrazine hydrate (180 mg, 3.47 mmol) was added to a solution
of chromanone 3а (300 mg, 1.39 mmol) in ethanol (5 mL). The
reaction mixture was refluxed for 4 h, then poured into water
(30 mL), and left to stay for 16 h, allowing the alcohol to
evaporate. The crystals precipitated were filtered off and washed
with water. Hydrazone 9a was obtained in a yield of 310 mg
(97%), colorless crystals, m.p. 78—80 °C. Found (%): C, 52.17;
H, 3.72; N, 12.32. C10H9F3N2O. Calculated (%): C, 52.18;
H, 3.94; N, 12.17. IR, ν/cm–1: 3383, 3327, 3236, 1653, 1613,
2
2
3
29.82 (ddd, CFF, JF,F = 294.9 Hz, JF,H = 55.6 Hz, JF,H
=
2
2
12.7 Hz); 33.26 (ddd, CFF, JF,F = 294.9 Hz, JF,H = 54.2 Hz,
3JF,H = 7.8 Hz).
2ꢀTrifluoromethylꢀ2Hꢀchromene (6). A solution of chromanol
2a (5.5 g, 0.025 mol) in benzene (50 mL) was refluxed for 5 h
with the Dean—Stark trap in the presence of the catalytic amount
of pꢀtoluenesulfonic acid. Then the reaction mixture was washed
with a 40% solution of KOH, dried above KOH, benzene was
distilled off, and the residue was distilled, collecting the fraction
with b.p. 80—81 °С at 15 Torr, colorless liquid. The yield was
3.5 g (70%). Found (%): C, 59.75; H, 3.32. C10H7F3O. Calculꢀ
ated (%): C, 60.01; H, 3.53. IR (thin layer), ν/cm–1: 1650,
1
1572, 1482, 1459. Н NMR (CDCl3), δ: 2.54 (dd, 1 H, CHH,
J = 16.2 Hz, J = 12.1 Hz); 3.04 (dd, 1 H, CHH, J = 16.2 Hz,
J = 3.5 Hz); 4.46 (dqd, 1 H, CH, J = 12.1 Hz, J = 5.9 Hz,
J = 3.5 Hz); 5.38 (br.s, 2 H, NH2); 6.98 (dd, 1 H, H(8), J = 8.3 Hz,
J = 0.9 Hz); 7.02 (ddd, 1 H, H(6), J = 7.9 Hz, J = 7.3 Hz,
J = 1.2 Hz); 7.24 (ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz,
J = 1.7 Hz); 7.89 (dd, 1 H, H(5), J = 7.9 Hz, J = 1.7 Hz).

2472
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009
Sosnovskikh et al.
2ꢀ(1,1,2,2ꢀTetrafluoroethyl)chromanꢀ4ꢀone hydrazone (9b)
was synthesized similarly to hydrazone 9а in 91% yield (240 mg
from 250 mg of chromanone 3b), m.p. 115—116 °C. Found (%):
C, 50.26; H, 3.71; N, 10.44. C11H10F4N2O. Calculated (%):
C, 50.39; H, 3.84; N, 10.68. IR, ν/cm–1: 3367, 3307, 3230,
H(5), J = 7.9 Hz, J = 1.6 Hz); (minor isomer, 42%) 3.02 (dd,
1 H, CHH, J = 17.1 Hz, J = 10.9 Hz); 3.56 (dd, 1 H, CHH,
J = 17.1 Hz, J = 4.0 Hz); 5.17—5.27 (m, 1 H, CH); 7.11 (dd, 1 H,
H(8), J = 8.3 Hz, J = 1.1 Hz); 7.16 (ddd, 1 H, H(6), J = 7.9 Hz,
J = 7.3 Hz, J = 1.1 Hz); 7.48 (ddd, 1 H, H(7), J = 8.3 Hz,
J = 7.3 Hz, J = 1.6 Hz); 8.14 (dd, 1 H, H(5), J = 7.9 Hz, J = 1.6 Hz).
3ꢀBromoꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (12). A solution
of bromine (670 mg, 4.17 mmol) in CCl4 (2 mL) was added
to a solution of chromanone 3а (300 mg, 1.39 mmol) in CCl4
(5 mL). The reaction mixture was stored for 1 day at ~20 °С,
after which it was washed with water (20 mL) and a 10% solution
of sodium sulfite (20 mL). The organic phase was dried with
calcium chloride, the solvent was distilled off in vacuo, and the
residue was recrystallized from hexane. Product 12 was obtained
in a yield of 220 mg (54%) as a mixture of two isomers transꢀ12
and cisꢀ12 in a ratio of 94 : 6, colorless crystals, m.p. 94—96 °C.
Found (%): C, 40.65; H, 2.07. C10H6BrF3O2. Calculated (%):
C, 40.71; H, 2.05. IR, ν/cm–1: 1687, 1606, 1582, 1476, 1464.
1Н NMR (CDCl3), δ for transꢀ12: 4.60 (d, 1 H, H(3), J = 1.8 Hz);
4.77 (qd, 1 H, H(2), J = 5.6 Hz, J = 1.8 Hz); 7.18 (dd, 1 H,
H(8), J = 8.3 Hz, J = 1.0 Hz); 7.21 (ddd, 1 H, H(6), J = 7.9 Hz,
J = 7.3 Hz, J = 1.1 Hz); 7.63 (ddd, 1 H, H(7), J = 8.4 Hz,
J = 7.3 Hz, J = 1.7 Hz); 7.98 (dd, 1 H, H(5), J = 7.9 Hz, J = 1.7 Hz);
for cisꢀ12: 4.69 (d, 1 H, H(3), J = 2.8 Hz); 5.01 (qd, 1 H,
H(2), J = 7.0 Hz, J = 2.8 Hz); 7.11 (d, 1 H, H(8), J = 8.3 Hz);
7.16 (td, 1 H, H(6), J = 7.6 Hz, J = 1.0 Hz); 7.61 (ddd, 1 H,
H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.93 (dd, 1 H, H(5),
J = 7.9 Hz, J = 1.7 Hz).
1
1647, 1616, 1575, 1482, 1459. Н NMR (CDCl3), δ: 2.62 (dd,
1 H, CHH, J = 16.3 Hz, J = 12.3 Hz); 3.03 (dd, 1 H, CHH,
J = 16.3 Hz, J = 3.5 Hz); 4.46—4.57 (m, 1 H, CH); 5.41 (br.s,
2
2 H, NH2); 6.22 (dddd, 1 H, CF2CF2H, JH,F = 53.6 Hz,
2JH,F = 52.4 Hz, 3JH,F = 7.5 Hz, 3JH,F = 3.8 Hz); 6.91 (dd, 1 H,
H(8), J = 8.3 Hz, J = 1.0 Hz); 7.03 (ddd, 1 H, H(6), J = 7.9 Hz,
J = 7.3 Hz, J = 1.2 Hz); 7.23 (ddd, 1 H, H(7), J = 8.3 Hz,
J = 7.3 Hz, J = 1.7 Hz); 7.91 (dd, 1 H, H(5), J = 7.9 Hz,
J = 1.7 Hz).
2ꢀTrifluoromethylchromanꢀ4ꢀone Nꢀ(1ꢀmethylethylidene)ꢀ
hydrazone (10a). A solution of hydrazone 9а (100 mg, 0.44 mmol)
in acetone (2 mL) was refluxed for 3 h and then poured into
water (15 mL). The crystals precipitated were filtered off and
washed with water. Azine 10a was obtained in a yield of 110 mg
(94%), colorless crystals, m.p. 82—83 °C. Found (%): C, 57.53;
H, 4.82; N, 10.30. C13H13F3N2O. Calculated (%): C, 57.78;
H, 4.85; N, 10.37. IR, ν/cm–1: 1633, 1613, 1590, 1458.
1Н NMR (CDCl3), δ: 2.02 (s, 3 H, Me); 2.12 (s, 3 H, Me); 2.60
(dd, 1 H, CHH, J = 16.6 Hz, J = 12.5 Hz); 3.60 (dd, 1 H, CHH,
J = 16.9 Hz, J = 3.3 Hz); 4.48 (dqd, 1 H, CH, J = 12.5 Hz,
J = 5.9 Hz, J = 3.3 Hz); 7.01 (dd, 1 H, H(8), J = 8.3 Hz, J = 1.0 Hz);
7.05 (ddd, 1 H, H(6), J = 7.9 Hz, J = 7.3 Hz, J = 1.2 Hz); 7.34
(ddd, 1 H, H(7), J = 8.4 Hz, J = 7.3 Hz, J = 1.7 Hz); 8.13 (dd,
1 H, H(5), J = 7.9 Hz, J = 1.7 Hz).
The bromination of chromanone 3а in acetic acid gave a
mixture of transꢀ12 and cisꢀ12 with 3,3ꢀdibromoꢀ2ꢀtrifluoroꢀ
methylchromanꢀ4ꢀone in a ratio of 77 : 16 : 7, respectively,
in 29% yield. This mixture was not separated. 1Н NMR of
3,3ꢀdibromoꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (CDCl3), δ: 4.94
(q, 1 H, H(2), J = 5.8 Hz); 7.15—7.25 (m, 2 H, H(6), H(8));
7.66 (m, 1 H, H(7)); 8.05 (dd, 1 H, H(5), J = 7.9 Hz, J = 1.7 Hz).
(Е)ꢀ3ꢀBenzylideneꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (13).
Benzaldehyde (200 mg, 1.81 mol) was added to a solution
of chromanone 3а (300 mg, 1.39 mmol) in isopropyl alcohol
(5 mL), and the obtained solution was cooled and saturated with
hydrogen chloride. The mixture was stored for 2 days at ~20 °C,
after which it was concentrated by evaporation to 2 mL and
cooled down. The crystals formed were filtered off and recrysꢀ
tallized from ethanol. Product 13 was obtained in a yield
of 80 mg (19%) as light beige crystals. m.p. 106—107 °C.
Found (%): C, 67.15; H, 3.68; F, 18.53. C17H11F3O2. Calculꢀ
ated (%): C, 67.11; H, 3.64; F, 18.73. IR, ν/cm–1: 1680,
2ꢀ(1,1,2,2ꢀTetrafluoroethyl)chromanꢀ4ꢀone Nꢀ(1ꢀmethylꢀ
ethylidene)hydrazone (10b) was obtained similarly to azine 10а
in 80% yield (110 mg from 120 mg of hydrazone 9b), colorless
crystals, m.p. 84—85 °C. Found (%): C, 55.37; H, 4.70; N, 9.21.
C14H14F4N2O. Calculated (%): C, 55.63; H, 4.67; N, 9.27.
1
IR, ν/cm–1: 1631, 1617, 1600, 1482, 1460. Н NMR (CDCl3),
δ: 2.01 (s, 3 H, Me); 2.12 (s, 3 H, Me); 2.64 (dd, 1 H, CHH,
J = 17.0 Hz, J = 12.7 Hz); 3.58 (dd, 1 H, CHH, J = 17.0 Hz,
J = 3.0 Hz); 4.48—4.59 (m, 1 H, CH); 6.19 (dddd, 1 H,
2
2
3
CF2CF2H, JH,F = 53.6 Hz, JH,F = 52.4 Hz, JH,F = 7.5 Hz,
3JH,F = 3.8 Hz); 6.94 (dd, 1 H, H(8), J = 8.3 Hz, J = 0.9 Hz);
7.05 (ddd, 1 H, H(6), J = 8.0 Hz, J = 7.3 Hz, J = 1.1 Hz); 7.33
(ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 8.14 (dd,
1 H, H(5), J = 8.0 Hz, J = 1.6 Hz).
2ꢀTrifluoromethylchromanꢀ4ꢀone Nꢀ(2ꢀtrifluoromethylꢀ
chromanꢀ4ꢀylidene)hydrazone (11). Triethyl borate (1 mL,
860 mg, 5.88 mmol) was added to a solution of hydrazone 3а
(650 mg, 2.83 mmol) in ethanol (10 mL). The mixture was
stirred for 30 min at ~20 °С, after which 11 М hydrochloric acid
(3 mL) was added dropwise with stirring and cooling. The further
stirring of the reaction mixture for 2 h resulted in the precipitation
of a plentiful yellowish precipitate. Then water (20 mL)
was added to the mixture, and the precipitate formed was
filtered off, multiply washed with water, and dried. Azine 11
was obtained in a yield of 400 mg (66%), light yellow thin
needles, m.p. 262—263 °С (subl.). Found (%): C, 56.05; H, 3.11;
N, 6.45. C20H14F6N2O2. Calculated (%): C, 56.08; H, 3.29;
N, 6.54. IR, ν/cm–1: 1606, 1463. 1Н NMR (DMSOꢀd6), δ:
(major isomer, 58%) 2.91 (dd, 1 H, CHH, J = 17.1 Hz, J = 11.7 Hz);
3.59 (dd, 1 H, CHH, J = 17.1 Hz, J = 3.7 Hz); 5.17—5.27 (m,
1 H, CH); 7.11 (dd, 1 H, H(8), J = 8.3 Hz, J = 1.1 Hz); 7.17
(ddd, 1 H, H(6), J = 7.9 Hz, J = 7.3 Hz, J = 1.1 Hz); 7.48 (ddd,
1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.6 Hz); 8.15 (dd, 1 H,
1
1611, 1583, 1463. Н NMR (CDCl3), δ: 5.90 (q, 1 H, H(2),
3JH,F = 6.9 Hz); 7.02 (d, 1 H, H(8), J = 8.3 Hz); 7.12 (t, 1 H,
H(6), J = 7.6 Hz); 7.43—7.51 (m, 5 H, Ph); 7.54 (ddd, 1 H,
H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 8.03 (dd, 1 H, H(5),
J = 7.9 Hz, J = 1.7 Hz); 8.15 (s, 1 H, =CH).
(Е)ꢀ3ꢀDimethylaminomethylideneꢀ2ꢀtrifluoromethylchromanꢀ
4ꢀone (14a). A mixture of chromanone 3а (4.0 g, 18.5 mmol)
and DMF dimethylacetal (7.7 g, 64.7 mmol) was refluxed for
1 h. Then an excess of DMF dimethylacetal was distilled off
in vacuo, and the residue was recrystallized from methanol.
Aminoenone 14a was obtained in a yield of 3.15 g (63%)
as yellow crystals, m.p. 145—146 °C. Found (%): C, 57.51;
H, 4.38; N, 5.02. C13H12F3NO2. Calculated (%): C, 57.57;
H, 4.46; N, 5.16. IR, ν/cm–1: 1655, 1608, 1586, 1560, 1478,
1462. 1Н NMR (CDCl3), δ: 3.21 (s, 6 H, 2 Me); 5.85 (br.q, 1 H,
CH, J = 6.7 Hz); 6.94 (dd, 1 H, H(8), J = 8.3 Hz, J = 0.7 Hz);

2ꢀ(Polyfluoroalkyl)chromanꢀ4ꢀols and ꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2473
7.04 (ddd, 1 H, H(6), J = 7.8 Hz, J = 7.3 Hz, J = 1.0 Hz); 7.40
(ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.85 (br.s,
1 H, =CH); 7.97 (dd, 1 H, H(5), J = 7.8 Hz, J = 1.7 Hz).
(Е)ꢀ3ꢀDimethylaminomethylideneꢀ2ꢀ(1,1,2,2ꢀtetrafluoroꢀ
ethyl)chromanꢀ4ꢀone (14b) was synthesized similarly to aminoꢀ
enone 14а in 59% yield (180 mg from 250 mg of chromanone
3b) as yellow crystals, m.p. 90—91 °C. Found (%): C, 57.51;
H, 4.38; N, 5.02. C14H13F4NO2. Calculated (%): C, 55.45;
H, 4.32; N, 4.62. IR, ν/cm–1: 1652, 1607, 1594, 1561, 1463.
1Н NMR (CDCl3), δ: 3.19 (s, 6 H, 2 Me); 5.9—6.0 (br.s, 1 H, CH);
6.02 (ddd, 1 H, CF2CF2H, JH,F = 53.8 Hz, JH,F = 52.5 Hz,
3JH,F = 10.7 Hz); 6.86 (dd, 1 H, H(8), J = 8.2 Hz, J = 0.8 Hz);
7.04 (td, 1 H, H(6), J = 7.7 Hz, J = 1.0 Hz); 7.39 (ddd, 1 H, H(7),
J = 8.2 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.91 (br.s, 1 H, =CH); 7.98
(dd, 1 H, H(5), J = 7.8 Hz, J = 1.7 Hz).
References
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7. T. Hiyama, Organofluorine Compounds. Chemistry and Appliꢀ
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(Z)ꢀ3ꢀAnilinomethylideneꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone
(15a). A solution of aminoenone 14а (250 mg, 0.93 mmol) and
aniline (130 mg, 1.40 mmol) in toluene (3 mL) was refluxed for
8 h. The obtained mixture was diluted with heptane (2 mL) and
cooled to 0 °С. The bright yellow crystals precipitated were
filtered off, washed with heptane, and dried. Aminoenone 15a
was obtained in a yield of 222 mg (75%), m.p. 114—115 °C.
Found (%): C, 63.85; H, 3.54; N, 4.42. C17H12F3NO2. Calꢀ
culated (%): C, 63.95; H, 3.79; N, 4.39. IR, ν/cm–1: 1654,
1606, 1597, 1585, 1568, 1506, 1470. 1Н NMR (CDCl3), δ: 5.21
8. V. Ya. Sosnovskikh, B. I. Usachev, D. V. Sevenard, G.ꢀV.
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2000, 238.
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3
(q, 1 H, CH, JH,F = 7.2 Hz); 7.01 (dd, 1 H, H(8), J = 8.3 Hz,
J = 0.8 Hz); 7.10 (ddd, 1 H, H(6), J = 7.8 Hz, J = 7.3 Hz,
J = 1.0 Hz); 7.12—7.18 (m, 3 H, arom.); 7.36—7.41 (m, 2 H,
arom.); 7.43 (d, 1 H, =CH, J = 13.0 Hz); 7.45 (ddd, 1 H,
H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.94 (dd, 1 H, H(5),
J = 7.8 Hz, J = 1.7 Hz); 12.19 (br.d, 1 H, NH, J = 13.0 Hz).
1Н NMR (DMSOꢀd6), δ: (Zꢀisomer, 79%) 5.86 (q, 1 H, CH,
3JH,F = 7.7 Hz); 7.08—7.45 (m, 7 H, Н(6), Н(8), Ph); 7.55
(ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.85 (dd, 1 H,
H(5), J = 7.8 Hz, J = 1.7 Hz); 8.16 (d, 1 H, =CH, J = 12.8 Hz);
12.87 (br.d, 1 H, NH, J = 12.8 Hz); (Eꢀisomer, 21%) 6.38 (q,
1 H, CH, 3JH,F = 7.3 Hz); 7.08—7.45 (m, 7 H, Н(6), Н(8), Ph);
7.54 (ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.86
(dd, 1 H, H(5), J = 7.8 Hz, J = 1.7 Hz); 8.30 (d, 1 H, =CH,
J = 14.2 Hz); 10.01 (br.d, 1 H, NH, J = 14.2 Hz).
(Z)ꢀ3ꢀ(pꢀAnisidino)methylideneꢀ2ꢀtrifluoromethylchromanꢀ
4ꢀone (15b) was obtained similarly to aminoenone 15а in 88%
yield (340 mg from 300 mg of aminoenone 14а) as yellow crystals,
m.p. 152—153 °C. Found (%): C, 61.59; H, 4.03; N, 4.04.
C18H14F3NO3. Calculated (%): C, 61.89; H, 4.04; N, 4.01.
IR, ν/cm–1: 1645, 1604, 1587, 1561, 1517, 1467. 1Н NMR
(DMSOꢀd6), δ: (Zꢀisomer, 80%) 3.76 (s, 3 H, MeO); 5.82 (q,
1 H, CH, 3JH,F = 7.7 Hz); 7.00 (d, 2 H, H(3´), H(5´), J = 9.1 Hz);
7.08 (dd, 1 H, Н(8), J = 8.3 Hz, J = 0.8 Hz); 7.14 (td, 1 H, Н(6),
J = 7.5 Hz, J = 1.0 Hz); 7.33 (d, 2 H, H(2´), H(6´), J = 9.1 Hz);
7.52 (ddd, 1 H, H(7), J = 8.3 Hz, J = 7.3 Hz, J = 1.7 Hz); 7.82
(dd, 1 H, H(5), J = 7.8 Hz, J = 1.7 Hz); 8.04 (br.d, 1 H, =CH,
J = 11.0 Hz); 11.92 (br.d, 1 H, NH, J = 11.0 Hz); (Eꢀisomer, 20%)
3.75 (s, 3 H, MeO); 6.30 (q, 1 H, CH, 3JH,F = 7.2 Hz); 6.98 (d,
2 H, H(3´), H(5´), J = 9.1 Hz); 7.07 (dd, 1 H, Н(8), J = 8.3 Hz,
J = 0.8 Hz); 7.11 (td, 1 H, Н(6), J = 7.5 Hz, J = 1.0 Hz); 7.24 (d,
2 H, H(2´), H(6´), J = 9.1 Hz); 7.51 (ddd, 1 H, H(7), J = 8.3 Hz,
J = 7.3 Hz, J = 1.7 Hz); 7.83 (dd, 1 H, H(5), J = 7.8 Hz, J = 1.7 Hz);
8.20 (br.s, 1 H, =CH); 9.90 (br.s, 1 H, NH).
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This work was financially supported by the Russian
Foundation for Basic Research (Project No. 06ꢀ03ꢀ32388).
Received December 12, 2008