Synthesis of sulfonate derivatives of 4-heteryl-isoxazoles

Article abstract of DOI:10.1007/s11172-014-0404-2

Synthesis procedure of 3,5-dimethyl-4-heteryl-isoxazoles by reaction between heterocyclic aldehydes and nitroethane in the presence of base was developed. Sulfochlorination of the resulting compounds was studied.

Full text of DOI:10.1007/s11172-014-0404-2

Russian Chemical Bulletin, International Edition, Vol. 63, No. 1, pp. 118—122, January, 2014
118
Synthesis of sulfonate derivatives of 4ꢀheterylꢀisoxazoles*
L. A. Shumilova, M. K. Korsakov, M. V. Dorogov, and E. E. Shalygina
K. D. Ushinsky Yaroslavl State Pedagogical University,
108 ul. Respublikanskaya, 150000 Yaroslavl, Russian Federation.
Fax: (485 2) 73 1529. Еꢀmail: shumilova08@bk.ru
Synthesis procedure of 3,5ꢀdimethylꢀ4ꢀheterylꢀisoxazoles by reaction between heterocyclic
aldehydes and nitroethane in the presence of base was developed. Sulfochlorination of the
resulting compounds was studied.
Key words: isoxazole, cyclocondensation, sulfochlorination, electrophilic substitution.
Synthesis of 4ꢀheteryl substituted 3,5ꢀdimethylꢀisoxaꢀ
On the base of 3,5ꢀdimethylꢀ4ꢀheterylꢀisoxazoles 3
soles and their functionalization by electrophilic substituꢀ
tion reactions have not been investigated according to the
literature. One pot synthesis of 3,5ꢀdimethylꢀ4ꢀarylꢀisoxꢀ
azoles from corresponding aromatic aldehydes and nitroꢀ
ethane by refluxing in a waterꢀethanolic solution of alkali
is known.1 The need of complex chromatographic purifiꢀ
cation of target compounds from a great number of byꢀ
products is a major drawback of the procedure. The synꢀ
thesis of 3,5ꢀdimethylꢀ4ꢀarylꢀisoxazoles2 from aromatic
aldehydes and nitroethane in the presence of aluminum
oxide at 140 C under microwave irradiation has also been
reported. Higher yields of the products are achieved in this
work, but a more complicated procedure of the synthesis
is required. Absence of microwave irradiation under the
same conditions leads to very low yields (less than 3%)3 of
the products formed on the solid support. The use of other
bases for cyclocondensation — sodium carbonate and
Nꢀbutylamine,4 triethylamine,5 or pyrrolidine6 — also led
to low yield and low purity of target products. Sulfofuncꢀ
tionalization of 3,5ꢀdimethylꢀ4ꢀarylꢀisoxazoles proceeds
via sulfochlorination reactions,7,8 while investigations for
heterocyclic derivatives have not been done.
We have developed twoꢀstage scheme of 3,5ꢀdimethꢀ
ylꢀ4ꢀheterylꢀisoxazole synthesis from corresponding hetꢀ
erocyclic aldehydes 1 (Scheme 1). At the first stage, their
reaction with nitroethane in the presence of butylamine
acting as a base results in the formation of nitro adducts 2.
Subsequent cyclocondensation with the second molecule of
nitroethane has been carried out in an alkaline waterꢀethanꢀ
olic solution at ambient temperature during 21 days. The
temperature increase led to significant rise of the number of
byꢀproducts and to resinification of reaction mixture. As
a result, 3,5ꢀdimethylꢀ4ꢀheterylꢀisoxazoles 3 were obtained.
obtained, corresponding sulfonyl chlorides 4 were syntheꢀ
sized by their reaction with chlorosulfuric acid. Sulfoꢀ
chlorination was carried out with the excess of chloroꢀ
sulfuric acid in the presence of thionyl chloride at 60 C.
Structure and purity of synthesized compounds were
proved by the combination of elemental analysis, mass
spectrometry and NMR spectroscopy methods. Electroꢀ
philic attack at sulfochlorination of compounds 3a,b proꢀ
ceeds at position 5 of the thiophene or furan ring, and it is
confirmed by the existence of two doublet signals with
coupling constants of 3.7 Hz in 1H NMR spectra of comꢀ
pounds 4а,b.
1
As H NMR spectra of compounds 4c—g are diffiꢀ
cult to interpret, twoꢀdimensional homonuclear NOESY
1H NMR spectraof their sulfonamide derivatives 5a—e
were recorded in order to reliably confirm the structures.
Compounds 5a—e were synthesized by heating correꢀ
sponding sulfonyl chloride 4c—g with pyrrolidine in acetoꢀ
nitrile in the presence of pyridine. Couplings of nearly
1
located protons based on the interpretation of H NMR
NOESY spectra of compounds 5a,b, are presented below.
Coupling between methylene protons of the pyrroliꢀ
dine fragment and protons of methyl groups at position 5
of furan (or thiophene) is observed for compounds 5a and
5b, coupling of proton of furan (or thiophene) with the
protons of methyl group at position 3 of the isoxazole ring
and with methylene protons of pyrrolidine fragment is
also observed. This type of coupling confirms the presence
of aromatic proton at position 3 and sulfonyl group at
position 4 of heterocycle. Simultaneous coupling of one of
the furan or thiophene protons with methyl protons of the
isoxazole ring and with methylene protons of the pyrrolꢀ
idine fragment is observed for compounds 5c and 5d, reꢀ
spectively. This type of proton coupling proves the presꢀ
ence of sulfonyl group at position 5 of the heterocycle.
Simultaneous coupling of thiophene proton with the meꢀ
thyl protons at position 3 of thiophene and with methylꢀ
* On the basis of cluster of conferences on organic chemistry
"OrgChemꢀ2013" [OrgKhimꢀ2013] (June 17—21, 2013,
St.ꢀPetersburg, Repino).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0118—0122, January, 2014.
1066ꢀ5285/14/6301ꢀ0118 © 2014 Springer Science+Business Media, Inc.

Sulfonate derivatives of 4ꢀheterylꢀisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 1, January, 2014
119
Scheme 1
Het =
(a),
(b),
(c),
(d),
(e),
(f),
(g)
i. EtNO2, BuNH2, MeOH, 8 h, ; ii. EtNO2, NaOH, EtOH, 21 days.

120
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 1, January, 2014
Shumilova et al.
3ꢀ(2ꢀNitropropꢀ1ꢀenyl)thiophene (2f), 80% yield, lightꢀbrown
crystals, m.p. 68—70 C (methanol). Found (%): С, 49.65; Н,
4.17; N, 8.32; S, 18.99. С7Н7NO2S. Calculated (%): С, 49.69;
Н, 4.17; N, 8.28; S, 18.95. 1H NMR (DMSOꢀd6, , J/Hz): 2.44
(s, 3 Н, Me); 7.47 (d, 1 Н, С(5)Нthioph, J = 5.1); 7.74 (dd, 1 Н,
ene protons of pyrrolidine fragment is observed for sulꢀ
fonamide 5e, which confirms the existence of sulfonyl
group at position 5.
Experimental
С(4)Нthioph, J1 = 2.9, J2 = 5.1); 8.12 (m, 2 Н, С(2)Нthioph
,
СНСMe).
3ꢀMethylꢀ2ꢀ(2ꢀnitropropꢀ1ꢀenyl)thiophene (2g), 80% yield,
lightꢀbrown crystals, m.p. 75.5—77 C (methanol). Found (%):
С, 52.35; Н, 4.96; N, 7.68; S, 17.53. С8Н9NO2S. Calculated (%):
С, 52.44; Н, 4.95; N, 7.64; S, 17.50. 1H NMR (DMSOꢀd6, ,
J/Hz): 2.39 (s, 3 Н, Me); 2.48 (s, 3 Н, Me); 7.17, 7.96 (both d,
to 1 Н, СНthioph, J = 5.1); 8.29 (s, 1 Н, СНСMe).
Synthesis of 4ꢀheterylꢀisoxazoles 3 (general procedure).
Compound 2 (0.1 mol) was added to a mixture of nitroethane
(0.1 mol) and sodium hydroxide (0.25 mol) in 80 mL of waterꢀ
ethanol solution (30 : 70) while stirring without heating for
21 days. The reaction mixture was extracted with 100 mL of
ethyl acetate—petroleum ether mixture (50 : 50). The extract
was dried by sodium sulfate, flashꢀchromatographed on silica,
and the solvent was evaporated. Residual dark oil is crystallized
on friction.
3,5ꢀDimethylꢀ4ꢀ(furanꢀ2ꢀyl)isoxazole (3a), 84% yield, brown
crystals, m.p. 44—45 C (ethyl acetate). Found (%): С, 66.15;
Н, 5.57; N, 8.63. С9Н9NO2. Calculated (%): С, 66.25; Н, 5.56;
N, 8.58. 1H NMR (DMSOꢀd6, , J/Hz): 2.33 (s, 3 Н, Me); 2.54
(s, 3 Н, Me); 6.61 (m, 2 Н, 2 СНfur); 7.77 (m, 1 Н, СНfur). MS
(EI, 150 eV), m/z (Irel (%)): 163 [M]+ (28), 107 (15), 94 (10), 66
(41), 65 (8), 51 (26), 50 (11), 43 (100).
3,5ꢀDimethylꢀ4ꢀ(thiophenꢀ2ꢀyl)isoxazole (3b), 74% yield,
brown crystals, m.p. 54—55 C (ethyl acetate). Found (%):
С, 60.25; Н, 5.07; N, 7.85; S, 17.92. С9Н9NOS. Calculated (%):
С, 60.31; Н, 5.06; N, 7.81; S, 17.89. 1H NMR (DMSOꢀd6, ,
J/Hz): 2.30 (s, 3 Н, Me); 2.48 (s, 3 Н, Me); 7.19 (m, 2 Н,
2 СНfur); 7.64 (d, 1 Н, СНthioph, J = 4.6). MS (EI, 150 eV), m/z
(Irel (%)): 179 [M]+ (56), 136 (9), 122 (9), 111 (7), 110 (69),
109 (16), 96 (44), 95 (22), 69 (29), 66(14).
GCꢀMS analysis was carried out on an Applied Biosystems
instrument (Shimadzu 10ꢀAV LC, Gilsonꢀ215 automatic samꢀ
pling, API 150EX massꢀspectrometer, UV (215 and 254 nm) and
ELS detectors, LunaꢀC18 column, Phenomenex, 5 cm×2 mm).
1H NMR spectra of the samples in DMSOꢀd6 and CDCl3
solutions were recorded on a Bruker MSLꢀ300 spectrometer.
Twoꢀdimensional homonuclear NOESY 1H NMR spectra of
the samples in DMSOꢀd6 solutions were recorded on a Varian
XLꢀ400 instrument.
Elemental analyses were performed by the Laboratory of
organic microanalysis of N. D. Zelinsky Institute of Organic
Chemistry of Russian Academy of Sciences. Melting points were
obtained by using a Buchi Melting Point Mꢀ560 instrument.
Synthesis of compounds 2 (general procedure). A mixture of
appropriate aldehyde 1 (0.10 mol), nitroethane (0.10 mol), and
butylamine (1 mL) in 20 mL of methanol was refluxed for 8 h.
After that the mixture was cooled to –18 C. Large crystals of
precipitate were filtered off, washed with 30 mL of methanol,
and dried at room temperature.
2ꢀ(2ꢀNitropropꢀ1ꢀenyl)furan (2a), 76% yield, brown crysꢀ
tals, m.p. 99.5—100 C (methanol). Found (%): С, 54.85; Н, 4.61;
N, 9.19. С7Н7NO3. Calculated (%): С, 54.91; Н, 4.61; N, 9.15.
1H NMR (DMSOꢀd6, , J/Hz)**: 2.51 (s, 3 Н, Me); 6.77 (dd, 1 Н,
С(4)Нfur, J1 = 1.5, J2 = 3.3); 7.21 (d, 1 Н, С(3)Нfur, J = 3.3);
7.93 (s, 1 Н, СНСMe); 8.05 (d, 1 Н, С(5)Нfur, J = 1.5).
2ꢀ(2ꢀNitropropꢀ1ꢀenyl)thiophene (2b), 78% yield, yellow
crystals, m.p. 59—60 C (methanol). Found (%): С, 49.65;
Н, 4.17; N, 8.32; S, 18.99. С7Н7NO2S. Calculated (%): С, 49.69;
Н, 4.17; N, 8.28; S, 18.95. 1H NMR (DMSOꢀd6, , J/Hz)**:
2.48 (s, 3 Н, Me); 7.3 (dd, 1 Н, С(4)Нthioph, J1 = 3.7, J2 = 4.8);
3,5ꢀDimethylꢀ4ꢀ(5ꢀmethylfuranꢀ2ꢀyl)isoxazole (3c), 79%
yield, dark liquid, b.p. 198—200 C. Found (%): С, 67.65;
Н, 6.26; N, 7.94. С10Н11NO2. Calculated (%): С, 67.78; Н, 6.26;
N, 7.90. 1H NMR (DMSOꢀd6, , J/Hz): 2.31 (s, 6 Н, 2 Me); 2.52
7.77 (d, 1 Н, С(3)Нthioph, J = 3.7); 8.03 (d, 1 Н, С(5)Нthioph
J = 4.8); 8.40 (s, 1 Н, СНСMe).
2ꢀMethylꢀ5ꢀ(2ꢀnitropropꢀ1ꢀenyl)furan (2c), 82% yield, orꢀ
ange crystals, m.p. 77—78 C (methanol). Found (%): С, 59.55;
Н, 6.13; N, 7.77. С8Н9NO3. Calculated (%): С, 59.66; Н, 6.12;
N, 7.73. 1H NMR (DMSOꢀd6, , J/Hz): 2.39 (s, 3 Н, Me); 2.49
,
(s, 3 Н, Me); 6.20 (d, 1 Н, С(4)Нfur, J = 3.3); 6.47 (d, 1 Н, С(3)Нfur
,
J = 3.3). MS (EI, 150 eV), m/z (Irel (%)): 177 [M]+ (6), 125 (8),
108 (10), 107 (8), 93 (9), 79 (7), 65 (9), 53 (15), 51 (14), 43 (100).
3,5ꢀDimethylꢀ4ꢀ(5ꢀmethylthiophenꢀ2ꢀyl)isoxazole (3d), 74%
yield, brown crystals, m.p. 61—62 C (ethyl acetate). Found (%):
С, 62.05; Н, 5.74; N, 7.28; S, 16.62. С10Н11NOS. Calculated (%):
С, 62.15; Н, 5.74; N, 7.25; S, 16.59. 1H NMR (DMSOꢀd6, , J/Hz):
2.27 (s, 3 Н, Me); 2.46 (s, 3 Н, СН3); 2.50 (s, 3 Н, С(2)Нthioph);
6.86 (d, 1 Н, СНthioph, J = 2.6); 6.98 (d, 1 Н, СНthioph, J = 2.6).
MS (EI, 150 eV), m/z (Irel (%)): 193 [M]+ (39), 167 (8), 150 (6),
149 (32), 123 (16), 110 (13), 109 (11), 69 (24), 57 (34).
(s, 3 Н, Me); 6.42 (d, 1 Н, СНfur, J = 2.9); 7.13 (d, 1 Н, СНfur
J = 2.9); 7.86 (s, 1 Н, СНСMe).
,
2ꢀMethylꢀ5ꢀ(2ꢀnitropropꢀ1ꢀenyl)thiophene (2d), 76% yield,
yellow crystals, m.p. 98—100 C (methanol). Found (%): С, 52.35;
Н, 4.96; N, 7.68; S, 17.53. С8Н9NO2S. Calculated (%): С, 52.44;
Н, 4.95; N, 7.64; S, 17.50. 1H NMR (DMSOꢀd6, , J/Hz): 2.43
(s, 3 Н, Me); 2.54 (s, 3 Н, Me); 7.02 (d, 1 Н, СНthioph, J = 3.3);
7.60 (d, 1 Н, СНthioph, J = 3.3); 8.31 (s, 1 Н, СНСMe).
3ꢀ(2ꢀNitropropꢀ1ꢀenyl)furan (2e), 78% yield, brown crystals,
m.p. 56—57 C (methanol). Found (%): С, 54.85; Н, 4.61;
N, 9.19. С7Н7NO3. Calculated (%): С, 54.91; Н, 4.61; N, 9.15.
1H NMR (DMSOꢀd6, , J/Hz): 2.40 (s, 3 Н, Me); 7.21 (d, 1 Н,
С(5)Нfur, J = 5.1); 7.58 (dd, 1 Н, С(4)Нfur, J1 = 2.8, J2 = 5.1);
8.22 (d, 1 Н, С(2)Нfur, J = 2.8); 8.25 (s, 1 Н, СНСMe).
3,5ꢀDimethylꢀ4ꢀ(furanꢀ3ꢀyl)isoxazole (3e), 82% yield, brown
crystals, m.p. 95—97 C (ethyl acetate). Found (%): С, 66.15;
Н, 5.57; N, 8.63. С9Н9NO2. Calculated (%): С, 66.25; Н, 5.56;
N, 8.58. 1H NMR (DMSOꢀd6, , J/Hz): 2.26 (s, 3 Н, Me); 2.43
(s, 3 Н, Me); 6.74 (d, 1 Н, СНfur); 6.79 (s, 1 Н, СНfur); 7.91 (d, 1 Н,
СНfur). MS (EI, 150 eV), m/z (Irel (%)): 163 [M]+ (28), 107 (5),
94 (10), 79 (8), 66 (41), 51 (26), 50 (11), 43 (100).
* Hfur are furan atoms.
** Hthioph are thiophene atoms.
3,5ꢀDimethylꢀ4ꢀ(thiophenꢀ3ꢀyl)isoxazole (3f), 81% yield,
brown crystals, m.p. 70—72 C (ethyl acetate). Found (%):

Sulfonate derivatives of 4ꢀheterylꢀisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 1, January, 2014
121
С, 60.25; Н, 5.07; N, 7.85; S, 17.92. С9Н9NOS. Calculated (%):
С, 60.31; Н, 5.06; N, 7.81; S, 17.89. 1H NMR (DMSOꢀd6, ,
Found (%): С, 41.19; Н, 3.08; N, 5.38; S, 12.28. С9Н8ClNO4S.
Calculated (%): С, 41.31; Н, 3.08; N, 5.35; S, 12.25. H NMR
1
J/Hz): 2.26 (s, 3 Н, Me); 2.43 (s, 3 Н, Me); 7.27 (d, 1 Н, СНthioph
,
(CDCl3, , J/Hz): 2.22 (s, 3 Н, СН3); 2.42 (s, 3 Н, СН3); 7.04
(s, 1 Н, СНfur); 7.35 (s, 1 Н, СНfur). MS (EI, 150 eV), m/z
(Irel (%)): 261 [M]+ (12), 162 (7), 157 (6), 43 (100).
J = 4.4); 7.61 (s, 1 Н, СНthioph); 7.69 (d, 1 Н, СНthioph, J = 4.4).
MS (EI, 150 eV), m/z (Irel (%)): 179 [M]+ (16), 110 (13), 109 (5),
95 (7), 77 (100), 68 (10), 51 (84), 39 (29).
4ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)thiopheneꢀ2ꢀsulfonyl chloride
(4f), 80% yield, brown crystals, m.p. 103—105 C (petroleum
ether). Found (%): С, 38.85; Н, 2.91; N, 5.07; S, 23.13.
С9Н8ClNO3S2. Calculated (%): С, 38.31; Н, 5.06; N, 7.81;
3,5ꢀDimethylꢀ4ꢀ(3ꢀmethylthiophenꢀ2ꢀyl)isoxazole (3g), 80%
yield, brown crystals, m.p. 90—92 C (ethyl acetate). Found (%):
С, 62.05; Н, 5.74; N, 7.28; S, 16.62. С10Н11NOS. Calculated (%):
С, 62.15; Н, 5.74; N, 7.25; S, 16.59. 1H NMR (DMSOꢀd6, ,
J/Hz): 2.04 (s, 3 Н, СН3); 2.10 (s, 3 Н, СН3); 2.29 (s, 3 Н, СН3);
7.04 (d, 1 Н, СНthioph, J = 5.3); 7.58 (d, 1 Н, СНthioph, J = 5.3).
MS (EI, 150 eV), m/z (Irel (%)): 193 [M]+ (14), 149 (11), 124 (17),
123 (7), 110 (12), 109 (9), 69 (12), 57 (21).
Synthesis of sulfonyl chlorides 4 (general procedure). Approꢀ
priate 4ꢀheterylꢀisoxazole 3 (0.01 mol) was added portionwise to
a cooled (by ice bath) mixture of chlorosulfuric acid (0.10 mol)
and thionyl chloride (0.01 mol) with intensive stirring. The mixꢀ
ture was kept cooled till the complete dissolution of precipitate,
then it was heated at 60 C during 1 h. The reaction mixture was
poured into a mixture of ice and chloroform (50 mL). The orꢀ
ganic layer was separated, washed with 50 mL of 5% sodium
bicarbonate solution, and dried by sodium sulfate. The solution
was flashꢀchromatographed on silica, the solvent was evaporatꢀ
ed. Petroleum ether (50 mL) was added to the residue, and the
crystals of sulfonyl chloride 4 were filtered.
1
S, 17.89. H NMR (CDCl3, , J/Hz): 2.24 (s, 3 Н, СН3); 2.41
(s, 3 Н, СН3); 7.19 (s, 1 Н, СНthioph); 7.47 (s, 1 Н, СНthioph).
MS (EI, 150 eV), m/z (Irel (%)): 277 [M]+ (4), 178 (5), 173 (5),
48 (8), 45 (12), 43 (100), 30 (6).
5ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)ꢀ4ꢀmethylthiopheneꢀ2ꢀsulfonyl
chloride (4g), 82% yield, brown crystals, m.p. 102—104 C
(petroleum ether). Found (%): С, 41.15; Н, 3.46; N, 4.82;
S, 22.02. С10Н10ClNO3S2. Calculated (%): С, 41.17; Н, 3.45;
N, 4.80; S, 21.98. 1H NMR (CDCl3, , J/Hz): 2.03 (s, 3 Н,
СН3); 2.10 (s, 3 Н, СН3); 2.26 (s, 3 Н, СН3); 7.64 (s, 1 Н,
СНthioph). MS (EI, 150 eV), m/z (Irel (%)): 291 [M]+ (16), 256 (7),
166 (10), 152 (5), 151 (53), 134 (22), 123 (20), 109 (22), 93 (17),
69 (20).
Synthesis of sulfonamides 5a—e (general procedure). Pyrroliꢀ
dine (0.001 mol) was added to a mixture of sulfonyl chloride 4
(0.001 mol) and pyridine (0.002 mol) in acetonitrile (5 mL). The
reaction mixture was stirred at 60 C for 0.5 h. Water (5 mL) was
added to the mixture, the resulting precipitate was filtered off
and recrystallized from isopropyl alcohol.
3,5ꢀDimethylꢀ4ꢀ[5ꢀmethylꢀ4ꢀ(pyrrolidinꢀ1ꢀsulfonyl)furanꢀ2ꢀ
yl]isoxazole (5a), 71% yield, white crystals, m.p. 145—147 C
(isopropyl alcohol). Found (%): С, 54.09; Н, 5.85; N, 9.07;
S, 10.35. С14Н18N2O4S. Calculated (%): С, 54.18; Н, 5.85;
N, 9.03; S, 10.33. 1H NMR (DMSOꢀd6, , J/Hz)*: 1.74 (m, 4 Н,
2 СН2pyr); 2.34 (s, 3 Н, Ме); 2.50 (s, 3 Н, Ме); 2.57 (s, 3 Н,
Ме); 3.20 (m, 4 Н, 2 СН2Npyr); 6.82 (d, 1 Н, С(3)Нfur). MS (EI,
150 eV), m/z (Irel (%)): 310 [M]+ (10), 177 (9), 176 (10), 175 (9),
148 (9), 124 (24), 106 (9), 70 (100), 42 (50).
3,5ꢀDimethylꢀ4ꢀ[5ꢀmethylꢀ4ꢀ(pyrrolidineꢀ1ꢀsulfonyl)thioꢀ
phenꢀ2ꢀyl]isoxazole (5b), 77% yield, lightꢀbrown crystals, m.p.
115—117 C (isopropyl alcohol). Found (%): С, 51.48; Н, 5.56;
N, 8.62; S, 19.68. С14Н18N2O3S2. Calculated (%): С, 51.51;
Н, 5.56; N, 8.58; S, 19.64. 1H NMR (DMSOꢀd6, , J/Hz): 1.75
(m, 4 Н, 2 СН2pyr); 2.29 (s, 3 Н, Ме); 2.48 (s, 3 Н, Ме); 2.70
(s, 3 Н, Ме); 3.22 (m, 4 Н, 2 СН2Npyr); 7.25 (s, 1 Н, С(3)Нthioph).
MS (EI, 150 eV), m/z (Irel (%)): 326 [M]+ (53), 191 (18), 148 (9),
70 (40), 69 (11), 65 (6), 59 (16), 43 (100).
5ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)furanꢀ2ꢀsulfonyl chloride (4a),
78% yield, brown crystals, m.p. 61—63 C (petroleum ether).
Found (%): С, 41.19; Н, 3.08; N, 5.38; S, 12.28. С9Н8ClNO4S.
1
Calculated (%): С, 41.31; Н, 3.08; N, 5.35; S, 12.25. H NMR
(CDCl3, , J/Hz): 2.44 (s, 3 Н, СН3); 2.64 (s, 3 Н, СН3); 6.53
(d, 1 Н, СНfur, J = 3.7); 7.36 (d, 1 Н, СНfur, J = 3.7). MS (EI,
150 eV), m/z (Irel (%)): 261 [M]+ (16), 178 (9), 136 (15), 134 (27),
121 (62), 90 (22), 79 (40), 76 (18), 65 (15).
5ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)thiopheneꢀ2ꢀsulfonyl chloride
(4b), 82% yield, brown crystals, m.p. 82—84 C (petroleum
ether). Found (%): С, 38.85; Н, 2.91; N, 5.07; S, 23.13.
С9Н8ClNO3S2. Calculated (%): С, 38.31; Н, 5.06; N, 7.81;
1
S, 17.89. H NMR (CDCl3, , J/Hz): 2.39 (s, 3 Н, СН3); 2.56
(s, 3 Н, СН3); 7.04 (d, 1 Н, СНthioph, J = 3.7); 7.87 (d, 1 Н,
СНthioph, J = 3.7). MS (EI, 150 eV), m/z (Irel (%)): 277 [M]+ (7),
194 (5), 152 (8), 137 (23), 120 (17), 109 (11), 95 (12), 93 (12),
69 (13).
5ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)ꢀ2ꢀmethylfuranꢀ3ꢀsulfonyl chlorꢀ
ide (4c), 80% yield, white crystals, m.p. 115—117 C (petroleum
ether). Found (%): С, 43.55; Н, 3.66; N, 5.11; S, 11.65.
С10Н10ClNO4S. Calculated (%): С, 43.56; Н, 3.66; N, 5.08;
3,5ꢀDimethylꢀ4ꢀ[5ꢀ(pyrrolidineꢀ1ꢀsulfonyl)thiophenꢀ3ꢀyl]ꢀ
isoxazole (5c), 79% yield, lightꢀbrown crystals, m.p. 90—92 C
(isopropyl alcohol). Found (%): С, 49.88; Н, 5.17; N, 9.01; S, 20.57.
С13Н16N2O3S2. Calculated (%): С, 49.98; Н, 5.16; N, 8.97;
S, 20.52. 1H NMR (DMSOꢀd6, , J/Hz): 1.70 (m, 4 Н, 2 СН2pyr);
2.28 (s, 3 Н, Ме); 2.45 (s, 3 Н, Ме); 3.23 (m, 4 Н, 2 СН2Npyr);
1
S, 11.63. H NMR (CDCl3, , J/Hz): 2.39 (s, 3 Н, СН3); 2.56
(s, 3 Н, СН3); 2.69 (s, 3 Н, СН3); 6.63 (s, 1 Н, СНfur). MS (EI,
150 eV), m/z (Irel (%)): 275 [M]+ (32), 240 (16), 192 (11), 148 (13),
124 (20), 123 (15), 106 (15), 90 (29), 43 (100).
5ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)ꢀ2ꢀmethylthiopheneꢀ3ꢀsulfonyl
chloride (4d), 76% yield, darkꢀbrown crystals, m.p. 78—80 C
(petroleum ether). Found (%): С, 41.15; Н, 3.46; N, 4.82; S, 22.02.
С10Н10ClNO3S2. Calculated (%): С, 41.17; Н, 3.45; N, 4.80;
7.82 (d, 1 Н, С(4)Нthioph, J = 1.1); 8.06 (d, 1 Н, С(2)Нthioph
,
J = 1.1). MS (EI, 150 eV), m/z (Irel (%)): 312 [M]+ (14),
179 (14), 178 (12), 137 (10), 110 (11), 109 (11), 95 (11), 70 (15),
69 (10), 43 (96).
1
S, 21.98. H NMR (CDCl3, , J/Hz): 2.26 (s, 3 Н, СН3); 2.42
(s, 3 Н, СН3); 2.75 (s, 3 Н, СН3); 7.18 (s, 1 Н, СНthioph). MS (EI,
150 eV), m/z (Irel (%)): 291 [M]+ (6), 256 (3), 148 (6), 123 (7),
69 (9), 63 (7), 59 (14), 43 (100).
3,5ꢀDimethylꢀ4ꢀ[5ꢀ(pyrrolidineꢀ1ꢀsulfonyl)furanꢀ3ꢀyl]isoxꢀ
azole (5d), 73% yield, white crystals, m.p. 104—106 C (isoproꢀ
pyl alcohol). Found (%): С, 52.63; Н, 5.45; N, 9.50; S, 10.84.
4ꢀ(3,5ꢀDimethylisoxazolꢀ4ꢀyl)furanꢀ2ꢀsulfonyl chloride (4e),
76% yield, brown crystals, m.p. 62—65 C (petroleum ether).
* Hpyr are pyrrolidine atoms.

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Shumilova et al.
С13Н16N2O4S. Calculated (%): С, 52.69; Н, 5.44; N, 9.45;
S, 10.82. 1H NMR (DMSOꢀd6, , J/Hz): 1.62 (m, 4 Н, 2 СН2pyr);
2.30 (s, 3 Н, Ме); 2.51 (s, 3 Н, Ме); 3.22 (m, 4 Н, 2 СН2Npyr);
7.68 (s, 1 Н, С(4)Нfur); 8.20 (s, 1 Н, С(2)Нfur). MS (EI, 150 eV),
m/z (Irel (%)): 296 [M]+ (17), 163 (15), 121 (12), 95 (7), 69 (12),
43 (100).
3,5ꢀDimethylꢀ4ꢀ[3ꢀmethylꢀ5ꢀ(pyrrolidineꢀ1ꢀsulfonyl)thioꢀ
phenꢀ2ꢀyl]isoxazole (5e), 73% yield, lightꢀbrown crystals, m.p.
116—118 C (isopropyl alcohol). Found (%): С, 51.48; Н, 5.56;
N, 8.62; S, 19.68. С14Н18N2O3S2. Calculated (%): С, 51.51;
Н, 5.56; N, 8.58; S, 19.64. 1H NMR (DMSOꢀd6, , J/Hz): 1.72
(m, 4 Н, 2 СН2pyr); 2.08 (s, 3 Н, Ме); 2.13 (s, 3 Н, Ме); 2.33
(s, 3 Н, Ме); 3.21 (m, 4 Н, 2 СН2Npyr); 7.63 (s, 1 Н, С(4)Нthioph).
MS (EI, 150 eV), m/z (Irel (%)): 326 [M]+ (21), 193 (29), 166 (7),
151 (43), 134 (11), 124 (17), 109 (16), 70 (22), 69 (11).
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References
1. W. M. BestW.M. Best, E. L. GhisalbertiE.L. Ghisalberti,
Received October 10, 2013;
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in revised form December 9, 2013