Transformations of gem-dibromoarylcyclopropanes under nitrosation conditions on treatment with NOCl·(SO3)n

Article abstract of DOI:10.1007/s11172-016-1439-3

The reaction of 2-aryl-1,1-dibromocyclopropanes with adduct NOCl·(SO₃)_n leading to 3-aryl-5-bromoisoxazoles as a result of nitrosation—heterocyclization of the cyclopropane ring was studied. The reaction is accompanied with electroph

Full text of DOI:10.1007/s11172-016-1439-3

Russian Chemical Bulletin, International Edition, Vol. 65, No. 5, pp. 1225—1231, May, 2016
1225
Transformations of gemꢀdibromoarylcyclopropanes
under nitrosation conditions on treatment with NOCl•(SO3)n*
O. B. Bondarenko,a A. Yu. Gavrilova,a S. N. Nikolaeva,a and N. V. Zyka,b
aDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 939 4652. Eꢀmail: bondarenko@org.chem.msu.ru
bInstitute of Physiologically Active Compounds, Russian Academy of Sciences,
1 Severnyi proezd, Chernogolovka, 142432 Moscow Region, Russian Federation
The reaction of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes with adduct NOCl•(SO3)n leading to
3ꢀarylꢀ5ꢀbromoisoxazoles as a result of nitrosation—heterocyclization of the cyclopropane ring
was studied. The reaction is accompanied with electrophilic aromatic bromination. The mechꢀ
anism of the transformation was discussed, the optimal reaction conditions to enhance the
reaction selectivity were developed.
Key words: 2ꢀarylꢀ1,1ꢀdibromocyclopropanes, nitrosation, adduct NOCl•(SO3)n, 3ꢀarylꢀ
5ꢀbromoisoxazoles, electrophilic aromatic bromination.
Haloisoxazoles are very promising for further chemiꢀ
cal transformations. They found wide application in the
transition metal catalyzed crossꢀcouplings (the Heck reacꢀ
tion, the Stille coupling, the Suzuki, Sonogashira, and
Nigishi crossꢀcouplings)1,2 opening a versatile excess to
highlyꢀsubstituted isoxazoleꢀcontaining frameworks and
are used for the design of the combinatorial libraries of
new heterocyclic compounds.3—5 It is of note that bioꢀ
screening and structural design of the isoxazole derivatives
are of great interest due to a known wide range of physioꢀ
logical activity exhibiting by isoxazoles; they are also the
constituent parts of many pharmaceuticals used for the
treatment of various disorders.6—10. Haloisoxazoles possess
different biological activity (for instance, anthelmintic11
and herbicide12) and a series of other useful properties.13
It is known that direct halogenation of isoxazole ring
proceeds exclusively as 4ꢀhalogenation.14—17 The attempts
to lithiate isoxazoles in the positions 3 or 5 followed by
halogenation were unsatisfactory since the reactions are
accompanied by the N—O bond cleavage and the ring
pounds in moderate yields. Thus, the development of versaꢀ
tile preparative procedure to access 5ꢀbromoisoxazoles is
still ongoing challenge.
5ꢀHaloisoxazoles can be synthesized by nitrosation of
gemꢀdihalocyclopropanes.21 It is notable that the starting
compounds are readily available. Synthesis of gemꢀdihaloꢀ
cyclopropanes via the Doering reaction22 under phaseꢀ
transfer catalysis conditions23 leads to nearly unlimited
number of substrates varying in structure.
Studying nitrosation reactions, we introduced the adꢀ
duct of nitrosyl chloride with sulfur trioxide as a nitrosatꢀ
ing agent.24 According to Paul et al.,25 the NOCl•(SO3)n
adduct comprises either one or two molecules of sulfur
trioxide. We successfully used this adduct in the synthesis
of isoxazolines from arylcyclopropanes bearing in the aroꢀ
matic ring both electronꢀdonating and electronꢀwithdrawꢀ
ing substituents.26 This adduct was found very promising
for nitrosation of gemꢀdichlorocyclopropanes of different
structures including polycyclic species.27,28 In the present
work, we describe the behavior of gemꢀdibromoarylcycloꢀ
propanes under nitrosation with the adduct of nitrosyl
chloride with sulfur trioxide.
Preliminary experiments have shown that nitrosation
of the small ring of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes 1a—e
and subsequent heterocyclization led to the corresponding
3ꢀarylꢀ5ꢀbromoisoxazoles 2a—e. However, despite the
complete conversion of the starting compounds the yields
of the target isoxazoles were relatively low (Schemes 1—3).
Isolation of all products of the reaction of cyclopropane
1a with the NOCl•(SO3)n adduct by preparative column
chromatography gave the following compounds: 5ꢀbroꢀ
opening.18—19
.
To date, several approaches to 5ꢀbromoisoxazoles have
been described. For instance, 5ꢀbromoisoxazoles have been
synthesized by the reaction of phosphorus oxybromide with
3ꢀarylisoxazolones, which in turn have been prepared by
the reaction of βꢀketo esters with hydroxylamine.12,20 The
other approach is 1,3ꢀdipolar cycloaddition of nitrile
oxides to alkynes.5 Both methods produce the target comꢀ
* Dedicated to Academician of the Russian Academy of Sciences
O. G. Sinyashin on the occasion of his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1225—1231, May, 2016.
1066ꢀ5285/16/6505ꢀ1225 © 2016 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
Bondarenko et al.
Scheme 3
moꢀ3ꢀphenylisoxazole (2a) contaminated with isoxazole
2b and cyclopropanes 3 identified by H NMR spectrosꢀ
1
copy and LC/MS (see Scheme 1).
Scheme 1
Reagents and conditions: NOCl•(SO3)n (1.5 equiv.), MeNO2,
20 °C.
In the case of paraꢀsubstituted aryldibromocycloꢀ
propanes 1b—d, isoxazoles 4a—c bearing two bromine atꢀ
oms in the isoxazole cycle were isolated along with isoxꢀ
azoles 2b—d (see Scheme 2).
Reagents and conditions: NOCl•(SO3)n (1.8 equiv.), MeNO2,
20 °C, 20 h.
Scheme 2
the presence of the C(4)—H bond.29 The C(5) atom signal
is shifted to the strong field by ∼14.0 ppm than the same
signal of 5ꢀchloroisoxazoles,28 which can be explained by
a heavy atom effect.30 Note that in the case of arylated
gemꢀdibromocyclopropanes nitrosation—heterocyclizaꢀ
tion reaction sequence involving the small ring is regioseꢀ
lective and gives exclusively 3ꢀarylꢀ5ꢀbromoisoxazoles
2a—d; other regioisomers were not detected.
1H NMR spectra of isoxazoles 4a—d exhibit only aroꢀ
matic proton signals. In 13C NMR spectra, a weak signal
of the C(4) atom, which is in a quaternary state, is shifted
upfield by ∼9.0 ppm as compared with the similar signal of
isoxazoles 2a—e (heavy atom effect) and appeared at
δC ∼95.0. The compositions of isoxazoles 4a—d were conꢀ
firmed by elemental analysis and mass spectrometry data.
The cleavage pattern of the molecular ions of compounds
4a—c showing the fragment ion with m/z 114 correspondꢀ
ing to the [C6H4C2N]+ azirinium ion indicates the presꢀ
ence of the aromatic substituent at the C(3) heterocyclic
carbon atom. Thus, compounds 4a—d are the products of
bromination of isoxazoles 2b—e at the 4ꢀposition.
The structure of cyclopropane 5 was examined by Xꢀray
diffraction analysis (Fig. 1). The unit cell contains two
symmetrically independent molecules with nearly the same
conformations. The spectral and microanalysis data are
in complete agreement with the Xꢀray data. From Fig. 1
it follows that the benzene ring plane significantly deviꢀ
ates from the plane passing though the bisector of the
C(8)—C(7)—C(9) angle thereby lowering the conjugation
between the small ring and the aromatic system. This deꢀ
viation can be explained by the effect of the orthoꢀsubstitꢀ
R = Br (1b, 2b, 4a), Cl (1c, 2c, 4b), NO2 (1d, 2d, 4c)
Reagents and conditions: NOCl•(SO3)n (1.5 equiv.), MeNO2,
20 °C, 20 h.
Nitrosation of 2ꢀ(3ꢀbromophenyl)ꢀ1,1ꢀdibromocycloꢀ
propane (1e) afforded equal amounts of isoxazole 2e and
gemꢀdibromoarylcyclopropane 5 and small amounts of
isoxazole 4d (see Scheme 3).
Structures and compositions of the isolated compounds
were established by spectral methods (Table 1) and eleꢀ
mental analysis.
In 1H NMR spectra, heterocyclic protons of isoxazoles
2a—e resonate as singlets at about δH 6.60, which is charꢀ
acteristic of the H(4) proton of the isoxazole cycle.29 In
13C NMR spectra of isoxazoles 2a—e, three characteristic
signals of the isoxazole ring carbon atoms were observed,
namely, two lowꢀfield weak signals at δC 163.0 (C=N)
and 142.0 (BrC—O) corresponding to the quaternary carꢀ
bon atoms and an intense signal at δC 104.0 confirming

Nitrosation of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1227
Table 1. 1H and 13C NMR spectra (CDCl3) of isoxazoles 2a—e and 4a—d
Comꢀ
pound
1H NMR, δH (J/Hz)
13C NMR, δ
C
C(4)H
Benzene ring
Isoxazole cycle
Benzene ring
Other
C atoms
C(3)
C(4)
C(5)
С—Het C—R
2а
2b
2c
2d
2e
6.62 7.50 (m, 3 Н), 7.78 (m, 2 Н)
164.2 104.4 141.7
163.3 104.3 142.2
163.2 104.3 142.1
163.0 104.7 143.9
163.0 104.4 142.2
128.0
126.9
126.5
129.1
129.9
130.5
125.0
136.7
149.2
123.1
126.7, 129.0
129.0, 132.3
128.0, 129.4
124.4, 127.7
125.3, 129.7,
130.6, 133.5
6.59 7.62 (d, 2 Н, 3J = 8.9); 7.65 (d, 2 Н, 3J = 8.9)
6.59 7.46 (d, 2 Н, 3J = 8.7); 7.72 (d, 2 Н, 3J = 8.7)
6.71 7.98 (d, 2 Н, 3J = 8.9); 8.36 (d, 2 Н, 3J = 8.9)
6.61 7.36 (t, 1 Н, 3J = 8.0); 7.62 (ddd, 1 Н,
3J = 8.0, 4J = 1.0, 4J = 1.9); 7.71 (ddd, 1 Н,
3J = 8.0, 4J = 1.0, 4J = 1.5); 7.94 (br.s, 1 H)
4a
4b
4c
4d
—
—
—
—
7.67 (d, 2 Н, 3J = 8.4); 7.75 (d, 2 Н, 3J = 8.4)
7.51 (d, 2 Н, 3J = 8.8); 7.82 (d, 2 Н, 3J = 8.8)
8.09 (d, 2 Н, 3J = 8.4); 8.40 (d, 2 Н, 3J = 8.4)
7.41 (t, 1 Н, 3J = 8.0); 7.68 (ddd, 1 Н,
3J = 8.0, 4J = 1.0, 4J = 2.0); 7.81 (ddd, 1 Н,
3J = 8.0, 4J = 1.0, 4J = 1.5); 8.02 (br.s, 1 Н)
161.4
161.3
160.5
161.0
95.8
95.8
95.9
95.8
144.0
143.9
144.8
144.0
125.5
125.5
129.8
128.9
125.9
137.1
149.2
122.9
129.6, 132.2
129.2, 129.4
124.1, 129.1
126.7, 130.4,
131.0, 133.8
uent. Consequently, cyclopropane 5 does not undergo
small ring nitrosation. Similar deactivation effect of the
orthoꢀsubstituent has been described for the series of nitroꢀ
substituted gemꢀdichloroarylcyclopropanes.28
Formation of isoxazoles 4a—c and cyclopropanes 3
and 5 can be regarded as a result of electrophilic aromatic
bromination. It is known14—17 that the isoxazole cycle
readily undergoes halogenation at the 4ꢀposition. For comꢀ
pound 1e, the concerted effect of the substituents at the
benzene ring facilitates electrophilic substitution reaction.
Since neither solvent nor nitrosating agent can serve as
a source of electrophilic bromine, we suggest that hydrogen
bromide formed in the reaction medium upon the isoxꢀ
azole synthesis undergoes oxidation and then reacts with
the starting cyclopropane or isoxazole. The role of oxidizꢀ
ing agent can play the nitrosonium cation, which is known
as a relatively strong oxidant.31 The generated brominatꢀ
ing species are further involved into electrophilic aromatic
substitution to produce the bromination products (Scheme 4).
Thus, we were able to demonstrate that the bulky
bromine atoms bonded to the small cycle impeding nitroꢀ
sation and releasing hydrogen bromide readily oxidizing
upon the reaction favor electrophilic aromatic bromination.
With the aim to optimize the conditions for the high
yields of isoxazoles 2a—e, we performed 1H NMR studies
of the reaction mixture compositions at different reaction
times using cyclopropane 1e as a model compound. It was
found that with the 1.5ꢀfold excess of the adduct the low
conversion of cyclopropane 1e was achieved; under these
conditions formation of isoxazole 2e was detected only 3 h
after the reaction onset. Note that 5 h after the reaction
onset, the reaction mixture contained equal amounts of
both isoxazole 2e and brominated cyclopropane 5 (Table 2,
entries 8—11). This fact indicates that hydrogen bromide
released upon the reaction readily oxidizes and is immeꢀ
diately involved in further transformations.
a
Br(3)
C(2)
C(3)
C(9)
Br(1)
C(1)
C(7)
C(6)
C(4)
C(8)
C(5)
Br(2)
Br(4)
b
Br(1)
Br(2)
C(9)
C(8)
C(7)
C(1)
Br(4)
C(6)
C(2)
C(5)
C(4)
C(3)
Br(3)
Fig. 1. General view of one of the crystallographically indepenꢀ
dent molecules of compound 5 in two different projections (a, b)
according to Xꢀray data. Nonꢀhydrogen atom are shown as 50%
thermal ellipsoids. Conformation of the second independent
molecule is virtually the same.
It is obvious that the rate of cyclopropane nitrosation
can be increased by increasing the concentration of the
reacting species. The compositions of the reaction mixtures

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Bondarenko et al.
a
Table 2. Nitrosation of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes with adduct NOCl•(SO3)n
Entry
Comꢀ
pound 1
[NO+]
/equiv.
[1]
/mol L–1
t/h
Conversion
Reaction products
1 (%)
(Yield (%))
1b,c
2b,c
3c
1а
1b
1b
1c
1c
1c
1c
1e
1e
1e
1e
1
2.5
4
4
4
4
6
1.5
1.5
1.5
1.5
0.30
0.20
0.06
0.06
0.06
0.06
0.05
0.10
0.10
0.10
0.10
1
4
0.25
0.25
0.5
1
0.25
0.25
1
189
180
175
175
185
100
175
110
110
115
140
2а (30) + 2b (8) + 3 (8)
2b (25) + 4a (25)
2b (50)
4c
2c (46)
5c
2c (45) + 4b (10)
2c (40) + 4b (30)
2c (56)
6c
7c
8
9
10
11
—
—
3
5
2e (5)
2e (20) + 5 (20)
a Reaction conditions: MeNO2, 20 °C.
b Reaction is accompanied by noticeable resinification.
c According 1H NMR spectroscopy, the reaction mixture contains also 1,3ꢀdisubstituted 1ꢀarylpropanes.
Scheme 4
(cf. Table 2, entries 8—11) and 1 h after the reaction onset
the content of isoxazole 2e riches 30%. Note that no forꢀ
mation of both cyclopropane 5 and isoxazole 4d was deꢀ
tected at the earlier stages of the reaction. An increase in
the reaction time results in formation and accumulation
of the products of bromination of the starting cycloproꢀ
pane 1e and/or formed isoxazole 2e. Similar results were
obtained for compound 1c (see Table 2, entries 4—6).
An increase in cyclopropane concentration is negaꢀ
tively affects the yield of isoxazoles. In the case of cycloꢀ
propanes 1a—c bearing substituents stabilizing the benzꢀ
ylic cation, we observed strong resinification of the reacꢀ
tion mixture and loss of chemoselectivity. Thus, at relaꢀ
tively high conversions of cyclopropanes 1a,b reaching
80% and more the yields of isoxazoles 2a,b do not exceed
25% due to formation of the large amounts of acyclic
products of 1,3ꢀnitrosohalogenation and threeꢀmembered
cycle halogenation28 (see Table 2, entries 1 and 2).
The yields of isoxazoles (without lowering the nitrosaꢀ
tion rate) can be increased by decreasing the cyclopropane
concentration and simultaneously increasing the nitrosatꢀ
Table 3. Effect of the reaction time on the compositions
of the reaction mixtures obtained by nitrosation of cycloꢀ
propane 1e*
Entry
t/h
Reaction mixture composition (%)
1e
2e
4d
5
1
2
3
4
0.25
75
70
6
25
30
40
36
—
—
30
35
—
—
24
29
1
3
5
obtained by nitrosation of cyclopropane 1e with an excess
of the nitrosating agent at different reaction times are sumꢀ
marized in Table 3. The data in Table 3 show that 4ꢀfold
molar excess of adduct NOCl•(SO3)n leads to a signꢀ
ificant increase in the conversion of cyclopropane 1e
—
* Reaction conditions: the starting concentration [1e] =
0.06 mol L–1, MeNO2, 20 °C, 1e : NOCl•(SO3)n = 1 : 4.

Nitrosation of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1229
Table 4. Effect of the reaction time and the starting concenꢀ
tration of the substrate on the compositions of the reaction
mixtures obtained by nitrosation of cyclopropane 1d*
ical shifts are given in the δ scale relative to hexamethyldisilꢀ
oxane (an internal standard). The accuracy of the chemical shift
measurements were 0.01 ppm, the accuracy of the spinꢀspin
coupling measurements were 0.1 Hz. IR spectra were recorded
using a URꢀ20 spectrophotometer in Nujol or neat. Mass spectroꢀ
metry was performed with a GC/MS Finnigan MAT SSQ 7000
system (energy of ionizing electrons of 70 eV; quartz capillary
column OVꢀ1 (25 m); temperature programming: 70 °C for 2 min,
heating at a rate of 20 °C min–1, maintaining at 280 °C for 10 min).
Melting points were measured with a MelꢀTempII apparatus
and given uncorrected. The reaction course and the purity of
compounds were monitored by TLC on the Silufol precoated
plates. All solvents were purified and dried following the stanꢀ
dard procedures.33 2ꢀArylꢀ1,1ꢀdibromocyclopropanes 1a—d
were synthesized as earlier described.34,35 1,1ꢀDibromoꢀ2ꢀ(4ꢀ
nitrophenyl)cyclopropane 1e was synthesized by direct nitration
of cyclopropane 1a.
Entry
[1d]/
/mol L–1
t/h
Reaction mixture composition (%)
1d
2d
4с
1
2
3
0.140
0.014
0.014
2.5
20
70
10
85
30
25
15
60
65
—
10
* Reaction conditions: NOCl•(SO3)n (4 equiv.), MeNO2, 20 °C.
ing agent concentration. The strong dilution leads also
to a decrease in both the oxidation rate of hydrogen
bromide due to its low concentration and the electrophilic
bromination rate also due to low concentration of the
reacting species. These facts are confirmed by the data
obtained upon nitrosation of cyclopropane 1d (Table 4).
At the relatively high starting concentration of cycloproꢀ
pane [1d] = 0.14 mol L–1 and at the presence of 4ꢀfold
excess of complex NOCl•(SO3)n, the conversion of this
substrate deactivated by the nitro group reached 90% within
2.5 h; however, the main component of the reaction mixꢀ
ture was 4,5ꢀdibromoisoxazole (4c) (see Table 4, entry 1).
The 10ꢀfold dilution of the reaction mixture retaining the
same reagent ratio (entry 2) led to a significant decrease in
the conversion of cyclopropane 1d; nevertheless, formaꢀ
tion of 4c was not observed. The relatively high yield of
isoxazole 2d free from dibromo derivative 4c or containing
minimum amount of 4c can be achieved carefully choosꢀ
ing the reaction time (entry 3).
Xꢀray diffraction study of cyclopropane 5 was performed
with a Bruker SMART APEX II CCD automatized diffractoꢀ
meter (graphite monochromator, λ(MoKα) = 0.71073 Å, ω scan
mode). Accounting empirical absorption and correction of systeꢀ
matic errors were performed by SADABS program.36 The strucꢀ
ture was solved by direct method and refined by fullꢀmatrix least
squares method against F2 with anisotropic thermal parameꢀ
hkl
ters for all nonꢀhydrogen atoms. Hydrogen atoms were calculatꢀ
ed geometrically and refined by the riding model with Uiso(Hi) =
= 1.2Ueq(Ci). Main crystallographic and refinement parameters
are given in Table 5. The structure was solved and refined with
SHELX program package, version SHELXLꢀ2014/7.37 Crystalloꢀ
graphic data for structure 5 were deposited with the Cambridge
Crystallographic Data Center38 (CCDC 1437333).
Table 5. Crystallographic characteristics, Xꢀray data colꢀ
lection, and refinement statistics for compound 5
The best results were obtained performing the reaction
for 30 min in the presence of 10ꢀfold excess of complex
NOCl•(SO3)n and at the cyclopropane concentration of
0.014—0.02 mol L–1. Under these conditions, the yields
of isoxazoles were 57—70%.32
In summary, we studied transformations of 2ꢀarylꢀ1,1ꢀ
dibromocyclopropanes on treatment with an adduct of
nitrosyl chloride with sulfur trioxide leading to 3ꢀarylꢀ5ꢀ
bromoisoxazoles via nitrosation—heterocyclization reacꢀ
tion sequence. It was found that hydrogen bromide reꢀ
leased upon the reaction readily oxidizes and reacts furꢀ
ther with species present in the reaction mixture following
the electrophilic aromatic substitution mechanism. We
optimized the reaction conditions towards chemoselecꢀ
tive formation of 3ꢀarylꢀ5ꢀbromoisoxazoles in good yields
and also gave reasonable explanation of this choice.
Parameter
Value
Molecular formula
Molecular weight
T/K
Crystal system
Space group
Z/Z´
a/Å
b/Å
C9H6Br4
433.78
120(2)
Rhombic
Pca21
8/2
11.9711(5)
8.7239(4)
21.1888(10)
2212.85(17)
2.604
145
1600
50
27202
6451
5507
235
0.0315
0.0496
1.034
c/Å
V/Å
3
dcalc/g cm–3
μ/cm–1
F(000)
2θmax/deg
Number of collected reflections
Number of independent reflections
Number of reflections with I > 2σ(I)
Number of refined parameters
R1
Experimental
wR2
GOF
The starting compounds and solvents were purchased from
Reakhim, Aldrich, and Acros Organic. 1H and 13C NMR spectra
were run with a Bruker Avanceꢀ400 instrument in CDCl3 at
working frequencies of 400 (1H) and 100 (13C) MHz. The chemꢀ
Residual electron density,
e Å–3 (ρmax/ρmin)
0.605/–0.739

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Bondarenko et al.
1
Nitrosation of 2ꢀarylꢀ1,1ꢀdibromocyclopropanes 1 with an
adduct NOCl•(SO3)n (general procedure). To adduct NOCl•
•(SO3)n (0.70—0.80 g, 3.0—3.5 mmol) in nitromethane (4 mL),
gemꢀdibromoarylcyclopropane 1 (2.0 mmol) in nitromethane
(1 mL) was added and the resulting solution was stirred for 20 h
at room temperature (∼20 °C). After the reaction completion
(TLC monitoring), the reaction mixture was neutralized with
a NaHCO3 solution and washed with water. The combined aqueous
layers were extracted with chloroform (3×10 mL), the combined
organic layers were dried with anhydrous sodium sulfate. The
solvent was removed in vacuo, the products were isolated by
silica gel column chromatography (silica gel 40—100 μm;
elution with ethyl acetate—petroleum ether gradient 1 : 20→1 : 10).
The retention factor values (Rf) were determined using Silufol
precoated plates eluting with ethyl acetate—petroleum ether
(1 : 10). The microanalysis data for isoxazoles 2d and 4c are
given in our previous work.32 1H and 13C NMR spectral data for
isoxazoles 2a—e and 4a—d are summarized in Table 1.
Reaction involving 1,1ꢀdibromoꢀ2ꢀphenylcyclopropane (1a)
(0.550 g, 2.0 mmol) afforded 1,1ꢀdibromoꢀ2ꢀ(bromophenyl)ꢀ
cyclopropane (3) (yield 0.057 g (8%)), 5ꢀbromoꢀ3ꢀphenylisoxꢀ
azole (2a) (yield 0.134 g (30%), creamy crystals, m.p. 49—51 °C
(cf. Ref. 20: m.p. 48—50 °C), Rf 0.40), and 5ꢀbromoꢀ3ꢀ(4ꢀ
bromophenyl)isoxazole (2b) (yield 0.049 g (8%), Rf 0.58).
Reaction involving 1,1ꢀdibromoꢀ2ꢀ(4ꢀbromophenyl)cycloꢀ
propane (1b) (0.71 g, 2.0 mmol) afforded 5ꢀbromoꢀ3ꢀ(4ꢀbromoꢀ
phenyl)isoxazole (2b) (yield 0.212 g (35%), creamy crystals,
Rf 0.58, m.p. 128—129 °C (cf. Ref. 12: m.p. 127—128 °C)) and
4,5ꢀdibromoꢀ3ꢀ(4ꢀbromophenyl)isoxazole (4a) (yield 0.344 g
(45%), Rf 0.78, m.p. 98 °C).
Compound 5. H NMR (CDCl3), δ: 2.05 (dd, 1 H, CH2,
2J = 8.0 Hz, 3J = 8.2 Hz); 2.23 (dd, 1 H, CH2, 2J = 10.2 Hz,
3J = 8.0 Hz); 2.95 (dd, 1 H, CH, 2J = 10.2 Hz, 3J = 8.2 Hz); 7.19
(d, 1 H, arom., 4J = 2.3 Hz); 7.34 (dd, 1 H, arom., 3J = 8.4 Hz,
4J = 2.3 Hz); 7.54 (d, 1 H, arom., 3J = 8.4 Hz). 13C NMR
(CDCl3), δ: 26.6 (CBr2), 27.5 (CH2), 36.8 (CH), 121.1 (CBr),
125.8 (CBr), 132.2 (CHAr), 132.6 (CHAr), 134.0 (CHAr), 139.1
(CAr). Found (%): C, 24.91; H, 1.35. C9H6Br4. Calculated (%):
C, 24.88; H, 1.38.
Compound 4d. MS (EI, 70 eV), m/z (Irel (%)): 379 [M]+ (7),
381 (15), 383 (16), 385 (8); 300 [M – Br]+ (38), 302 (84), 304 (48);
272 [M – Br – CO]+ (8), 274 (16), 276 (8); 221 [M – 2 Br]+
(78), 223 (88); 155 [C6H4Br]+ (19), 157 (19); 114 (58) [M – 3 Br –
– CO]+, 102 [C6H4CN]+ (34), 75 (70) [C6H3]+, 50 (100).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 15ꢀ03ꢀ04260)
and the Presidium of the Russian Academy of Sciences
(Basic Research Program "Development of Synthetic Proꢀ
cedures towards Chemical Substances and Design of Novel
Materials").
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