Gem-dichloro(alkyl)cyclopropanes in reactions with NOCl?2SO 3: Synthesis of alkyl-5-chloroisoxazoles

Article abstract of DOI:10.1007/s11172-011-0053-7

Nitrosation of gem-dichloro(alkyl)cyclopropanes with the complex NOCl?2SO₃ gave regioisomeric alkyl-5-chloroisoxazoles in high yields; a similar reaction with 1,2-bis(gem-dichlorocyclopropyl)ethane afforded the corresponding bis(5-chloroisoxazoles). The reactivities of gem-dichlorobicyclo[n.1.0]alkanes depend on their spatial structures, sharply decreasing with an increase in the number of the methylene units in the bicyclic molecule.

Full text of DOI:10.1007/s11172-011-0053-7

Russian Chemical Bulletin, International Edition, Vol. 60, No. 2, pp. 328—333, February, 2011
328
gemꢀDichloro(alkyl)cyclopropanes in reactions with NOCl•2SO3:
synthesis of alkylꢀ5ꢀchloroisoxazoles
N. V. Zyk,a O. B. Bondarenko,a A. Yu. Gavrilova,a A. O. Chizhov,b and N. S. Zefirova
aDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119991 Moscow, Russian Federation.
Fax: +7 (495) 939 4652. Eꢀmail: bondarenko@org.chem.msu.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328
Nitrosation of gemꢀdichloro(alkyl)cyclopropanes with the complex NOCl•2SO3 gave reꢀ
gioisomeric alkylꢀ5ꢀchloroisoxazoles in high yields; a similar reaction with 1,2ꢀbis(gemꢀdiꢀ
chlorocyclopropyl)ethane afforded the corresponding bis(5ꢀchloroisoxazoles). The reactivities
of gemꢀdichlorobicyclo[n.1.0]alkanes depend on their spatial structures, sharply decreasing
with an increase in the number of the methylene units in the bicyclic molecule.
Key words: gemꢀdichloro(alkyl)cyclopropanes, nitrosation, the complex NOCl•2SO3, alkylꢀ
5ꢀchloroisoxazoles, synthesis.
Addition of carbenes to olefins is a common route to
The objects of our present study included cyclopropꢀ
anes and biscyclopropanes containing a linear alkyl subꢀ
stituent and a number of biꢀ and tricycloalkanes containꢀ
ing one or two threeꢀmembered rings.
We found that 2ꢀ(nꢀbutyl)ꢀ1,1ꢀdichloroꢀ (1a) and
1,1ꢀdichloroꢀ2ꢀ(nꢀhexyl)cyclopropanes (1b) react with
NOCl•2SO3 in CH2Cl2 with a 100% conversion to give
mixtures of isomeric 3ꢀalkylꢀ (2a,b) and 4ꢀalkylꢀ5ꢀchloroꢀ
isoxazoles (3a,b) in high yields (2a : 3a = 1 : 1.5; 2b : 3b =
= 1 : 1.2) (Scheme 1). The first step of this transformation
is an electrophilic attack of the nitrosating agent at the
cyclopropane ring with cleavage of one of its bonds.4,6
cyclopropanes.1 Generation of dihalocarbenes under the
conditions of phaseꢀtransfer catalysis with their subsequent
cycloaddition to olefins has offered a nearly complete soluꢀ
tion of the problem of cyclopropane ring formation.2 Conꢀ
siderable achievements in this area of organic chemistry
have been made by involving various olefins (including
structurally exotic ones2,3) in this reaction, which subꢀ
stantially extended its synthetic scope. As a result, a large
number of various gemꢀdihalocyclopropanes are available
for organic chemists. At present, the study of their chemiꢀ
cal properties for comprehensive use of their synthetic poꢀ
tential in organic synthesis is a problem of prime imporꢀ
tance. gemꢀDihalocyclopropanes have been employed3 as
starting materials for the synthesis of both cyclopropane
derivatives and organic compounds of other classes by
means of transformation of the cyclopropane ring. For
instance, it has been reported4 that gemꢀdihalo(aryl)cycloꢀ
propanes react with nitrosonium tetrafluoroborate to give
isoxazoles. However, the possibility of obtaining isoxazoles
from gemꢀdihalo(alkyl)cyclopropanes has been demonꢀ
strated only with 7,7ꢀdichloronorcarane as an example;
the yield of the corresponding isoxazole was 43%.
Scheme 1
Taking into account that various gemꢀdihalocycloproꢀ
panes are easily accessible and that isoxazoles are of pracꢀ
tical value as compounds with a broad spectrum of biologꢀ
ical activity, we studied the nitrosation of gemꢀdichloroꢀ
(alkyl)cyclopropanes under the action of NOCl•2SO3.
Earlier,5,6 this complex has been successfully employed
for the synthesis of isoxazolines from arylcyclopropanes.
R = Bun (a), nꢀC6H13 (b)
i. NOCl•2SO3, CH2Cl2.
Regioisomers 2a and 3a and regioisomers 2b and 3b
were separated by column chromatography and characꢀ
1
terized using H and 13C NMR spectroscopy and mass
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 321—326, February, 2011.
1066ꢀ5285/11/6002ꢀ328 © 2011 Springer Science+Business Media, Inc.

Alkylꢀ5ꢀchloroisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
329
Table 1. 13C NMR spectra (CDCl3) of substituted 5ꢀchloroisoxazoles
Compound
δ
C(3)
С(4)
С(5)
The other C atoms
2а
2b
165.9
166.3
100.8
101.0
154.2
154.2
13.7 (Me), 22.2 (CН2), 26.1 (CН2), 30.0 (CН2)
14.0 (Me), 22.5 (CН2), 26.4 (CН2), 27.9 (CН2),
28.7 (CН2), 31.4 (CН2)
3a
3b
152.5
152.8
113.9
114.1
150.8
150.8
13.7 (Me), 21.7 (CН2), 22.1 (CН2), 31.2 (CН2)
14.0 (Me), 22.0 (CН2), 22.5 (CН2), 28.6 (CН2),
29.0 (CН2), 31.4 (CН2)
5
6
164.9
152.7
101.2
112.9
154.7
151.5
25.5 (CН2), 26.7 (CН2), 28.6 (CН2), 29.8 (CH),
60.8 (CCl2)
21.2 (CН2), 26.6 (CН2), 29.8 (CH), 29.9 (CH2),
60.7 (CCl2)
7
8*
164.2
101.2
152.6
155.1
152.4
151.9
145.1
148.7
149.3
24.5 (2 CH2)
20.3 (CH2), 26.0 (CH2)
164.0 (RC=N)
152.6 (HC=N)
152.4
176.1
162.7
101.1 (=CH)
112.2 (=CR)
112.0
119.6
110.0
9
21.9 (2 CH2)
11a
11b
11c
21.4 (CH2), 24.4 (CH2), 30.5 (CH2)
18.5 (CH2), 21.9 (CH2) 22.0 (2 CH2)
23.5 (CH2), 27.0 (CH2), 27.9 (CH2), 28.3 (CH2),
31.8 (CH2)
167.0
114.8
14
164.7
112.8
151.4
19.6 (CH2), 22.9 (CH2), 23.5 (CH2), 23.7 (CH2),
33.1 (CH), 33.3 (CH), 64.6 (CCl2)
* For assignment of the signals for the quaternary C atoms in isomer 8, the δC values of the isoxazole ring in compounds
2, 3, 7, and 9 were taken into account.
spectrometry. The structure of the isomers was determined
the nitrosonium cation preferably attacks the more steriꢀ
cally accessible site of the cyclopropane ring (Scheme 2).
1
and the signals for the isomers were assigned from the H
and 13C NMR spectra (Table 1).
1
For instance, in the H NMR spectrum of isoxazole
Scheme 2
2a, the signal for the H atom of the heterocycle (CH=CCl)
appears at δ 6.02. The 13C NMR spectrum contains sigꢀ
nals for the C(4), C(5), and C(3) atoms of the isoxazole
ring at δ 100.8, 154.2, and 165.9, respectively (see Table 1).
In addition, the two lowerꢀfield signals are quaternary;
this confirms the attachment of the nꢀbutyl substituent to
the C(3) atom of the heterocycle.
1
The H NMR spectrum of isomer 3a shows a signal
for the H atom of the heterocycle (HC=N) at δ 8.15;
in the 13C NMR spectrum, the signals for the C(4),
C(5), and C(3) atoms of the isoxazole ring appear at
δ 113.9, 150.8, and 152.5, respectively. Since the signal
for the C(4) atom is quaternary, the butyl substituent is
attached to this atom. Note that the signals attributed to
the C(4) and C(3) atoms in isomer 3a are shifted downꢀ
field and upfield, respectively, by 13 ppm compared to
those for isomer 2a.
Thus, the nitrosation of 2ꢀalkylꢀ1,1ꢀdichlorocycloꢀ
propanes 1a,b with NOCl•2SO3 is not regioselective,
yielding isomeric 5ꢀchloroisoxazoles 2a,b and 3a,b. An attack
of the electrophilic species NO+ results in cleavage of both
the C(1)—C(2) and C(1)—C(3) bonds of the cyclopropane
ring. The latter pathway is slightly preferred, which follows
from the somewhat higher fractions of C(3)ꢀunsubstituted
isoxazoles 3a,b in mixtures with their isomers 2a,b; i.e.,
We also studied nitrosation of 1,2ꢀbis(2,2ꢀdichloroꢀ
cyclopropyl)ethane (4) with NOCl•2SO3 and found that
the reaction proceeds through the opening of one or both
of the cyclopropane rings and affords isomeric monoꢀ (5, 6)
and bisisoxazoles (7—9) in a total yield of 85% (Scheme 3).
The isoxazoles were separated by column chromatoꢀ
graphy on silica gel; their structures were determined using
1H and 13C NMR spectroscopy. The signals for the proꢀ
tons of the cyclopropane ring in isomer 6 were assigned

330
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
Zyk et al.
Scheme 3
that bisisoxazole 8 is mainly obtained from isomer 6 (i.e.,
the latter is more reactive than isomer 5).
However, the presence of one isoxazole ring generally
does not prevent the formation of the second ring in comꢀ
pounds 7—9.
We studied nitrosation of polycyclic gemꢀdichloroꢀ
cyclopropanes with gemꢀdichlorobicyclo[n.1.0]alkanes as
examples. We found that the nitrosation of bicycloalkanes
10a—d gives 5ꢀchloroꢀ3,4ꢀcycloalkylisoxazoles 11a—d.
The yields of the isoxazoles from 6,6ꢀdichlorobicycloꢀ
[3.1.0]hexane 10a and 7,7ꢀdichlorobicyclo[4.1.0]heptane
10b are high, though noticeably decreasing with an inꢀ
crease in the number of methylene units in the starting
bicycloalkane (Scheme 4).
Scheme 4
i. NOCl•2SO4, CH2Cl.
Compound
m
Yield (%)
10,11
of compound 11
a
b
c
d
0
1
2
3
90
70
30
10
The yield of isoxazole 11c from 8,8ꢀdichlorobicycloꢀ
[5.1.0]octane 10c was 30%; the unreacted residue of comꢀ
pound 10c was recovered intact. Cyclopropane 10c was
also inert under other reaction conditions (NOCl•2SO3,
CH3NO2, 20 °C, 24 h or NOBF4, CH3CN, 20 °C, 24 h).
In the case of 9,9ꢀdichlorobicyclo[6.1.0]nonane 10d, the
yield of isoxazole 11d was only 10%; however, the conꢀ
sumption of compound 10d was considerable (up to 50%).
The possibility of the formation of two isoxazole fragꢀ
ments in one molecule prompted us to study the nitrosaꢀ
tion of tricycloalkanes 12 and 13.
i. NOCl•2SO3, CH2Cl2.
from the coupling constants found in a selective homoꢀ
decoupling experiment with irradiation of the H NMR
1
signals at δ 1.13, 1.83, and 2.64 (see Experimental).
Note that the ratio of monoꢀ (5, 6) and dinitrosation
products (7—9) depends on the ratio of the starting reꢀ
agents. For instance, when the molar ratio 4 : NOCl•2SO3
is 1 : 2 (20 °C, 24 h), the ratio of the isoxazoles in the final
mixture is 5 : 6 : 7 : 8 : 9 = 34 : 27 : 5 : 19 : 15 (1H NMR);
compound 4 (9%) is recovered. For 4 : NOCl•2SO3 = 1 : 4
(20 °C, 120 h), the ratio of the same isoxazoles is
26 : 7 : 11 : 32 : 24. Note that isomers 7 and 9 can be obꢀ
tained only from isoxazoles 5 and 6, respectively, while
isomer 8 can be a product from both.
Cyclopropylethylisoxazoles 5 and 6 were isolated in
the individual state by column chromatography. Their reꢀ
actions with an excess of NOCl•2SO3 gave bisisoxazoles
7 and 8 (from 5) and 8 and 9 (from 6) in quantitative
yields: 7 : 8 = 1.4 : 1 and 8 : 9 = 1 : 0.8 (1H NMR).
An analysis of the isomer ratios in mixtures of isoxꢀ
azoles 5—9, as well as the preferential formation of 4ꢀalkylꢀ
5ꢀchloroisoxazoles (isomers 3a,b, see Scheme 1), suggests
Insofar as bicyclohexane 10a is very highly reactive,
3,3,7,7ꢀtetrachlorotricyclo[4.1.0.02,4]heptane (12) could
be expected to be also reactive in nitrosation. However,
the latter was inert under standard reaction conditions
(NOCl•2SO3, CH2Cl2, 20 °C, 24 h). Nor did it react with
NOCl•2SO3 in boiling CH2Cl2 or chloroform for 8 and
70 h, respectively; compound 12 was fully recovered from
the reaction mixture.

Alkylꢀ5ꢀchloroisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
331
5,5,10,10ꢀTetrachlorotricyclo[7.1.0.04,6]decane (13) as
a 9 : 1 mixture of cisꢀ and transꢀisomers (1H NMR) was
kept with a twofold excess of NOCl•2SO3 in CH2Cl2 at
25—30 °C for five days. The degree of its conversion into
isoxazole 14 was 75% (1H NMR), only one cyclopropane
ring being involved (Scheme 5). The starting compound
13 was recovered in 15% yield (cis : trans = 1 : 2). By exꢀ
tending the reaction time to 55 days, we produced no
effect on the composition of the reaction mixture or the
yield of isoxazole 14.
5% yield; its structure and molecular formula were deterꢀ
mined from 1H and 13C NMR, IR, and mass spectra and
elemental analysis data.
Scheme 6
Scheme 5
i. NOCl•2SO3 (2 equiv.), CH2Cl2, 25—30 °C, 5 days.
To sum up, we demonstrated that the nitrosation of
2ꢀalkylꢀ1,1ꢀdichlorocyclopropanes with NOCl•2SO3 afꢀ
fords regioisomeric 3ꢀ and 4ꢀalkylꢀ5ꢀchloroisoxazoles in
high yields; bis(5ꢀchloroisoxazolyl) derivatives were obꢀ
tained from 1,2ꢀbis(dichlorocyclopropyl)ethane. The
nitrosation of gemꢀdichlorobiꢀ and ꢀtricycloalkanes conꢀ
taining the cyclopropane ring is regioselective; however,
the yields of the resulting isoxazoles largely depend on the
spatial structure of the substrate molecule.
The lower reactivities of tricycloꢀ (12, 13) and some
bicycloalkanes (10c,d) are probably due to their spatial
structures. Tricycloheptane 12 obtained from cyclopentaꢀ
diene by the Makosza reaction is known to exist as one
stereoisomer with the antiꢀconfiguration of the cycloproꢀ
pane rings*. Apparently, the antiꢀarrangement of the cycloꢀ
propane fragments additionally shielded by the Cl atoms
makes the reactive site less accessible for the nitrosating
agent. As for tricyclodecane 13, it has been reported9 to be
a 3 : 1 mixture of cisꢀ and transꢀisomers.
Experimental
The steric factor may be another plausible reason for
the lower reactivities of larger bicycloalkanes 10c,d. Apꢀ
parently, the molecule takes the most favorable conforꢀ
mation, in which the reactive site (the cyclopropane ring)
is shielded by the carbon framework.
1
H and 13C NMR spectra were recorded on VarianꢀXRꢀ400
and Bruker Avanceꢀ400 instruments (400 (1H) and 100 MHz
13C)) in CDCl3 with HMDS as the internal standard. IR specꢀ
(
tra were recorded on a URꢀ20 instrument (Nujol or thin film).
Mass spectra were measured on a Finnigan MAT SSQ 7000
GCꢀMS spectrometer (ionizing energy 70 eV, OVꢀ1 quartz capꢀ
illary column (25 m), programmed temperature rise from 70 °C
(2 min) to 280 °C (10 min) at a heating rate of 20 deg min–1) and
a Finnigan MAT ITDꢀ700 GCꢀMS spectrometer (Varian 3400
chromatograph, HPꢀ101 quartz capillary column (25 m), proꢀ
grammed temperature rise from 80 °C (1 min) to 290 °C (10 min)
at a heating rate of 10 deg min–1). For chlorineꢀcontaining ions,
the m/z ratios are cited for the 35Cl isotope. Melting points were
determined in open capillaries placed on a heating block. The
course of the reactions was monitored, and the purity of the
compounds was checked, by TLC on SilufolꢀUV plates; spots
were visualized under UV light. All the solvents used were puriꢀ
fied and dehydrated according to standard procedures.14
gemꢀDichlorocyclopropanes (1a,b, 4, 10a—d, 12, and 13)
were prepared from appropriate alkenes by the Makosza reacꢀ
tion.8 Their physicochemical constants agree with the literature
data.8,9,15—17 The 1H and 13C NMR spectra of the starting reꢀ
agents that are unavailable from the literature are given in Table 2.
The 13C NMR spectra of the 5ꢀchloroisoxazoles obtained are
given in Table 1.
Note that the opening of the cyclopropane ring in
bicyclo[n.1.0]alkanes can occur by cleavage of both the
exocyclic and endocyclic C—C bonds. It is known that
the decrease in the number n of methylene units in
bicyclo[n.1.0]alkanes makes the endocyclic bond more
liable to cleavage because of increased strain in the moleꢀ
cule; this reaction pathway usually becomes appreciable
for bicyclo[3.1.0]hexane.10—13 In our case, the nitrosation of
bicycloalkanes was regioselective, with cleavage of the exoꢀ
cyclic bond only. The intermediate cation A (Scheme 6)
can be stabilized either by cyclization that results from
a nucleophilic attack of the O atom of the nitroso group
and finally leads to isoxazole 11a or by abstraction of the
C(2)H proton with simultaneous isomerization of the niꢀ
troso group into an oxime one. Indeed, in the case of
bicyclohexane 10a, we isolated unsaturated oxime 15 in
* The spectroscopic characteristics of compound 12 are in full
agreement with the literature data.7,8

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Zyk et al.
Table 2. 1H and 13C NMR spectra (CDCl3) of compounds 1a,b, 10a—d, and 13*
Compound
NMR, δ (J/Hz)
1H
13С
1a
0.96 (t, 3 Н, Me, 3J = 7.0); 1.06 (dist.t,
14.1 (Me), 22.4 (CH2), 26.8 (CH2), 30.1 (CH),
30.81 (CH2), 30.84 (CH2), 61.5 (СCl2)
3
1 Н, J = 4.4); 1.42 (quint, 2 Н, СН2,
3J = 7.0); 1.45—1.65 (m, 6 Н)
1b
0.92 (t, 3 Н, Me, 3J = 6.8); 1.05 (m, 1 Н);
1.33 (m, 6 Н, 3 СН2); 1.44—1.64 (m, 6 Н)
1.63—1.80 (m, 2 Н); 1.95—2.10 (m, 4 Н);
2.10—2.13 (m, 2 Н)
14.1 (Me), 22.6 (CH2), 26.8 (CH2), 28.6 (CH2),
29.0, 30.4 (CH2), 30.9, 31.8, 61.6 (СCl2)
25.1 (CH2), 27.7 (2 CH2), 38.2 (2 CH),
68.2 (СCl2)
18.9 (2 CH2), 20.2 (2 CH2), 25.8 (2 CH),
67.4 (СCl2)
10a
10b
10c
1.22 (m, 2 Н); 1.34 (m, 2 Н); 1.63—1.76
(m, 4 Н); 1.96 (m, 2 Н)
1.10—1.40 (m, 5 Н); 1.66 (m, 2 Н);
26.5 (2 CH2), 28.3 (2 CH2), 32.3 (2 CH),
33.9 (CH2), 68.2 (СCl2)
2
1.82 (m, 2 Н); 1.90 (dm, 1 Н, J = 13.5);
2.15 (m, 1 Н); 2.19 (m, 1 Н)
10d
1.22 (m, 2 Н); 1.34—1.52 (m, 6 Н);
1.55—1.71 (m, 4 Н); 2.05 (dm, 2 Н,
2J = 14.1)
23.2 (2 CH2), 26.3 (2 CH2), 28.0 (2 CH),
32.4 (2 CH2), 65.2 (СCl2)
13ꢀcis
13ꢀtrans
1.63 (m, 4 Н); 1.74 (m, 4 Н); 2.21 (m, 4 Н)
1.25 (m, 4 Н); 1.73 (m, 4 Н); 2.30 (m, 4 Н)
21.3 (4 CH2), 31.0 (4 CH), 66.0 (СCl2)
21.9 (4 CH2), 34.4 (4 CH), 65.3 (СCl2)
* The 1H and 13C NMR spectra of compounds 4, 12, and cisꢀ13 have been cited in Refs 8 and 9.
Nitrosation of gemꢀdichlorocyclopropanes with the complex
(m, 6 H, 3 CH2); 1.65 (quint, 2 H, CH2, 3J = 7.6 Hz); 2.64 (t, 2 H,
NOCl•2SO3 (general procedure). An appropriate gemꢀdichloroꢀ
cyclopropane (1.0 mmol) in CH2Cl2 (2 mL) was added at 20 °C
to a suspension of NOCl•2SO3 (1.2—1.5 mmol*) in CH2Cl2
(10 mL). The reaction mixture was stirred for 24 h, neutralized
with NaHCO3, and washed with water. Organic material was
extracted from the aqueous fractions with CH2Cl2 (3×10 mL).
The organic extracts were combined, dried with Na2SO4, and
concentrated. The products were isolated by column chromaꢀ
tography on SiO2 (40—100 μm, AcOEt—light petroleum as an
eluent).
CH2, 3J = 7.6 Hz); 6.03 (s, 1 H, CH=). MS, m/z (Irel (%)): 188
[M + H]+ (100), 152 [M – Cl]+ (24), 130 [M – Bun]+ (4), 117
[M + H – Amn]+ (22), 108 (4), 96 [M + H – Cl – Bun]+ (11),
82 (15), 68 (7), 55 (11).
5ꢀChloroꢀ4ꢀnꢀhexylisoxazole (3b). Yield 42%, colorless oil
with a pungent odor. Rf 0.55 (AcOEt—light petroleum, 1 : 10).
3
1H NMR, δ: 0.89 (dist.t, 3 H, Me, J = 6.9 Hz); 1.30 (m, 6 H,
3 CH2); 1.55 (quint, 2 H, CH2, 3J = 7.6 Hz); 2.38 (t, 2 H, CH2,
3J = 7.6 Hz); 8.16 (s, 1 H, CH=). MS, m/z (Irel (%)): 188
[M + H]+ (100), 152 [M – Cl]+ (37), 124 (13), 116 [M – Amn]+
(10), 95 [M – Cl – Bun]+ (25), 82 (35), 67 (18), 55 (50). 2b + 3b.
Found (%): C, 57.65; H, 7.54; N, 7.67. C9H14ClNO. Calculatꢀ
ed (%): C, 57.60; H, 7.47; N, 7.47.
3ꢀnꢀButylꢀ5ꢀchloroisoxazole (2a). Yield 36%, colorless oil
with a pungent odor. Rf 0.60 (AcOEt—light petroleum, 1 : 15).
3
1H NMR, δ: 0.97 (t, 3 H, Me, J = 7.4 Hz); 1.42 (sextet, 2 H,
CH2, 3J = 7.4 Hz); 1.65 (quint, 2 H, CH2, 3J = 7.6 Hz); 2.66
(t, 2 H, CH2, 3J = 7.6 Hz); 6.02 (s, 1 H, CH=). MS, m/z (Irel (%)):
5ꢀChloroꢀ3ꢀ[2ꢀ(2,2ꢀdichlorocyclopropꢀ1ꢀyl)ethyl]isoxazole
(5). Yield 22%, colorless oil. Rf 0.69 (AcOEt—light petroleum,
+
1
159 [M]+ (1), 144 [M – Me] (0.6), 130 [M – Et]+ (13), 124
[M – Cl]+ (25), 117 [M – C3H6]+ (100), 96 [M – Cl – Et]+
(13), 82 [M – Cl – C3H6]+ (15), 68 [C3H2NO]+ (40), 55 (20),
44 (42), 41 (75).
1 : 6). H NMR, δ: 1.14 (m, 1 H); 1.65 (m, 2 H); 1.94 (m, 2 H,
•
CH2); 2.85 (dt, 1 H, CH2, 2J = 14.8 Hz, 3J = 7.5 Hz), 2.89 (dt, 1 H,
CH2, 2J = 14.8 Hz, 3J = 7.5 Hz); 6.10 (s, 1 H). MS, m/z (Irel (%)):
240 [M + H]+ (3), 204 [M – Cl]+ (3), 168 [M – Cl –
– HCl]+ (1), 116 [C3HNOClCH2]+ (4), 108 (100). Found (%):
C, 40.09; H, 3.20; N, 5.69. C8H8Cl3NO. Calculated (%):
C, 39.92; H, 3.33; N, 5.82.
4ꢀnꢀButylꢀ5ꢀchloroisoxazole (3a). Yield 54%, colorless oil
with a pungent odor. Rf 0.40 (AcOEt—light petroleum, 1 : 15).
3
1H NMR, δ: 0.97 (t, 3 H, Me, J = 7.4 Hz); 1.38 (sextet, 2 H,
CH2, 3J = 7.4 Hz); 1.57 (quint, 2 H, CH2, 3J = 7.6 Hz); 2.40
(t, 2 H, CH2, 3J = 7.6 Hz); 8.15 (s, 1 H, CH=). MS, m/z (Irel (%)):
5ꢀChloroꢀ4ꢀ[2ꢀ(2,2ꢀDichlorocyclopropꢀ1ꢀyl)ethyl]isoxazole
(6). Yield 22%, colorless oil. Rf 0.58 (AcOEt—light petroleum,
1 : 6). 1H NMR, δ: 1.13 (t, 1 Ha, 2Ja,b ≈ Ja,c = 6.8—7.3 Hz); 1.57
159 [M]+ (39), 144 [M – Me]+ (3), 130 [M – Et]+ (23), 124
•
[M – Cl]+ (57), 116 [M – Pr]+ (100), 96 [M – Cl – Et]+ (33), 82
[M – Cl – C3H6]+ (18), 68 [C3H2NO]+ (18), 55 (24), 41 (38).
2a + 3a. Found (%): C, 52.72; H, 6.22; N, 8.62. C7H10ClNO.
Calculated (%): C, 52.66; H, 6.27; N, 8.78.
(ddt, 1 Hc, Ja,c = 7.3 Hz, Jb,c = 10.3 Hz); 1.64 (dd, 1 Hb,
2Ja,b = 6.8 Hz, 3Jb,c = 10.3 Hz); 1.83 (q, 2 H, C(2)H2, 3J = 7.3 Hz);
2.61 and 2.66 (both dt, 1 H each, C(1)H2, 2J = 14.9 Hz, 3J = 7.3 Hz);
8.24 (s, 1 H). MS, m/z (Irel (%)): 240 [M + H]+ (2), 204 [M – Cl]+
(17), 175 [M – NOCl]+ (46), 142 (25), 115 [C3NOClCH2]+
(59), 107 (100), 86 (56), 79 (85). Found (%): C, 39.87; H, 3.45;
N, 5.75. C8H8Cl3NO. Calculated (%): C, 39.92; H, 3.33; N, 5.82.
5ꢀChloroꢀ3ꢀ[2ꢀ(5ꢀchloroisoxazolꢀ3ꢀyl)ethyl]isoxazole (7),
m.p. 41—42 °C. Rf 0.56 (AcOEt—light petroleum, 1 : 3).
1H NMR, δ: 3.08 (s, 4 H, 2 CH2), 6.09 (s, 2 H, CH=). MS, m/z
3
3
5ꢀChloroꢀ3ꢀnꢀhexylisoxazole (2b). Yield 35%, colorless oil
with a pungent odor. Rf 0.74 (AcOEt—light petroleum, 1 : 10).
1H NMR, δ: 0.90 (dist.t, 3 H, Me, 3J = 6.8 Hz); 1.28—1.42
* For cyclopropanes 4 and 13, the molar ratios of cyclopropane
to NOCl•2SO3 are 1 : 2 and 1 : 4.

Alkylꢀ5ꢀchloroisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
333
(Irel (%)): 233 [M + H]+ (0.4), 197 [M – Cl]+ (7), 169 [M – Cl –
– CO]+ (100), 133 (36), 106 (27), 78 (18), 67 (32). Found (%):
C, 41.10; H, 2.69; N, 12.13. C8H6Cl2N2O2. Calculated (%):
C, 41.20; H, 2.58; N, 12.02.
5ꢀChloroꢀ3ꢀ[2ꢀ(5ꢀchloroisoxazolꢀ4ꢀyl)ethyl]isoxazole (8),
colorless oil. Rf 0.50 (AcOEt—light petroleum, 1 : 3). 1H NMR,
δ: 2.83 (t, 2 H, 3J = 7.3 Hz); 2.94 (t, 2 H, 3J = 7.3 Hz); 6.04 (s, 1 H,
CH=); 8.21 (s, 1 H, CH=). MS, m/z (Irel (%)): 233 [M + H]+
(0.3), 197 [M – Cl]+ (65), 169 [M – Cl – CO]+ (100), 142 (63),
116 [C3HNOClCH2]+ (25), 80 [C3NOCH2]+ (30), 63 (21).
Found (%): C, 41.08; H, 2.37; N, 12.19. C8H6Cl2N2O2. Calcuꢀ
lated (%): C, 41.20; H, 2.58; N, 12.02.
(quint, 2 H, CH2, 3J = 7.6 Hz); 2.73 (t, 2 H, CH2, 3J = 7.6 Hz);
2.79 (t, 2 H, CH2, 3J = 7.6 Hz); 8.69 (br.s, 1 H, OH). 13C NMR,
δ: 20.8, 29.7, 35.2, 134.0 (C=); 151.0 (=CCl2); 160.1 (C=N).
MS, m/z (Irel (%)): 179 [M]+• (30), 163 (5), 134 (10), 108 (23),
89 (100), 80 (93), 73 (42), 63 (35), 54 (84). Found (%): C, 40.10;
H, 4.16; N, 7.57. C6H7Cl2NO. Calculated (%): C, 40.00; H, 3.90;
N, 7.80.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ00707ꢀa)
and the Presidium of the Russian Academy of Sciences
(Basic Research Program "Development of the Methods
for the Synthesis of Chemical Compounds and Creation
of Novel Materials").
5ꢀChloroꢀ4ꢀ[2ꢀ(5ꢀchloroisoxazolꢀ4ꢀyl)ethyl]isoxazole (9),
m.p. 57—58 °C. Rf 0.35 (AcOEt—light petroleum, 1 : 3).
1H NMR, δ: 2.69 (s, 4 H, 2 CH2); 8.16 (s, 2 H, CH=). MS, m/z
(Irel (%)): 232 [M]+• (10), 116 [C3HNOClCH2]+ (100), 79 (95),
61 (23), 44 (30), 36 (57). Found (%): C, 41.08; H, 2.63; N, 12.15.
C8H6Cl2N2O2. Calculated (%): C, 41.20; H, 2.58; N, 12.02.
3ꢀChlorocyclopent[c]isoxazole (11a). Yield 90%, colorless oil
with a pungent odor. Rf 0.51 (AcOEt—light petroleum, 1 : 5).
IR, ν/cm–1: 2970, 2880, 1650, 1400, 1125, 1030. 1H NMR, δ:
References
1. W. Kirmse, Carbene Chemistry, Academic Press, New York,
1964.
2. W. P. Weber, G. W. Gokel, Phase Transfer Catalysis in Orꢀ
ganic Synthesis, Springer, Berlin, 1977, 280 pp.
3. N. S. Zefirov, I. V. Kazimirchik, K. L. Lukin, Tsikloprisoꢀ
edinenie dikhlorkarbena k olefinam [Cycloaddition of Diꢀ
chlorocarbene to Olefins], Nauka, Moscow, 1985, 152 pp.
(in Russian).
3
3
2.50 (quint, 2 H, J = 7.2 Hz); 2.63 (t, 2 H, J = 7.2 Hz); 2.83
(t, 2 H, J = 7.2 Hz). MS, m/z (Irel (%)): [M]+ 143 (21), 115
[M – C2H4]+ (14), 108 [M – Cl]+ (18), 80 [M – Cl – C2H4]+ (62),
63 (16), 53 (100). Found (%): C, 50.01; H, 4.25; N, 9.89.
C6H6ClNO. Calculated (%): C, 50.17; H, 4.18; N, 9.76.
3
•
3ꢀChloroꢀ4,5,6,7ꢀtetrahydrobenz[c]isoxazole (11b). Yield
70%, m.p. 36 °C (cf. Ref. 4: 34.2—35.8 °C). Rf 0.62 (AcOEt—light
petroleum, 1 : 6). IR, ν/cm–1: 2960, 2940, 2875, 1630, 1450,
4. S.ꢀT. Lin, S.ꢀH. Kuo, F.ꢀM. Yang, J. Org. Chem., 1997,
62, 5229.
5. O. B. Bondarenko, A. Yu. Gavrilova, L. G. Saginova, N. V.
Zyk, N. S. Zefirov, Izv. Akad. Nauk, Ser. Khim., 2003, 741
[Russ. Chem. Bull., Int. Ed., 2003, 52, 778].
6. O. B. Bondarenko, A. Yu. Gavrilova, L. G. Saginova, N. V.
Zyk, Zh. Org. Khim., 2009, 45, 230 [Russ. J. Org. Chem.
(Engl. Transl.), 2009, 45, 218].
7. E. V. Dehmlow, Tetrahedron, 1972, 28, 175.
8. W. Kuhn, H. Marschall, P. Weyerstahl, Chem. Ber., 1977,
110, 1564.
9. L. F. Fieser, D. H. Sachs, J. Org. Chem., 1964, 29, 1113.
10. R. T. LaLonde, M. A. Tobias, J. Am. Chem. Soc., 1964,
86, 4068.
11. R. T. LaLonde, J. J. Batelka, Tetrahedron Lett., 1964, 5, 445.
12. F. R. Jensen, D. B. Patterson, S. E. Dinizo, Tetrahedron
Lett., 1974, 15, 1315.
13. P. H. Atkinson, R. C. Camble, G. Dixon, W. I. Noall, P. S.
Rutledge, P. D. Woodgate, J. Chem. Soc., Perkin Trans. 1,
1977, 230.
14. A. J. Gordon, R. A. Ford, The Chemist´s Companion: A Handꢀ
book of Practical Data, Techniques, and References, Wiley,
New York, 1972, 537 pp.
15. W. E. von Doering, A. K. Hoffmann, J. Am. Chem. Soc.,
1954, 76, 6162.
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1
1420, 1215, 1160, 765. H NMR, δ: 1.70 (m, 4 H, 2 CH2); 2.37
(t, 2 H, CH2, 3J = 6.3 Hz); 2.65 (t, 2 H, CH2, 3J = 6.3 Hz). MS,
m/z (Irel (%)): 157 [M]+ (100), 130 [M – C2H3]+ (36), 122
•
[M – Cl]+ (36), 115 [M – C3H6]+ (30), 100 (40), 94 [M – Cl –
– C2H4]+ (11), 80 [M – Cl – C3H6]+ (55), 67 [C3HNO]+ (3).
3ꢀChlorocyclohept[c]isoxazole (11c). Yield 30%, Rf 0.56
(AcOEt—light petroleum, 1 : 10). IR, ν/cm–1: 2960, 2940, 2875,
1
1630, 1450, 1420, 1215, 1160, 765. H NMR, δ: 1.67 (m, 2 H);
1.74 (m, 2 H); 1.85 (m, 2 H); 2.48 (m, 2 H); 2.78 (m, 2 H). MS,
m/z (Irel (%)): 171 [M]+ (30), 143 [M – C2H4]+ (5), 136
•
[M – Cl]+ (27), 108 [M – Cl – C2H4]+ (27), 81 (41), 80 [M – Cl –
– C4H8]+ (36), 67 [C3HNO]+ (26), 55 (44), 41 (100). Found (%):
C, 55.75; H, 5.67; N, 8.22. C8H10ClNO. Calculated (%):
C, 55.98; H, 5.83; N, 8.16.
3ꢀChlorocyclooct[c]isoxazole (11d). Yield 10%, Rf 0.66
(AcOEt—light petroleum, 1 : 6). 1H NMR, δ: 1.65, 1.75, 1.85
(m, 8 H); 2.50 (m, 2 H); 2.80 (m, 2 H). MS, m/z (Irel (%)): 185
+
+
[M]+ (63), 150 [M – Cl ] (100), 122 [M – Cl – C2H4] (67),
•
95 (37), 80 [M – Cl – C5H10]
+ (34).
3,6,6ꢀTrichlorocyclopropa[5,6]cyclooct[1,2ꢀc]isoxazole (14).
Yield 75%, m.p. 75—77 °C. Rf 0.48 (AcOEt—light petroleum,
1 : 3). IR, ν/cm–1: 2960, 2940, 2875, 1630, 1450, 1420, 1215,
1160, 765. 1H NMR, δ: 1.53 (m, 1 H); 1.61 (m, 1 H); 1.76 (m, 2 H);
2.46 (m, 3 H); 2.74 (m, 2 H); 3.05 (ddd, 1 H, 3J = 3.6 Hz,
3J = 8.0 Hz, 2J = 11.7 Hz). Found (%): C, 45.10; H, 3.82;
N, 5.03. C10H10Cl3NO. Calculated (%): C, 45.11; H, 3.76; N, 5.26.
2ꢀDichloromethylidenecyclopentanone oxime (15). Yield 5%,
m.p. 135—136 °C. Rf 0.26 (AcOEt—light petroleum, 1 : 6). IR,
ν/cm–1: 3500—3200 (OH), 1590 (C=N). 1H NMR, δ: 1.85
Received May 21, 2010;
in revised form January 21, 2011