5
ꢀCyclopropylisoxazoleꢀbased synthesis
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 11, November, 2007 2187
Tetrabutylammonium salt of 3ꢀcyclopropylꢀ3ꢀoxopropionitrile
carried out as described above by passing 1.1 F of electricity per
mole of the starting compound (960 Q) until compound 1a was
fully consumed (TLC data). Then the solvent was evaporated
+
(
Bu N 3a). A solution of Bu NBr (3.22 g, 10 mmol) in anꢀ
4
4
+
hydrous MeOH (20 mL) was added to a solution of the Na salt
of cyano ketone 4a prepared as described previously. The mixꢀ
ture was stirred for 30 min at ~20 °C. The solvent was evapoꢀ
rated, dry МеCN (100 mL) was added, and the mixture was
1
from the catholyte under reduced pressure. The H NMR specꢀ
trum of the residue was fully identical to the spectrum of the
+
chemically prepared sample of the salt Bu N 3а (see above).
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+
refluxed for 40 min to complete extraction of the salt Bu N 3a.
Compound 4а was prepared by the standard workup of the
4
+
The NaBr precipitate was filtered off and МеCN was evaporated
on a rotary evaporator. Yield 3.46 g (99%). Found (%): C, 75.45;
precipitate of salt Bu N 3а (see above). This gave 0.77 g of
4
1
a yellowish oil, whose H NMR spectrum was identical to the
H, 12.01; N, 7.97. C22H42N O. Calculated (%): C, 75.43;
spectrum of the reference sample. The substance yield of comꢀ
pound 4а was 77% and the current yield was 72%.
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1
H, 12.00; N, 8.00. H NMR (CDCl ), δ: 3.25 (m, NCH ); 1.65,
3
2
1
.40 (both m, CH ); 1.00 (m, Me).
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Syntheses based on salts of cyano ketone 4а
Electrochemical experiments
+
3
ꢀAcetoxyꢀ3ꢀcyclopropylacrylonitrile (5). The salt Bu N 3а
4
Electrolysis was carried out in the galvanostatic mode
I = 0.1 A) in the cathodic compartment of a glass cell with a
ceramic diaphragm with a thermostatic jacket, a thermometer,
was electrogenerated (see above). After electrolysis, dry CHCl3
(30 mL) was added to the catholyte preꢀconcentrated to dryꢀ
ness, then a solution of AcCl (1.57 g, 20 mmol) in dry CHCl3
(20 mL) was slowly added with stirring over a period of 5 min;
the mixture spontaneously warmedꢀup to 45 °C. After 24 h, the
reaction mixture was washed with water (2×20 mL), the organic
solution was dried over Na SO (anhydr.), and the volatile comꢀ
(
and an N bubbling device. A B5ꢀ49 direct current source and a
2
coulometer (production of the N. D. Zelinsky Institute of Orꢀ
ganic Chemistry workshop) were incorporated in an electric
circuit. During electrolysis, the reaction mixture was stirred by a
2
4
2
magnetic stirrer. A stainlessꢀsteel plate (S = 47 cm ) was used as
ponents were distilled off to give 0.98 g (65%) of a yellow oil,
the cathode. A glass carbon plate served as the anode. Prior to
electrolysis, the steel cathode was kept for 3 min in dilute aqueꢀ
ous HCl (1 : 4) for activation, washed with distilled water, and
b.p. 120 °C (15 Torr). Found (%): C, 63.50; H, 5.90; N, 9.31.
1
C H NO . Calculated (%): C, 63.58; H, 5.96; N, 9.27. H NMR
8
9
2
(CDCl ), δ: 0.90, 1.25 (both m, 2 H each); 2.10 (s, 3 H); 2.25
3
dried. As supporting electrolytes, 0.1 М solutions of Bu NBr or
(m, 1 H); 5.40 (s, 1 H).
4
NaClO were used. The supporting salts (chemically pure) were
Enol acetate 5 was synthesized from the chemically generꢀ
4
+
dried prior to use by heating for 2 h on a water bath under
reduced pressure. The electrolysis was carried out until the startꢀ
ing isoxazole was completely consumed. The process was
monitored by TLC using Silufol UVꢀ254 plates (elution with
ated salt Bu N 3а (see above) using the same procedure. The
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+
reaction of Bu N 3а (3.5 g) gave 0.91 g (60%) of the target
4
product.
+
2ꢀCyanoꢀ1ꢀcyclopropylbutaneꢀ1,3ꢀdione (6). The salt Nа 3а
CCl —AcOEt, 10 : 4).
was prepared by electrosynthesis as described above. After elecꢀ
4
+
Electrosynthesis of Na 3а and its transformation into cyano
trolysis, dry CHCl (30 mL) was added to the catholyte preꢀ
3
ketone 4а. A 0.1 М solution of NaClO (100 mL) and isoxazole 1a
concentrated to dryness, then a solution of AcCl (1.57 g,
4
(
1 g, 9 mmol) were placed into the cathodic compartment of the
20 mmol) in dry CHCl (20 mL) was slowly added with stirring
3
cell and a 0.1 М solution of NaClO4 in МеCN (40 mL) was
placed into the anodic compartment. After deaeration of the
catholyte for 10 min, electrolysis at I = 0.1 A, T = 20 °C and
continuous purging with nitrogen was carried out. After 1.5 F of
electricity per mole of the starting compound (1300 Q) was
passed, the electrolysis was stopped because isoxazole 1a was
completely consumed (TLC data). The cathode was washed
with МеOH (2×10 mL) to remove the stuck salt, the washing
was combined with the catholyte, and the solvent was evapoꢀ
rated under reduced pressure until a dry residue formed. The
over a period of 5 min; the mixture warmedꢀup to 40 °C. After
24 h, the reaction mixture was washed from NaCl, the volatile
components were distilled off on a rotary evaporator under reꢀ
duced pressure. The residue was purified via the synthesis of
copper chelate. For this purpose, the residue was dissolved in
EtOH (10 mL) and this solution was added with vigorous stirꢀ
ring to a saturated solution of Cu(OAc) (30 mL). After stirring
2
for 4 h, the precipitate was filtered off and washed on the filter
with EtOH. Then the wet complex was decomposed by adding
concentrated HCl (10 mL) (to dissolve the precipitate) followed
by extraction with CH Cl (3×20 mL). The extract was dried
1
+
H NMR spectrum of salt Na 3а obtained in this way coincided
2
2
with the spectrum of chemically synthesized sample (see above).
The precipitate of salt Na 3а was acidified with a 0.1 М
aqueous HCl (50 mL) and extracted with ether (3×50 mL). The
over Na SO (anhydr.) and the solvent was evaporated under
2 4
+
reduced pressure. The yield of thus purified product 6 was 0.317 g
(21%), m.p. 56 °C. Found (%): C, 63.29; H, 6.05; N, 9.23.
1
ether extracts were dried over Na SO (anhydr.) and concenꢀ
C H NO . Calculated (%): C, 63.58; H, 5.96; N, 9.27. H NMR
2
4
8
9
2
trated in vacuo. The residual yellowish oil (0.71 g) was almost
pure cyano ketone 4а ( H NMR, cf. Ref. 1). The substance yield
(CDCl ), δ: 17.20 (s, 1 H, OH); 2.30 (s, 3 H, Ac); 2.20 (m,
1 H, cyclopropyl CH); 1.25, 1.10 (both m, 2 H each, cycloꢀ
3
1
of 3ꢀcyclopropylꢀ3ꢀoxopropionitrile (4а) was 71% and the curꢀ
propyl CH ).
2
rent yield was 48%.
Compound 6 was obtained from chemically prepared salt
Na 3а and purified as described above. Yield 22%.
+
+
Electrosynthesis of the salt Bu N 3а and its transformation
4
into cyano ketone 4а. A 0.1 М solution of Bu NBr (100 mL) and
isoxazole 1a (1 g, 9 mmol) were placed into the cathodic comꢀ
5ꢀAminoꢀ3ꢀcyclopropylisoxazole (7). The catholyte containꢀ
ing the salt Na 3a (10 mmol) was concentrated to dryness.
4
+
partment and a 0.1 М solution of Bu NBr in МеCN (40 mL)
A solution of hydroxylamine hydrochloride (0.7 g, 10 mmol)
4
was placed into the anodic compartment. The electrolysis was
in H O (20 mL) was added to the residue, and the mixture was
2