Spiro[4H-chromene-4,5′-isoxazolines] and related compounds: Synthesis and reactivities

Article abstract of DOI:10.1007/s11172-006-0288-x

Reactions of chromones with methyl ketoximes in the presence of lithium diisopropylamide follow the nucleophilic 1,2-addition mechanism to give spiro[4H-chromene-4,5′-isoxazolines] in good yields. The isoxazoline ring in spiro[4H-chromene-4,5′-isoxazolines] undergoes opening under the action of conc. H₂SO₄, yielding α,β-unsaturated oximes. Their nitrosation and bromination lead to the corresponding spiroisoxazolines, while the Beckmann rearrangement, to α,β- unsaturated amides. The latter are also formed directly from spiro[4H-chromene-4,5′-isoxazolines] under the action of PCl₅. N-Substituted acetophenone hydrazones in the presence of lithium diisopropylamide react at the C(4) atom of 2-trifluoromethylchromone, while acetophenone anil under the same conditions, at the C(2) atom.

Full text of DOI:10.1007/s11172-006-0288-x

Russian Chemical Bulletin, International Edition, Vol. 55, No. 3, pp. 535—542, March, 2006
535
Spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines] and related compounds:
synthesis and reactivities
V. Ya. Sosnovskikh,aꢀ A. Yu. Sizov,a B. I. Usachev,a M. I. Kodess,b and V. A. Anufrieva
aA. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vyacheslav.Sosnovskikh@usu.ru
bI. Ya. Postovskii Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences,
20 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Reactions of chromones with methyl ketoximes in the presence of lithium diisopropylamide
follow the nucleophilic 1,2ꢀaddition mechanism to give spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines]
in good yields. The isoxazoline ring in spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines] undergoes openꢀ
ing under the action of conc. H2SO4, yielding α,βꢀunsaturated oximes. Their nitrosation and
bromination lead to the corresponding spiroisoxazolines, while the Beckmann rearrangement,
to α,βꢀunsaturated amides. The latter are also formed directly from spiro[4Hꢀchromeneꢀ4,5´ꢀ
isoxazolines] under the action of PCl5. NꢀSubstituted acetophenone hydrazones in the presꢀ
ence of lithium diisopropylamide react at the C(4) atom of 2ꢀtrifluoromethylchromone, while
acetophenone anil under the same conditions, at the C(2) atom.
Key words: chromones, dilithio oximes and dilithio hydrazones, spiro[4Hꢀchromeneꢀ4,5´ꢀ
isoxazolines] and spiro[4Hꢀchromoneꢀ4,5´ꢀpyrazolines], α,βꢀunsaturated oximes and amides,
Beckmann rearrangement, nitrosation, bromination.
Scheme 1
Chromone (4Hꢀchromenꢀ4ꢀone, 4Hꢀ1ꢀbenzopyranꢀ
4ꢀone) is a parent structure for an important class of
oxygenꢀcontaining heterocycles, in particular, flavone
(2ꢀphenylchromone) derivatives, which are widely enꢀ
countered in the plant world. These compounds exhibit a
variety of biological activity1 and find application as acꢀ
tive principles in a number of pharmaceutical prepaꢀ
rations including antitumor2 drugs. The chemistry of
chromones has been much investigated;1,3—5 however,
data on reactions of 2ꢀsubstituted chromones with
Cꢀnucleophiles are very scarce. Recently, we have demonꢀ
strated that dinucleophiles such as methyl ketone imines
(1,3ꢀC,Nꢀ and 1,3ꢀC,Cꢀdinucleophiles)6,7 and alkyl
mercaptoacetates (1,2ꢀS,Cꢀdinucleophiles)8 react with
2ꢀRFꢀchromones at the C(2) atom with cleavage of the
O(1)—C(2) bond followed by condensation at the carboꢀ
nyl group to give RFꢀcontaining aromatic and heterocyꢀ
clic compounds. Reactions of 2ꢀRFꢀchromones with
Cꢀnucleophiles such as trimethyl(trifluoromethyl)silane
(Ruppert´s reagent) and lithium enolates of aryl methyl
ketones also occur at the C(2) atom, but without openꢀ
ing of the pyrone ring, yielding 1,4ꢀaddition products:
2,2ꢀbis(trifluoromethyl)chromanꢀ4ꢀones9 and 2ꢀphenꢀ
acylꢀ2ꢀtrifluoromethylchromanꢀ4ꢀones,10 respectively
(Scheme 1).
We found that unlike reactions with Ruppert´s reagent
and lithium enolates of methyl ketones, condensation
of 2ꢀtrifluoromethylchromones with lithiated oximes
and hydrazones of methyl ketones follows the nucleoꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 516—522, March, 2006.
1066ꢀ5285/06/5503ꢀ0535 © 2006 Springer Science+Business Media, Inc.

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Sosnovskikh et al.
philic 1,2ꢀaddition mechanism, affording derivatives of
spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazoline] and spiro[4Hꢀchroꢀ
meneꢀ4,5´ꢀpyrazoline], which are novel spiroannulated
heterocyclic systems (see preliminary communication11).
cyclodehydration into spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazoꢀ
lines] 2.
Treatment of compounds 2a—c with conc. H2SO4 at
∼20 °C for 20 min followed by hydrolysis with water gave,
through opening of the isoxazoline ring, α,βꢀunsaturated
oximes 3a—c in 45—85% yields. This outcome was quite
unexpected and is specific to the spiro[chromeneꢀ4,5´ꢀ
isoxazoline] system. Earlier,22,23 the opening of the
2ꢀisoxazoline ring has been reported to occur only in the
presence of bases.
Most likely, the driving force of the opening of the
spiro node under the action of H2SO4 is the formation of
intermediate aromatic benzopyrilium cation A, whose
deprotonation gives α,βꢀenoximes 3. An analogous transꢀ
formation was observed in the treatment of oximes 1a,b
with H2SO4: their dehydration into compounds 3a,b also
proceeded through intermediate cation A undergoing subꢀ
sequent deprotonation.
Results and Discussion
1,4ꢀDianions generated from methyl ketoximes by
nꢀbutyllithium or lithium diisopropylamide are valuable
intermediates in organic synthesis. Condensation of
C,Oꢀlithiated oximes with various electrophilic substrates
such as esters,12—15 amides,16—18 ketones, and α,βꢀunsatꢀ
urated ketones19,20 ensures a regiocontrolled approach to
βꢀoxo and βꢀhydroxy oximes, which easily undergo acidꢀ
catalyzed cyclodehydration into isoxazoles and 2ꢀisoxazoꢀ
lines. However, reactions of dilithio oximes with chroꢀ
mones have not been studied hitherto.
We found that a reaction of acetophenone Eꢀoxime21
with 2.2 equiv. of lithium diisopropylamide in ether at
0 °C followed by addition of 2ꢀtrifluoromethylchromones
(–20 °C→∼20 °C, 2 h) and hydrolysis of the resulting mixꢀ
ture with water gives βꢀhydroxy oximes 1a,b in good yields.
In acidic media, oximes 1a,b easily undergo cyclization
(via dehydration) into spiroisoxazolines 2a,b, which can
also be obtained without the formation of oximes 1 if the
reaction mixture is treated with dilute HCl. In the case of
aliphatic oximes, unstable intermediate βꢀhydroxy oximes
1c,d were not isolated: spiroisoxazolines 2c,d were directly
obtained in 64 and 26% yields, respectively (Scheme 2).
This reaction is an earlier unknown transformation at the
C(4) atom of the chromone system, which should be
regarded as nucleophilic 1,2ꢀaddition of dilithio oxime
with the formation of a new C—C bond followed by
The Eꢀconfiguration of the exoꢀcyclic C=C bond in
oximes 3 was proved by the 2D NOESY technique. The
2D NOESY spectrum of compound 3a shows crossꢀpeaks
between the signals for the proton of the exoꢀC=C bond
(δ 6.79) and for the aromatic H(5) proton (δ 7.86). In the
oxime fragments of compounds 1 and 3, the antiꢀarrangeꢀ
ment of the hydroxy and phenyl groups was expected
Scheme 2
a
H
Ph
b
Me
Ph
c
H
Me
d
H
But
R1
R2

Spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines]
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
537
since the Eꢀconfiguration of the starting oxime is retained
during the reaction.17,24 This was confirmed by the strucꢀ
tures of the products of the Beckmann rearrangement,
which is known25 to involve intramolecular migration of
the substituent in the antiꢀposition relative to the leaving
OH group.
additional evidence for the Eꢀconfiguration of the C=N
bond of oximes 3, because it has been shown earlier26
that 4ꢀhydroxyiminoisoxazolines are formed only from
α,βꢀenoximes in which the OH group is syn to the double
bond. For the antiꢀarrangement of these functions, the
major products are 1ꢀhydroxypyrazole 2ꢀoxides resulting
from an initial attack of the nitrosonium cation at the
oxime N atom.26
It is known that halogenation of α,βꢀunsaturated
oximes with Nꢀhalosuccinimides affords 4ꢀhaloisoxazoꢀ
lines.27 In our case, oximes 3a,b easily reacted with broꢀ
mine in CHCl3 at ∼20 °C to give 4ꢀbromoisoxazolines
6a,b as mixtures of two diastereomers in 89—92% yields
(the ratio of the diastereomers was 92 : 8 for 6a and 96 : 4
for 6b). Under analogous conditions, spiroisoxazoline 2a
resisted bromination, being recovered unchanged. Note
that when the molar ratio of oxime 3b to bromine was
1 : 1.5 (the same as was used in the halogenation of
compound 3a), we obtained a mixture of 4ꢀbromoꢀ and
4,4ꢀdibromoisoxazolines in the ratio 62 : 38, respectively.
Individual compound 6b was obtained from an equimolar
mixture of the reagents, while the use of a twoꢀ to threeꢀ
fold excess of bromine always gave a mixture of monoꢀ
and dibromo derivatives.
Indeed, oximes 1a,b and 3a,b in the presence of PCl5
in ether at ∼20 °C were rearranged into amides 4a,b in
high yields; therefore, in compounds 1 and 3, the subꢀ
stituent R2 is anti to the N—O bond. Interestingly, the
Beckmann rearrangement easily occurs not only with
oximes 1 and 3 but also with spiroisoxazolines 2a—d,
which behave like a latent oxime form under these condiꢀ
tions. This reaction is the first example of involvement of
the isoxazoline ring in the Beckmann rearrangement withꢀ
out isolation of the corresponding α,βꢀunsaturated oxime.
Note that spiroisoxazoline 2d did not undergo opening
into enoxime 3 on treatment with H2SO4, while in
the presence of PCl5, it immediately transformed into
amide 4d; hence, the rearrangement 2→4 occurs at the
step of the formation of benzopyrilium cation A.
The stereochemistry of amides 4 was determined
and their H(3) and =CH protons were assigned from
the 2D NOESY and 2D HSQC data for amide 4c. Its
2D NOESY spectrum shows crossꢀpeaks between the sigꢀ
nals for the =CH, H(5), and NH protons and no crossꢀ
peaks with the H(3) proton, which suggests the Eꢀconꢀ
figuration of the exoꢀmethylene double bond and the preꢀ
ferred sꢀcisꢀconformation. Indeed, the signal for the H(3)
proton in the 1H NMR spectra of amides 4 appears in the
unusually low field (δ 8.42—8.49) in both CDCl3 and
DMSOꢀd6. Such a strong deshielding of the H(3) proton,
whose signal in chromones usually appears at δ 6—7, is
due to the close vicinity of the carbonyl O atom and the
H(3) atom, which is possible only in the sꢀcisꢀconformer.
In the 13C NMR spectrum of compound 4c, the signal for
the C(3) atom was easily identified from splitting at the
The relatively easy formation of compounds 5a,b and
6a,b upon an electrophilic attack on the αꢀC atom of the
exocyclic double bond in oximes 3 can be associated with
stable chromylium intermediate A undergoing rapid cyꢀ
clization into a spiro system. Nevertheless, a reaction of
oxime 3a with such an electrophilic reagent as acetyl chloꢀ
ride occurred at the hydroxy group (∼20 °C, 1 h), affordꢀ
ing compound 7 in 67% yield (Scheme 3).
Scheme 3
3
F atoms with JC,F = 4.2 Hz. In turn, the 2D HSQC
spectrum shows a crossꢀpeak between the signal for this
C atom and a singlet at δ 8.48, which allows unambiguous
assignment of this singlet to the H(3) proton.
Apart from the Beckmann rearrangement, we studied
other reactions of α,βꢀunsaturated oximes 3a,b. We found
that nitrosation of these compounds with NaNO2 in diꢀ
lute HCl gives hydroxyiminospiroisoxazolines 5a,b in
78 and 59% yields, respectively; in this case, no deoximaꢀ
tion products were detected (Scheme 3). Apparently, the
transformation of enoxime 3 into spiroisoxazoline 5 inꢀ
volves an electrophilic attack of the nitrosonium cation at
the αꢀposition of compound 3; the resulting cationic speꢀ
cies, due to the presence of the hydroxy group, undergoes
cyclization into 4ꢀnitrosoisoxazoline existing in the oxime
form 5. Despite possible geometrical isomerism at the
oxime group, compounds 5a,b were isolated as only one
stereoisomer. The formation of these products provides
R1 = H (a), Me (b)

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Sosnovskikh et al.
To determine the limits of application of the aforesaid
ethoxycarbonyl group; this can be attributed to hindered
rotation of the CO2Et group about the C—N bond.
reaction, we studied reactions of 2ꢀmethylchromone, flaꢀ
vone, and chromone with acetophenone oxime in the
presence of lithium diisopropylamide. We found that deꢀ
spite the known tendency of the 2ꢀmethyl group to be
deprotonated by bases,28 2ꢀmethylchromone under these
conditions gives spiroisoxazoline 2e in a virtually quantiꢀ
tative yield. An analogous reaction of flavone gave comꢀ
pound 2f in 65% yield (Scheme 4). However, in the case
of unsubstituted chromone, the reaction mixture almost
immediately turned dark red and underwent resinification,
probably because of the absence of a substituent in posiꢀ
tion 2 and the accessibility of the C(2) and H(2) atoms to
an attack by a base.29 It should also be noted that unlike
spiroisoxazolines 2a—d containing the CF3 group at
the C(2) atom, compounds 2e,f did not react with
conc. H2SO4, undergoing resinification under the action
of PCl5; this indicates a specific role of the CF3 group in
the aforesaid transformations.
Scheme 5
Scheme 4
Thus, in contrast to lithium enolates of ketones and aza
enolates of anils, lithiated oximes and hydrazones of meꢀ
thyl ketones react with chromones at the carbonyl C atom
(1,2ꢀaddition) to give, on acidification, spiro[4Hꢀchroꢀ
meneꢀ4,5´ꢀisoxazolines] and spiro[4Hꢀchromeneꢀ4,5´ꢀ
pyrazolines], which are of synthetic interest for further
modification at position 4 of the chromone system.
Experimental
R = Me (e), Ph (f)
IR spectra were recorded on IKSꢀ29 and Perkin—Elmer
Spectrum BXꢀII instruments (Nujol or KBr pellets). 1H and
13C NMR spectra were recorded on a Bruker DRXꢀ400 specꢀ
trometer (400.1 and 100.6 MHz, respectively) in CDCl3 with
Me4Si as the internal standard.
Literature data on reactions of chromones with
lithiated hydrazones and anils of methyl ketones are lackꢀ
ing. It is only known that the 1,4ꢀdianion of acetopheꢀ
none Nꢀethoxycarbonylhydrazone reacts with carbonyl
compounds such as esters, acyl chlorides, amides, and
αꢀhalo ketones to give pyrazole and pyrazoline derivaꢀ
tives.30 We found that a reaction of acetophenone diꢀ
methylhydrazone (in place of oximes) with 2ꢀtrifluoroꢀ
methylchromone gives βꢀhydroxy hydrazone 8 in 22%
yield as the result of nucleophilic addition of lithium aza
enolate to the oxo group of the chromone. An analogous
reaction with acetophenone Nꢀethoxycarbonylhydrazone
afforded spiropyrazoline 9 in 26% yield, which is also a
1,2ꢀadduct. However, acetophenone anil behaved differꢀ
ently under the same conditions, giving, via 1,4ꢀaddition,
2ꢀphenacylꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (10) in 69%
yield; earlier,10 we have obtained this compound in 32%
yield by the reaction of 2ꢀtrifluoromethylchromone with
lithium enolate of acetophenone (Scheme 5). It should be
Synthesis of βꢀhydroxy oximes 1a,b. Diisopropylamine
(1.87 g, 18.5 mmol) was added to a solution of nꢀbutyllithium
prepared from metallic Li (37.0 mmol) and nꢀbutyl bromide
(18.5 mmol) in anhydrous diethyl ether (10 mL). The mixture
was cooled with ice water and stirred for 30 min. Then a solution
of methyl ketoxime (8.4 mmol) in diethyl ether (5 mL) was
added to the resulting transparent solution of lithium diisoꢀ
propylamide. The mixture was stirred for 40 min and cooled
to –20 °C and a solution of an appropriate chromone (7.0 mmol)
in anhydrous THF (6 mL) was added. The reaction mixture was
stirred at ∼20 °C for 2 h and hydrolyzed with water (50 mL). The
product was extracted with ether (20 mL). The organic layer was
separated and concentrated and the resulting oil was triturated
with pentane to initiate crystallization. The solid product was
filtered off, dried, and recrystallized from an appropriate solvent.
2ꢀ(4ꢀHydroxyꢀ2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀyl)ꢀ1ꢀpheꢀ
nylethanꢀ1ꢀone oxime (1a). The yield was 72%, colorless needleꢀ
like crystals, m.p. 134—135 °C (CCl4). Found (%): C, 61.70;
H, 4.00; N, 3.98. C18H14F3NO3. Calculated (%): C, 61.89;
1
noted that the H NMR spectrum of spiropyrazoline 9
shows strongly broadened signals for the protons of the

Spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines]
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
539
H, 4.04; N, 4.01. IR, ν/cm–1: 3520 (OH), 3230 (NOH), 1695
(C=C), 1620, 1585 (arom.). 1H NMR (CDCl3), δ: 3.32 (d, 1 H,
CHH, J = 13.6 Hz); 3.72 (d, 1 H, CHH, J = 13.6 Hz); 4.0 (br.s,
1 H, OH); 5.67 (s, 1 H, H(3)); 7.01 (d, 1 H, H(8), Jo = 8.3 Hz);
7.14 (t, 1 H, H(6), Jo = 7.6 Hz); 7.22—7.40 (m, 6 H, H(7), Ph);
7.67 (d, 1 H, H(5), Jo = 7.8 Hz); 9.0 (br.s, 1 H, NOH).
7.14 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm = 1.2 Hz); 7.25 (ddd, 1 H,
H(6), Jo = 7.9 and 7.3 Hz, Jm = 1.2 Hz); 7.37 (ddd, 1 H, H(7),
Jo = 8.3 and 7.3 Hz, Jm = 1.6 Hz); 7.47 (dd, 1 H, H(5), Jo
7.9 Hz, Jm = 1.6 Hz).
=
3´ꢀtertꢀButylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ
4,5´,4´,5´ꢀdihydroisoxazole] (2d) was obtained under the conꢀ
ditions of the synthesis of oximes 1a,b by hydrolysis of the reacꢀ
tion mixture with dilute HCl (1 : 3). The yield was 26%, colorꢀ
less crystals, m.p. 84—85 °C (hexane). Found (%): C, 61.76;
H, 5.18; N, 4.33. C16H16F3NO2. Calculated (%): C, 61.73;
H, 5.18; N, 4.50. IR (KBr), ν/cm–1: 2975, 1703 (C=C), 1615,
1584, 1488 (arom.). 1H NMR (CDCl3), δ: 1.28 (s, 9 H, But);
3.17 (d, 1 H, CHH, J = 17.7 Hz); 3.38 (d, 1 H, CHH, J =
17.7 Hz); 5.84 (s, 1 H, H(3)); 7.13 (dd, 1 H, H(8), Jo = 8.3 Hz,
2ꢀ(4ꢀHydroxyꢀ6ꢀmethylꢀ2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀ
yl)ꢀ1ꢀphenylethanꢀ1ꢀone oxime (1b). The yield was 62%, colorꢀ
less needleꢀlike crystals, m.p. 156—157 °C (toluene—hexane
(2 : 1)). Found (%): C, 62.49; H, 4.34; N, 4.09. C19H16F3NO3.
Calculated (%): C, 62.81; H, 4.44; N, 3.85. IR (KBr), ν/cm–1
:
3535 (OH), 3245 (NOH), 1695 (C=C), 1495 (arom.). 1H NMR
(CDCl3), δ: 2.28 (s, 3 H, Me); 3.33 (d, 1 H, CHH, J = 13.5 Hz);
3.70 (d, 1 H, CHH, J = 13.5 Hz); 3.85 (s, 1 H, OH); 5.65 (s,
1 H, H(3)); 6.90 (d, 1 H, H(8), Jo = 8.4 Hz); 7.03 (dd, 1 H,
H(7), Jo = 8.4 Hz, Jm = 2.1 Hz); 7.26—7.35 (m, 3 H, H(3´),
H(4´), H(5´)); 7.40 (d, 1 H, H(5), Jm = 1.8 Hz); 7.41—7.43 (m,
2 H, H(2´), H(6´)); 8.3 (br.s, 1 H, NOH).
Jm = 1.1 Hz); 7.24 (ddd, 1 H, H(6), Jo = 7.9 and 7.3 Hz, Jm
=
1.1 Hz); 7.36 (ddd, 1 H, H(7), Jo = 8.3 and 7.3 Hz, Jm = 1.6 Hz);
7.45 (dd, 1 H, H(5), Jo = 7.9 Hz, Jm = 1.6 Hz).
2ꢀMethylꢀ3´ꢀphenylspiro[4Hꢀchromeneꢀ4,5´,4´,5´ꢀdihydroꢀ
isoxazole] (2e) was obtained from 2ꢀmethylchromone as deꢀ
scribed for compounds 2c,d. The yield was 97%, colorless
needles, m.p. 131—132 °C (ethanol). Found (%): C, 78.03;
H, 5.31; N, 5.22. C18H15NO2. Calculated (%): C, 77.96; H, 5.45;
N, 5.05. IR (KBr), ν/cm–1: 1695 (C=C), 1616, 1595, 1581,
1568, 1486 (arom.). 1H NMR (CDCl3), δ: 2.06 (d, 1 H, Me, J =
0.8 Hz); 3.42 (d, 1 H, CHH, J = 17.4 Hz); 3.70 (d, 1 H, CHH,
J = 17.4 Hz); 5.12 (q, 1 H, H(3), J = 0.8 Hz); 7.05 (dd, 1 H,
3´ꢀPhenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ4,5´,4´,5´ꢀ
dihydroisoxazole] (2a). A solution of conc. HCl (0.5 mL) in
ethanol (2 mL) was added to a solution of compound 1a (490 mg,
1.4 mmol) in ethanol (3 mL). This immediately resulted in the
formation of a copious white precipitate. The mixture was stirred
for 5 min and then diluted with water (5 mL). The precipitate
was filtered off, washed with water, dried, and recrystallized
from ethanol. The yield was 83%, colorless needleꢀlike crystals,
m.p. 124—125 °C.
H(8), Jo = 8.4 Hz, Jm = 1.1 Hz); 7.13 (ddd, 1 H, H(6), Jo
=
Spiroisoxazoline 2a was also obtained in 53% yield under
the conditions of the synthesis of oximes 1a,b by hydrolysis of
the reaction mixture with a solution of oxalic acid. Found (%):
C, 65.18; H, 3.43; N, 4.20. C18H12F3NO2. Calculated (%):
C, 65.26; H, 3.65; N, 4.23. IR, ν/cm–1: 1695 (C=C), 1615,
7.9 and 7.2 Hz, Jm = 1.1 Hz); 7.30 (ddd, 1 H, H(7), Jo = 8.4 and
7.2 Hz, Jm = 1.6 Hz); 7.41—7.45 (m, 3 H, H(3´), H(4´), H(5´));
7.46 (dd, 1 H, H(5), Jo = 7.9 Hz, Jm = 1.6 Hz); 7.69—7.73 (m,
2 H, H(2´), H(6´)).
2,3´ꢀDiphenylspiro[4Hꢀchromeneꢀ4,5´,4´,5´ꢀdihydroꢀ
isoxazole] (2f) was obtained from flavone as described for comꢀ
pounds 2c,d. The yield was 65%, colorless needles, m.p.
124—125 °C (ethanol). Found (%): C, 81.28; H, 5.01; N, 4.15.
C23H17F3NO2. Calculated (%): C, 81.40; H, 5.05; N, 4.13.
IR (KBr), ν/cm–1: 1665 (C=C), 1615, 1595, 1585, 1565, 1495
(arom.). 1H NMR (CDCl3), δ: 3.57 (d, 1 H, CHH, J = 17.4 Hz);
3.80 (d, 1 H, CHH, J = 17.4 Hz); 5.84 (s, 1 H, H(3)); 7.19 (ddd,
1 H, H(6), Jo = 7.9 and 7.2 Hz, Jm = 1.1 Hz); 7.23 (dd, 1 H,
1
1595, 1585 (arom.). H NMR (CDCl3), δ: 3.57 (d, 1 H, CHH,
J = 17.5 Hz); 3.78 (d, 1 H, CHH, J = 17.5 Hz); 5.95 (s, 1 H,
H(3)); 7.18 (dd, 1 H, H(8), Jo = 8.4 Hz, Jm = 1.1 Hz); 7.24 (ddd,
1 H, H(6), Jo = 7.9 and 7.3 Hz, Jm = 1.1 Hz); 7.39 (ddd, 1 H,
H(7), Jo = 8.4 and 7.3 Hz, Jm = 1.6 Hz); 7.42—7.49 (m, 3 H,
H(3´), H(4´), H(5´)); 7.52 (dd, 1 H, H(5), Jo = 7.9 Hz, Jm
1.6 Hz); 7.68—7.73 (m, 2 H, H(2´), H(6´)).
=
6ꢀMethylꢀ3´ꢀphenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ
4,5´,4´,5´ꢀdihydroisoxazole] (2b) was obtained analogously from
compound 1b. The yield was 89%, colorless needleꢀlike crystals,
m.p. 135—136 °C (ethanol). Found (%): C, 66.04; H, 4.10;
N, 3.87. C19H14F3NO2. Calculated (%): C, 66.09; H, 4.09;
H(8), Jo = 8.4 Hz, Jm = 1.1 Hz); 7.37 (ddd, 1 H, H(7), Jo
=
8.4 and 7.2 Hz, Jm = 1.6 Hz); 7.40—7.46 (m, 6 H, arom.);
7.54 (dd, 1 H, H(5), Jo = 7.9 Hz, Jm = 1.6 Hz); 7.72—7.80
(m, 4 H, arom.).
Synthesis of α,βꢀunsaturated oximes 3a—c. Concentrated
H2SO4 (3 mL) was added to spiroisoxazoline 2 (0.7 mmol). The
reaction mixture was stirred at ∼20 °C for 20 min and poured
into ice water (10 mL). The precipitate that formed was filtered
off, washed with water, dried, and recrystallized from toluene.
Under analogous conditions, compounds 3a,b were also obꢀ
tained from oximes 1a,b.
N, 4.06. IR (KBr), ν/cm–1
:
1700 (C=C), 1595, 1570,
1500 (arom.). 1H NMR (CDCl3), δ: 2.32 (s, 3 H, Me); 3.55 (d,
1 H, CHH, J = 17.5 Hz); 3.78 (d, 1 H, CHH, J = 17.5 Hz); 5.91
(s, 1 H, H(3)); 7.07 (d, 1 H, H(8), Jo = 8.5 Hz); 7.18 (br.dd,
1 H, H(7), Jo = 8.5 Hz, Jm = 2.0 Hz); 7.28 (br.d, 1 H, H(5), Jm
=
2.0 Hz); 7.44—7.48 (m, 3 H, H(3´), H(4´), H(5´)); 7.70—7.73
(m, 2 H, H(2´), H(6´)).
3´ꢀMethylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ4,5´,4´,5´ꢀ
dihydroisoxazole] (2c) was obtained under the conditions of the
synthesis of oximes 1a,b by hydrolysis of the reaction mixture
with dilute HCl (1 : 3). The yield was 64%, colorless needleꢀlike
crystals, m.p. 96—97 °C (hexane—CHCl3). Found (%): C, 57.88;
H, 3.97; N, 5.35. C13H10F3NO2. Calculated (%): C, 58.00;
H, 3.74; N, 5.20. IR (KBr), ν/cm–1: 1698 (C=C), 1636, 1617,
1588, 1493 (arom.). 1H NMR (CDCl3), δ: 2.09 (t, 3 H, Me, 4J =
1ꢀPhenylꢀ2ꢀ(2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)ethanꢀ
1ꢀone oxime (3a). The yield was 85% (89% from 1a), light yelꢀ
low needles, m.p. 174—175 °C. Found (%): C, 65.38; H, 3.63;
N, 4.22. C18H12F3NO2. Calculated (%): C, 65.26; H, 3.65;
N, 4.23. IR, ν/cm–1: 3200 (OH), 1675 (C=C), 1620, 1595, 1575
(arom.). 1H NMR (CDCl3), δ: 6.03 (s, 1 H, H(3)); 6.79 (s, 1 H,
=CH); 7.18 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm = 1.2 Hz); 7.27
(ddd, 1 H, H(6), Jo = 8.1 and 7.3 Hz, Jm = 1.2 Hz); 7.38—7.44
(m, 4 H, H(7), H(3´), H(4´), H(5´)); 7.56—7.59 (m, 2 H, H(2´),
H(6´)); 7.86 (dd, 1 H, H(5), Jo = 8.1 Hz, Jm = 1.6 Hz); 8.0—9.0
2
4
1.0 Hz); 3.13 (dq, 1 H, CHH, J = 17.9 Hz, J = 1.0 Hz); 3.35
(dq, 1 H, CHH, 2J = 17.9 Hz, 4J = 1.0 Hz); 5.86 (s, 1 H, H(3));

540
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
Sosnovskikh et al.
1
(br.s, 1 H, OH). H NMR (DMSOꢀd6), δ: 6.00 (s, 1 H, H(3));
pound 3b. The yield was 87%, light yellow needles, m.p.
201—202 °C (toluene). Found (%): C, 66.01; H, 4.08; N, 3.82.
6.92 (s, 1 H, =CH); 7.30 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm
=
1.2 Hz); 7.36 (ddd, 1 H, H(6), Jo = 8.1 and 7.3 Hz, Jm = 1.2 Hz);
7.41—7.44 (m, 3 H, H(3´), H(4´), H(5´)); 7.50 (ddd, 1 H, H(7),
Jo = 8.3 and 7.3 Hz, Jm = 1.5 Hz); 7.55—7.58 (m, 2 H, H(2´),
H(6´)); 8.07 (dd, 1 H, H(5), Jo = 8.1 Hz, Jm = 1.5 Hz); 11.70
(s, 1 H, OH).
C19H14F3NO2. Calculated (%): C, 66.09; H, 4.09; N, 4.06.
IR (KBr), ν/cm–1: 3435, 3280 (NH), 1670, 1635 (C=O, NH),
1590, 1525, 1490 (arom.). 1H NMR (CDCl3), δ: 2.41 (s, 3 H,
Me); 6.12 (s, 1 H, =CH); 7.12 (t, 1 H, H(4´), Jo = 7.4 Hz); 7.17
(d, 1 H, H(8), Jo = 8.5 Hz); 7.28—7.31 (m, 2 H, H(7), NH);
7.33—7.37 (m, 2 H, H(3´), H(5´)); 7.52 (br.s, 1 H, H(5));
7.54—7.60 (m, 2 H, H(2´), H(6´)); 8.48 (s, 1 H, H(3)). 1H NMR
(DMSOꢀd6), δ: 2.41 (s, 3 H, Me); 6.60 (s, 1 H, =CH); 7.07 (tt,
1 H, H(4´), Jo = 7.4 Hz, Jm = 1.1 Hz); 7.32 (d, 1 H, H(8), Jo =
8.5 Hz); 7.31—7.35 (m, 2 H, H(3´), H(5´)); 7.43 (br.dd, 1 H,
H(7), Jo = 8.5 Hz, Jm ~ 2.0 Hz); 7.62 (br.s, 1 H, H(5)); 7.66—7.69
(m, 2 H, H(2´), H(6´)); 8.47 (s, 1 H, H(3)); 10.16 (s, 1 H, NH).
NꢀMethylꢀ(2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)acetꢀ
amide (4c) was obtained analogously from compound 2c. The
yield was 89%, light yellow crystals, m.p. 191—192 °C (toluꢀ
ene). Found (%): C, 57.76; H, 3.93; N, 5.19. C13H10F3NO2.
2ꢀ(6ꢀMethylꢀ2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)ꢀ1ꢀ
phenylethanꢀ1ꢀone oxime (3b). The yield was 72% (71% from 1b),
light yellow needles, m.p. 170—171 °C. Found (%): C, 65.87;
H, 4.14; N, 3.88. C19H14F3NO2. Calculated (%): C, 66.09;
H, 4.09; N, 4.06. IR (KBr), ν/cm–1: 3235 (OH), 1680 (C=C),
1605, 1490 (arom.). 1H NMR (CDCl3), δ: 2.41 (s, 3 H, Me);
6.01 (s, 1 H, H(3)); 6.77 (s, 1 H, =CH); 7.07 (d, 1 H, H(8), Jo =
8.4 Hz); 7.21 (br.dd, 1 H, H(7), Jo = 8.4 Hz, Jm = 1.7 Hz);
7.38—7.43 (m, 3 H, H(3´), H(4´), H(5´)); 7.56—7.59 (m, 2 H,
H(2´), H(6´)); 7.65 (br.s, 1 H, H(5)); 7.9—8.8 (br.s, 1 H, OH).
1ꢀ(2ꢀTrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)acetone oxime
(3c). The yield was 45%, light yellow crystals, m.p. 160—162 °C.
Found (%): C, 56.81; H, 3.86; N, 5.10. C13H10F3NO2•1/3H2O.
Calculated (%): C, 58.00; H, 3.74; N, 5.20. IR (KBr), ν/cm–1
:
3280 (NH), 1675, 1630 (C=O, NH), 1595, 1560 (arom.).
1H NMR (DMSOꢀd6), δ: 2.70 (d, 3 H, Me, J = 4.8 Hz); 6.40 (s,
1 H, =CH); 7.35—7.42 (m, 2 H, H(8), H(6)); 7.56 (ddd, 1 H,
H(7), Jo = 8.4 and 7.2 Hz, Jm = 1.4 Hz); 7.75 (dd, 1 H, H(5),
Jo = 8.1 Hz, Jm = 1.4 Hz); 8.08 (br.q, 1 H, NH, J = 4.8 Hz); 8.48
(s, 1 H, H(3)). 13C NMR (DMSOꢀd6), δ: 25.43 (Me), 105.45 (q,
C(3), 3JC,F = 4.2 Hz), 109.67 (C(4´)), 118.05 (C(8)), 119.21 (q,
Calculated (%): C, 56.73; H, 3.91; N, 5.09. IR (KBr), ν/cm–1
:
3181, 3118 (OH), 1668, 1634, 1609, 1589, 1575, 1483 (arom.).
1H NMR (CDCl3), δ: 2.16 (s, 3 H, Me); 6.61 (s, 1 H, H(3));
6.63 (s, 1 H, =CH); 7.17 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm
=
1.2 Hz); 7.23 (ddd, 1 H, H(6), Jo = 8.2 and 7.1 Hz, Jm = 1.2 Hz);
7.38 (ddd, 1 H, H(7), Jo = 8.3 and 7.1 Hz, Jm = 1.5 Hz); 7.74
(dd, 1 H, H(5), Jo = 8.2 Hz, Jm = 1.5 Hz); 7.0—8.0 (br.s, 1 H,
OH). 1H NMR (DMSOꢀd6), δ: 2.07 (s, 3 H, Me); 6.64 (s, 1 H,
H(3)); 6.72 (s, 1 H, =CH); 7.29 (dd, 1 H, H(8), Jo = 8.3 Hz,
Jm = 1.0 Hz); 7.32 (ddd, 1 H, H(6), Jo = 8.1 and 7.1 Hz,
1
CF3, JC,F = 271.5 Hz), 119.25 (C(4a)), 122.84 (C(5)), 126.10
2
(C(6)), 131.22 (C(4)), 131.72 (C(7)), 139.93 (q, C(2), JC,F
=
36.8 Hz), 150.30 (C(8a)), 166.13 (C=O).
NꢀtertꢀButylꢀ(2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)acetꢀ
amide (4d) was obtained analogously from compound 2d. The
yield was 63%, light yellow crystals, m.p. 217—218 °C (toluene).
Found (%): C, 61.69; H, 5.17; N, 4.21. C16H16F3NO2. Calcuꢀ
lated (%): C, 61.73; H, 5.18; N, 4.50. IR (KBr), ν/cm–1: 3285
(NH), 1670, 1635 (C=O, NH), 1600, 1555 (arom.). 1H NMR
(CDCl3), δ: 1.43 (s, 9 H, But); 5.43 (br.s, 1 H, NH); 5.93 (s,
1 H, =CH); 7.21—7.25 (m, 2 H, H(8), H(6)); 7.43 (ddd, 1 H,
H(7), Jo = 8.4 and 7.2 Hz, Jm = 1.5 Hz); 7.65 (dd, 1 H, H(5),
Jo = 8.3 Hz, Jm = 1.5 Hz); 8.42 (s, 1 H, H(3)).
3´ꢀPhenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ4,5´,4´,5´ꢀ
dihydroisoxazol]ꢀ4´(5´H )ꢀone oxime (5a). Sodium nitrite (50
mg, 0.7 mmol) was added to a solution of oxime 3a (200 mg,
0.6 mmol) in an ethanol—water—THF mixture (1 : 2 : 2; 5 mL).
Then the stirred mixture was acidified dropwise with aqueous
HCl (1 : 3) to pH 1—2. The solvent was removed, the solid
residue was treated with water, and the precipitate was filtered
off, dried, and recrystallized from hexane—chloroform (3 : 1).
The yield was 78%, colorless needles, m.p. 157—158 °C.
Found (%): C, 59.99; H, 3.26; N, 7.82. C18H11F3N2O3. Calcuꢀ
lated (%): C, 60.01; H, 3.08; N, 7.77. IR (KBr), ν/cm–1: 3250
(OH), 1695 (C=C), 1615, 1585, 1490 (arom.). 1H NMR
(CDCl3), δ: 5.80 (s, 1 H, H(3)); 7.20 (td, 1 H, H(6), Jo = 7.8 Hz,
Jm = 1.1 Hz); 7.23 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm = 1.1 Hz);
7.24 (dd, 1 H, H(5), Jo = 8.0 Hz, Jm = 1.7 Hz); 7.42 (m, 1 H,
H(7)); 7.45—7.52 (m, 3 H, H(3´), H(4´), H(5´)); 7.60 (s,
1 H, OH); 8.07—8.10 (m, H(2´), H(6´)). MS (EI, 70 eV),
m/z (Irel (%)): 360 [M]+ (40), 343 (100), 299 (43), 240 (27),
224 (99), 129 (22), 77 (23). Found: m/z 360.0711 [M]+.
Jm = 1.0 Hz); 7.47 (ddd, 1 H, H(7), Jo = 8.3 and 7.1 Hz, Jm
=
1.4 Hz); 7.87 (dd, 1 H, H(5), Jo = 8.1 Hz, Jm = 1.4 Hz); 10.95
(s, 1 H, OH).
NꢀPhenylꢀ(2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylidene)acetꢀ
amide (4a). Phosphorus pentachloride (330 mg, 1.6 mmol) was
added to a solution of oxime 3a (265 mg, 0.8 mmol) in anꢀ
hydrous diethyl ether (10 mL). The reaction mixture was stirred
at ∼20 °C for 30 min and poured into water (30 mL). The prodꢀ
uct was extracted with ether (20 mL). The organic layer was
separated and concentrated and the solid residue was recrystalꢀ
lized from toluene. Under analogous conditions, amide 4a was
also obtained from oxime 1a and spiroisoxazoline 2a. The yield
was 84 (from 3a), 79 (from 1a), and 80% (from 2a), light yellow
needles, m.p. 191—192 °C. Found (%): C, 65.37; H, 3.66;
N, 4.11. C18H12F3NO2. Calculated (%): C, 65.26; H, 3.65;
N, 4.23. IR (KBr), ν/cm—1: 3420, 3300 (NH), 1670, 1640 (C=O,
NH), 1595, 1540, 1530, 1500 (arom.). 1H NMR (CDCl3), δ:
6.14 (s, 1 H, =CH); 7.12 (t, 1 H, H(4´), J = 7.3 Hz); 7.25—7.29
(m, 2 H, H(6), H(8)); 7.32—7.36 (m, 3 H, H(3´), H(5´), NH);
7.48 (ddd, 1 H, H(7), Jo = 8.3 and 7.3 Hz, Jm = 1.0 Hz);
7.54—7.60 (m, 2 H, H(2´), H(6´)); 7.72 (br.d, 1 H, H(5), Jo
7.0 Hz); 8.49 (s, 1 H, H(3)). H NMR (DMSOꢀd6), δ: 6.63 (s,
1 H, =CH); 7.07 (tt, 1 H, H(4´), Jo= 7.4 Hz, Jm = 1.1 Hz);
≈
1
7.31—7.36 (m, 2 H, H(3´), H(5´)); 7.42 (dd, 1 H, H(8), Jo
8.3 Hz, Jm = 1.1 Hz); 7.46 (ddd, 1 H, H(6), Jo = 8.2 and 7.3,
Jm = 1.1 Hz); 7.61 (ddd, 1 H, H(7), Jo = 8.5 and 7.3 Hz, Jm
=
=
1.5 Hz); 7.66—7.70 (m, 2 H, H(2´), H(6´)); 7.82 (dd, 1 H,
H(5), Jo = 8.2 Hz, Jm = 1.5 Hz); 8.48 (s, 1 H, H(3)); 10.19
(s, 1 H, NH).
C18H11F3N2O3. Calculated: M = 360.0722.
NꢀPhenylꢀ(6ꢀmethylꢀ2ꢀtrifluoromethylꢀ4Hꢀchromenꢀ4ꢀylꢀ
idene)acetamide (4b) was obtained analogously from comꢀ
6ꢀMethylꢀ3´ꢀphenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ
4,5´,4´,5´ꢀdihydroisoxazol]ꢀ4´(5´H )ꢀone oxime (5b) was obꢀ

Spiro[4Hꢀchromeneꢀ4,5´ꢀisoxazolines]
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 3, March, 2006
541
tained analogously from compound 3b. The yield was 59%, colꢀ
orless needles, m.p. 168—169 °C. Found (%): C, 60.97; H, 3.51;
N, 7.58. C19H13F3N2O3. Calculated (%): C, 60.97; H, 3.50;
hydrazone (0.91 g, 5.6 mmol) in anhydrous THF (5 mL) was
added with stirring. The resulting light yellow solution was stirred
at ∼20 °C for 30 min and cooled to –30 °C. A solution of
2ꢀtrifluoromethylchromone (1.0 g, 4.7 mmol) in anhydrous THF
(5 mL) was added. The reaction mixture was stirred at ∼20 °C
for 12 h and hydrolyzed with water (50 mL). The product was
extracted with ether (20 mL). The organic layer was separated,
dried, and concentrated. The resulting light yellow oil was trituꢀ
rated with pentane to initiate crystallization. The solid prodꢀ
uct was filtered off and recrystallized from hexane to give comꢀ
pound 8 (0.40 g, 22%) as light yellow crystals, m.p. 129—130 °C.
Found (%): C, 63.95; H, 5.13; N, 7.44. C20H19F3N2O3. Calcuꢀ
lated (%): C, 63.82; H, 5.09; N, 7.44. IR, ν/cm–1: 3300 (OH),
N, 7.48. IR (KBr), ν/cm–1
: 3250 (OH), 1695 (C=C),
1500 (arom.). H NMR (CDCl3), δ: 2.30 (s, 3 H, Me); 5.76 (s,
1 H, H(3)); 6.99 (br.d, 1 H, H(5), Jm = 2.0 Hz); 7.11 (d, 1 H,
1
H(8), Jo = 8.5 Hz); 7.21 (ddq, 1 H, H(7), Jo = 8.5 Hz, Jm
=
2.1 Hz, JH,CH = 0.5 Hz); 7.44—7.52 (m, 3 H, H(3´), H(4´),
3
H(5´)); 7.64 (s, 1 H, OH); 8.08—8.11 (m, 2 H, H(2´), H(6´)).
4´ꢀBromoꢀ3´ꢀphenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ
4,5´,4´,5´ꢀdihydroisoxazole] (6a). A solution of bromine
(110 mg, 0.69 mmol) in chloroform (2 mL) was added dropwise
to a solution of enoxime 3a (150 mg, 0.45 mmol) in dry chloroꢀ
form (2 mL). The mixture was stirred at ∼20 °C for 10 min,
whereupon the solvent was removed and the solid residue was
kept in boiling ethanol (3 mL) for 5 min. On cooling, the preꢀ
cipitate that formed was filtered off, washed with ethanol, and
dried. The yield was 89%, colorless needles, m.p. 136—137 °C.
Found (%): C, 52.53; H, 2.71; N, 3.51. C18H11BrF3NO2. Calꢀ
1
1695 (C=C), 1605 (arom.). H NMR (CDCl3), δ: 2.72 (s, 6 H,
2 Me); 3.19 (d, 1 H, CHH, J = 13.9 Hz); 3.50 (d, 1 H, CHH, J =
13.9 Hz); 5.69 (s, 1 H, H(3)); 7.10 (dd, 1 H, H(8), Jo = 8.2 Hz,
Jm = 1.1 Hz); 7.16 (ddd, 1 H, H(6), Jo = 7.8 and 7.5 Hz, Jm
=
1.1 Hz); 7.25—7.31 (m, 3 H, H(7), H(3´), H(5´)); 7.36 (m, 1 H,
H(4´)); 7.47—7.50 (m, 2 H, H(2´), H(6´)); 7.66 (dd, 1 H, H(5),
Jo = 7.8 Hz, Jm = 1.6 Hz); 9.3 (br.s, 1 H, OH).
culated (%): C, 52.71; H, 2.70; N, 3.41. IR (KBr), ν/cm—1
:
1697 (C=C), 1615, 1585, 1564, 1485 (arom.). 1H NMR (CDCl3),
Ethyl
3´ꢀphenylꢀ2ꢀtrifluoromethylspiro[4Hꢀchromeneꢀ
δ: 5.53 (s, 1 H, CH); 6.19 (s, 1 H, H(3)); 7.17 (ddd, 1 H, H(6),
4,5´,4´,5´ꢀdihydroꢀ1Hꢀpyrazole]ꢀ1´ꢀcarboxylate (9) was obꢀ
tained from 2ꢀtrifluoromethylchromone and acetophenone
Nꢀethoxycarbonylhydrazone as described above for compound
8 by hydrolysis of the reaction mixture with dilute HCl (1 : 3).
The yield of compound 9 was 26%, light yellow crystals, m.p.
201—202 °C (toluene—hexane). Found (%): C, 62.55; H, 4.14;
N, 6.93. C21H17F3N2O3. Calculated (%): C, 62.69; H, 4.26;
N, 6.96. IR (KBr), ν/cm–1: 1721 (C=O), 1602, 1585 (arom.).
1H NMR (CDCl3), δ: 0.7—1.4 (br.s, 3 H, Me); 3.61 (d, 1 H,
CHH, J = 17.8 Hz); 3.81 (d, 1 H, CHH, J = 17.8 Hz); 3.9—4.4
(br.s, 2 H, OCH2); 5.75 (s, 1 H, H(3)); 7.10—7.16 (m, 2 H,
H(6), H(8)); 7.30—7.34 (m, 2 H, H(5), H(7)); 7.41—7.45 (m,
3 H, H(3´), H(4´), H(5´)); 7.77—7.79 (m, 2 H, H(2´), H(6´)).
2ꢀPhenacylꢀ2ꢀtrifluoromethylchromanꢀ4ꢀone (10) was obꢀ
tained from 2ꢀtrifluoromethylchromone and acetophenone anil
as described for compound 8 by hydrolysis of the reaction mixꢀ
ture with dilute HCl (1 : 3). The yield of compound 10 was 69%,
m.p. 81—82 °C (hexane—CCl4). Compound 10 has been deꢀ
scribed earlier.10
Jo = 8.1 and 7.2 Hz, Jm = 1.1 Hz); 7.25 (dd, 1 H, H(8), Jo
=
8.6 Hz, Jm = 1.1 Hz); 7.33 (dd, 1 H, H(5), Jo = 8.1 Hz, Jm
=
1.6 Hz); 7.42 (ddd, 1 H, H(7), Jo = 8.6 and 7.2 Hz, Jm = 1.6 Hz);
7.47—7.52 (m, 3 H, H(3´), H(4´), H(5´)); 7.83—7.87 (m,
H(2´), H(6´)).
4´ꢀBromoꢀ6ꢀmethylꢀ3´ꢀphenylꢀ2ꢀtrifluoromethylspiro[4Hꢀ
chromeneꢀ4,5´,4´,5´ꢀdihydroisoxazole] (6b) was obtained analoꢀ
gously from compound 3b for the equimolar ratio of 3b
to Br2. The yield was 92%, colorless needles, m.p. 156—157 °C.
Found (%): C, 53.83; H, 3.17; N, 3.40. C19H13BrF3NO2. Calꢀ
culated (%): C, 53.80; H, 3.09; N, 3.30. IR (KBr), ν/cm–1: 1697
(C=C), 1592, 1564, 1498 (arom.). 1H NMR (CDCl3), δ: 2.26 (s,
3 H, Me); 5.54 (s, 1 H, CH); 6.14 (s, 1 H, H(3)); 7.08 (br.s, 1 H,
H(5)); 7.13 (d, 1 H, H(8), Jo = 8.5 Hz); 7.22 (br.dd, 1 H, H(7),
Jo = 8.5 Hz, Jm = 1.7 Hz); 7.47—7.52 (m, 3 H, H(3´), H(4´),
H(5´)); 7.83—7.87 (m, 2 H, H(2´), H(6´)).
4ꢀ(2ꢀAcetoxyiminoꢀ2ꢀphenylethylidene)ꢀ2ꢀtrifluoromethylꢀ
4Hꢀchromene (7). Acetyl chloride (55 mg, 0.7 mmol) was added
to a solution of oxime 3a (200 mg, 0.6 mmol) in diethyl ether
(10 mL). The mixture was stirred at ∼20 °C for 1 h and concenꢀ
trated. The solid residue was recrystallized from hexane. The
yield of compound 7 was 0.15 g (67%), yellowish crystals,
m.p. 141—142 °C. Found (%): C, 64.43; H, 3.70; N, 3.52.
This work was financially supported by the Civilian
Research and Development Foundation of the United
States (CRDF) and the Ministry of Education and Sciꢀ
ence of the Russian Federation (Grant Nos EKꢀ005ꢀX1
and Y1ꢀ005ꢀ04).
C
20H14F3NO3. Calculated (%): C, 64.34; H, 3.78; N, 3.75.
IR (KBr), ν/cm–1: 1772 (CO), 1671 (C=C), 1600, 1541 (arom.).
1H NMR (CDCl3), δ: 2.27 (s, 3 H, Me); 5.98 (s, 1 H, H(3));
6.75 (s, 1 H, =CH); 7.23 (dd, 1 H, H(8), Jo = 8.3 Hz, Jm
=
References
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Received June 24, 2005;
in revised form February 1, 2006