Dioximes of 1,3-diketones in the trofimov reaction: New 3-substituted pyrroles

Article abstract of DOI:10.1007/s10593-005-0212-6

Dioximes of 1,3-diketones enter into the Trofimov reaction forming pyrroles containing an acyl or an O-vinyloxime substituent in position 3 of the pyrrole. In the case of sterically hindered dioximes the main reaction products are isoxazoles. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-005-0212-6

Chemistry of Heterocyclic Compounds, Vol. 41, No. 6, 2005
DIOXIMES OF 1,3-DIKETONES
IN THE TROFIMOV REACTION:
NEW 3-SUBSTITUTED PYRROLES
A. B. Zaitsev, E. Yu. Schmidt, A. M. Mikhaleva, A. V. Afonin, and I. A.Ushakov
Dioximes of 1,3-diketones enter into the Trofimov reaction forming pyrroles containing an acyl or an
O-vinyloxime substituent in position 3 of the pyrrole. In the case of sterically hindered dioximes the main
reaction products are isoxazoles.
Keywords: acetylene, 3-acylpyrroles, O-vinyloximes, 1-vinylpyrroles, dioximes of 1,3-diketones,
isoxazoles.
Heterocyclic compounds containing a 3-acylpyrrole fragment are of interest for making new
pharmacological preparations. For example, the cannabinoid activity of 1-alkyl-3-(naphthoyl)pyrroles [1] and
1-alkyl-3-(naphthoyl)indoles [2] is known, as is the antibiotic activity of verrucarin E, 3-acetyl-4-
hydroxymethylpyrrole, isolated from Myrothecium verrucaria [3]. 3-Acylpyrroles and other 3-substituted
pyrroles obtained from them are precursors of liquid crystal materials [4] and polypyrroles [5], possessing high
electrical conductivity in comparison with their 1-substituted analogs [6]. Such conjugated polymers may be
used for example to construct gas sensors [7], and also sensors capable of distinguishing DNA molecules [8].
The acylation reaction used in the majority of cases for the synthesis of 3-acylpyrroles has low
efficiency since electrophilic attack occurs predominantly at position 2 of the pyrrole ring. To direct substitution
to position 3 it is necessary to introduce readily removable blocking groups into position 2 (a thiocarboxylate
group [9]) or position 1 (triisopropylsilyl [10, 11], 1-phenylsulfonyl or 1-tosylsulfonyl [7, 12, 13]).
In the present work we have studied the possibility of synthesizing new 3-functionalized pyrroles with
the aid of the Trofimov reaction [14-19] by the interaction of dioximes of acetylacetone (1a), benzoylacetone
(1b), 5-ethylnonane-4,6-dione (1c), and 5,5-dimethylcyclohexane-1,3-dione (dimedone) (1d) with acetylene in
the presence of KOH in DMSO.
The selectivity of the interaction of dioxime 1a with acetylene depends strongly on the reaction
temperature. At 100°C (1 h) the O-vinyloxime pyrrole derivative 2a is formed exclusively (11% yield), and at
120°C (1 h) the main product is the 2,3'-bipyrrole 3 (7% yield).
Attention is attracted by the unusually high stability of the O-vinyloxime group of compound 2a under
the reaction conditions. The formation of a second pyrrole ring with its participation occurs only on increasing
the temperature to 120°C. It is known that for O-vinyloximes of 3-acylindoles pyrrolization in the system
KOH–DMSO is also hindered and at 100-105°C occurs completely only after 8-10 h [20]. The reduced reactivity
of the O-vinyloxime function at position 3 of the pyrrole ring in O-vinyloximes of 3-acylindoles
__________________________________________________________________________________________
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
Irkutsk 664033; e-mail: mikh@irioch.irk.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6,
pp. 839-847. June, 2005. Original article submitted May 12, 2003; revision submitted August 3, 2004.
722
0009-3122/05/4106-0722©2005 Springer Science+Business Media, Inc.

HX
α
HA
α
β
O
HX
HA
β
HB
5
N
N
Me
Me
120 o C
4
C2H2,
HB
100 oC
3'
NOH
NOH
C2H2,
4'
Me
2
3
2'
KOH/DMSO
KOH/DMSO
5'
Me
α'
HX'
Me
HX'
N
N
α'
HB'
HB'
1a
β'
β'
HA'
HA'
2a
3
enabled the isolation for the first time of a mixture of the corresponding O-vinyloximes containing an
α-methylene group [20], which was not possible up to the present time on vinylation of alkyl-, aryl-, and
2-hetaryl ketoximes [19, 21].
O
O
HN
NH
2a
Me
Me
H
N
N
4
OH
N
N
N
C2H2
3
KOH/DMSO
Me
Me
Me
N
N
N
Probably the hindering of the pyrrolization process of compound 2a is the result of the increased
electron density at position 3 of the pyrrole ring compared with position 2. The electron-donating effect of the
heterocycle on the O-vinyloxime group must lead to a reduction of the CH-acidity of the neighboring methyl
group, which is unfavorable for tautomeric conversion of compound 2a into the enehydroxylamine 4, [3,3]
sigmatropic rearrangement of which leads to bipyrrole 3.
It is also possible that hindrance of the pyrrolization process is a consequence of steric obstacles linked
with the presence of the heterocycle and the methyl group, which leads to disturbance of the coplanarity of the
double bonds in the O-vinyloxime substituent, necessary for a facile [3,3] sigmatropic rearrangement.
Lower reaction selectivity is observed for dioxime 1b. At 100°C a mixture of pyrroles 2b (4% yield), 5
1
(13% yield), and isoxazoles 6a,b (18% yield) is formed already after 5 min. According to data of H NMR
spectra the ratio 2b:5:6a:6b ≈ 1:3:2:2.
This mixture indicates that on interacting compound 1b with acetylene two competing reactions take
place. These are pyrrolization leading to oxime 2b and its deoximation product 5, and also intramolecular
nucleophilic addition of one oxime group to the other at the C=N bond with the formation of compounds 6a,b.
723

O
N
O
Me
Ph
Ph
Me
NOH
NOH
C2H2
Ph
Me
Ph
Me
+
+
+
KOH/DMSO
N
N
Me
Ph
N
N
O
O
1b
2b
6b
6a
5
An interesting fact in the present case is the regiospecific pyrrolization of dioxime 1b with the
participation of the oxime function of the acetyl fragment. This is probably caused by the higher nucleophilicity
and lower steric hindrance of the acetyl oxime group enabling its addition to acetylene. In view of the relative
ease of E,Z-isomerization of oxime functions under the reaction conditions [19], it may be suggested that the
marked regiospecificity is not linked with the configuration of the oxime functions of dioxime 1b, which is a
mixture of E,Z- and E,E-isomers (configurations of the PhC=N and MeC=N bonds respectively) at a ratio of 1:1
(1H NMR).
OH
N Me
OH
N
Me
Ph
Ph
N
N
OH
OH
E,Z-1b
E,E-1b
The ease of deoximation of compound 2b leading to pyrrole 5 is probably linked to the acceptor
influence of the phenyl substituent increasing the tendency of the neighboring O-vinyloxime group to
nucleophilic attack by hydroxide ion at the carbon atom.
Regiospecific pyrrolization with the participation of the more acidic methylene group in dioximes 1a,b
is one further indirect confirmation of the mechanism of the Trofimov reaction, including a [3,3] sigmatropic
rearrangement of the enehydroxylamines formed as a result of a prototropic tautomerization of O-vinyloximes
[19]. The latter must proceed readily on increasing the acidity of the methylene (methyl) group bound directly to
the O-vinyloxime function.
On the basis of the results obtained it is also possible to explain the more ready pyrrolization of
O-vinyloximes containing an α-methylene group. The enehydroxylamines formed in this case with a
disubstituted ethylene fragment are thermodynamically more stable and consequently their formation must
proceed more readily.
On introducing dioxime 1c into the Trofimov reaction only 4-ethyl-3,5-di(n-propyl)isoxazole 7
(21% yield) was isolated from the reaction mixture by column chromatography. This is formed by
intramolecular cyclization of the initial dioxime.
O
NOH
NOH NOH
H2O
2
8
9
1
7
3
5
Me
Me
Me
Me
6
4
KOH/DMSO
3'
Me
2'
Me
1c
Pr
Et
KOH/DMSO
N
Pr
O
7
724

It is possible that the steric effect of the propyl sidegroups hinders addition of the oxime functions to
acetylene.
It was shown that the formation of isoxazole 7 occurs under the action of water present in the
KOH–DMSO system. However at a concentration of water commensurate with the concentration of dioxime 1c,
only traces of product 7 are formed and practically all the initial dioxime remains unreacted. Probably a
preliminary deoximation (hydrolysis) of one of the oxime groups is necessary for cyclization, and the second
adds relatively readily to the electron-deficient carbonyl group formed.
The interaction of dimedone dioxime 1d with acetylene under Trofimov reaction conditions also did not
lead to the formation of pyrroles or O-vinyloximes. The reaction mixture was strongly resinified.
N
OH
6
5
1
C2H2
Me
Me
Resinous products
2
KOH/DMSO
4
3
N
OH
1d
Probably the conformation of compound 1d hinders its conversion into a pyrrole under the action of
acetylene and the formation of resinous compounds is the result of the condensation of products of deoximation
and breakdown of the cyclohexane ring under the action of the KOH–DMSO system. It is also possible that this
behavior of dioxime 1d is linked with its Z,Z-configuration, leading to a steric interaction of the oxime functions,
thus reducing their reactivity.
COSY and NOESY methods of homonuclear 2D spectroscopy and HSQC and HMBC methods of
heteronuclear 2D spectroscopy were used for the assignment of signals in the NMR spectra of the compounds
obtained. The paramagnetic broadening agent Gd(fod)3 was used for assigning the signals of isomers 6a,b.
Evidence of the existence of 5,5-dimethylcyclohexane-1,3-dione dioxime 1d as the Z,Z-isomer is the
displacement in the 13C NMR spectrum of the signal for atom C(2) by 34.2 ppm towards high field compared with
the initial ketone (57.35 ppm). The syn effect observed here is two times greater compared with the known value
for cyclohexanone oxime (-15.8 ppm [22]).
The chemical shift of the C(Ph)-i atom in oxime 2b (136.45 ppm) indicates the Z-configuration of its
O-vinyloxime group [23]. The low-field displacement of the C(3) atom signal in compound 2a (117.96 ppm)
relative to the C(3) signal of compound 2b (113.99 ppm) indicates the E-configuration of the considered group in
oxime 2a [24]. On the basis of the chemical shift of the methyl group carbon atoms in dioxime 1a (13.08 ppm) it
may be concluded that it exists as the E,E-isomer [24].
As a result of the investigations carried out the possibility has been shown of synthesizing by the
Trofimov reaction 2,3'-bipyrroles, 3-acylpyrroles, and their O-vinyloxime derivatives, unavailable in practice. It
has been established that the determining influence on the direction of the reaction proves to be the character of
the substituent in the 1,3-dioxime. The presence of bulky substituents or a six-membered ring makes side
reactions completely dominant.
In spite of the relatively low yields the compounds obtained or their analogs may after optimizing the
synthetic conditions become a basis for building new pharmacological preparations and contemporary high-
technology materials.
EXPERIMENTAL
The 1H NMR (400 MHz) and 13C (101 MHz) spectra were recorded on a Bruker 400DPX spectrometer,
1
internal standard was HMDS (δ 0.055 ppm for H and 2.00 ppm for 13C). The IR spectra were obtained on a
Bruker ISF 25 instrument. A Finnigan MAT 8200 spectrometer was used to record the mass spectra.
725

Acetylacetone Dioxime (1a). Acetylacetone (16.00 g, 159.8 mmol) was added to a mixture of
hydroxylamine hydrochloride (27.76 g, 399.6 mmol) and sodium acetate (32.78 g, 399.6 mmol) in methanol
(100 ml). The mixture obtained was stirred for 5 h then left for 16 h at room temperature. The precipitated solid
NaCl was filtered off, and washed with methanol. The total methanol solution was evaporated almost to dryness
in vacuum on a water bath (<50°C). Cold water (100 ml) was added to the residue, the mixture was thoroughly
stirred, the precipitated crystals were filtered off, washed with cold water (4 × 20 ml), and dried in the air.
Dioxime 1a (11.37 g, 54.7%) was obtained as white needle-like crystals; mp 128-134°C (mp 149-150°C [25-27],
105°C [28]). IR spectrum (KBr), ν, cm-1:3176 (OH), 3100 (CH), 2882 (CH), 1666 (C=N), 989 (N–O). 1H NMR
spectrum (DMSO-d6), δ, ppm: 10.49 (2H, s, 2NOH); 2.93 (2H, s, CH2); 1.69 (6H, s, 2CH3). 13C NMR spectrum
(DMSO-d6), δ, ppm: 152.29 (C=NOH); 41.65 (CH2); 13.08 (CH3). Found, %: C 46.60; H 7.95; N 21.53.
C5H10N2O2. Calculated, %: C 46.14; H 7.74; N 21.52.
Benzoylacetone Dioxime (1b). Sodium acetate (8.10 g, 98.7 mmol) and hydroxylamine hydrochloride
(6.86 g, 98.7 mmol) in methanol (30 ml) were stirred for 10 min. Benzoylacetone (4.00 g, 24.7 mmol) was added
to the obtained mixture, the reaction mixture was stirred for 4 days at room temperature, and then poured into
cold water (100 ml). After 3 h the precipitated solid was filtered off, washed with cold water, dried in vacuum,
and a mixture (1:1) of the E,E- and E,Z-isomers of dioxime 1b (3.08 g, 65%) was obtained as a white powder;
mp 84-86°C. IR spectrum (KBr), ν, cm-1: 3247 (OH), 3206 (CH), 3079 (CH), 2894 (CH), 1597 (C=N), 1569
(Ph), 1498 (Ph), 930 (N–O). 1H NMR spectrum (DMSO-d6), δ, ppm, mixture of isomers of 1b: E,E-1b 11.42 and
10.44 (2H, two br s, NOH); 7.76 (2H, m, HPh-o); 7.30 (3H, m, HPh-m, HPh-p); 3.41 (2H, s, CH2); 1.69 (3H, s,
CH3); E,Z-1b 11.49 and 10.65 (2H, two br s, NOH); 7.76 (2H, m, HPh-o); 7.30 (3H, m, HPh-m, HPh-p); 3.61 (2H,
s, CH2); 1.58 (3H, s, CH3). 13C NMR spectrum (DMSO-d6), δ, ppm, mixture of isomers: E,E-1b 153.66 and
153.30 (MeC=N, PhC=N); 137.39 (CPh-i); 129.63 (CPh-m); 127.25 (CPh-o); 126.87 (CPh-p); 32.60 (CH2); 14.80
(CH3); E,Z-1b 153.89 and 152.19 (MeC=N, PhC=N); 137.25 (CPh-i); 130.26 (CPh-p); 129.99 (CPh-o); 129.85
(CPh-m); 26.36 (CH2); 19.95 (CH3). Found, %: C 61.97; H 6.31; N 14.56. C10H12N2O2. Calculated, %: C 62.49; H
6.29; N 14.57.
5-Ethylnonane-4,6-dione Dioxime (1c). Sodium acetate (8.86 g, 108.0 mmol) and hydroxylamine
hydrochloride (7.51 g, 108.1 mmol) in methanol (15 ml) were stirred for 10 min. 5-Ethylnonane-4,6-dione
(5.00 g, 27.1 mmol) was added to the obtained mixture, the reaction mixture was stirred for 8 days at room
temperature, and then poured into cold water (50 ml). The precipitated solid was filtered off, washed with cold
water, dried in vacuum, and dioxime 1c (3.34 g, 58% yield) was obtained as a white powder (3:2 mixture of E,E-
and E,Z-isomers); mp 80-84°C. IR spectrum (KBr), ν, cm-1: 3260 (OH), 3152 (CH), 2967 (CH), 2936 (CH),
1
2875 (CH), 1652 (C=N), 966 (N-O). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz), mixture of isomers of
3
dioxime 1c: E,E-1c 10.49 (2H, s, 2NOH); 2.91 (1H, t, J5,1' = 7.5, H-5); 2.31-1.32 (10H, m, CH2); 0.85 (6H, t,
3J1,2 = 3J8,9 =7.4, C(1)H3 and C(9)H3); 0.81 (3H, t, 3J1',2' = 7.3, C(2')H3); E,Z-1c 10.60 (1H, s, Z-NOH); 10.49 (1H, s,
3
3
3
3
E-NOH); 4.12 (1H, dd, J5,1'a = 6.8, J5,1'b = 8.3, H-5); 2.31-1.32 (10H, m, CH2); 0.85 (6H, t, J1,2 = J8,9 =7.4,
C(1)H3 and C(9)H3); 0.81 (3H, t, 3J1',2' = 7.3, C(2')H3). 13C NMR spectrum (DMSO-d6), δ, ppm, mixture of isomers:
E,E-1c 157.70 (C(4), C(6)); 51.46 (C(5); 28.37 (C(3), C(7)); 21.67 (C(1')); 18.79 (C(2), C(8)); 14.51 (C(1), C(9); 12.21
(C(2')); E,Z-1c 157.00 (C(4)-E); 156.58 (C(6)-Z); 42.83 (C(5)); 31.42 (C(3)); 29.68 (C(7)); 21.10 (C(1')); 19.18 (C(2));
18.60 (C(8)); 14.25 (C(1)); 14.02 (C(9)); 12.10 (C(2')). Found, %: C 61.40; H 10. 44; N 13.01. C11H22N2O2.
Calculated, %: C 61.65; H 10.35; N 13.07.
5,5-Dimethylcyclohexane-1,3-dione Dioxime (1d). Finely powdered NaOH (3.57 g, 89.2 mmol) was
added in portions to a mixture of 5,5-dimethylcyclohexane-1,3-dione (5.00 g, 35.7 mmol) and hydroxylamine
hydrochloride (6.20 g, 89.2 mmol), ethanol (20 ml), and water (2 ml). The mixture was stirred at room
temperature for 1 h, and then poured into cold water (100 ml). The precipitated solid was filtered off, washed
with cold water, and dried in vacuum. Dioxime 1d (2.35 g, 39%) was obtained as a white powder;
mp 155-158°C. IR spectrum (KBr), ν, cm-1: 3191 (OH), 3093 (CH), 2959 (CH), 2889 (CH), 1648 (C=N), 976
1
(N–O). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 10.43 (2H, s, NOH); 3.34 (2H, s, C(2)H2); 2.14 (4H, s,
726

C(4)H2, C(6)H2); 0.85 (6H, s, CH3). 13C NMR spectrum (DMSO-d6), δ, ppm: 152.59 (C(1), C(3)); 43.86 (C(4), C(6));
31.69 (C(5)); 27.37 (CH3); 23.15 (C(2)). Found, %: C 56.42; H 8.82; N 15.83. C8H14N2O2. Calculated, %: C 56.45;
H 8.29; N 16.46.
1-(2-Methyl-1-vinyl-3-pyrrolyl)ethanone O-Vinyloxime (2a). A mixture of dioxime (1a) (1.95 g,
15.0 mmol) and finely powdered KOH.0.5 H2O (0.84 g, 12.9 mmol) in DMSO (100 ml) was saturated in an
autoclave (0.5 liter) with acetylene (initial pressure 14 atm) at room temperature. The reaction mixture was
heated to 100°C, maintained at this temperature for 1 h, then cooled. Water (100 ml) was added, and the mixture
extracted with ether (4 × 40 ml). The total ether extract was washed with water (3 × 30 ml), and dried over
K2CO3. After removing the ether, the red liquid was chromatographed on a column (basic Al2O3, hexane) and
product 2a (0.32 g, 11%) was isolated as a clear light yellow liquid as a mixture of E- and Z-isomers (1:2),
nD20 1.5668. IR spectrum (film), ν, cm-1: 3115 (CH), 3069 (CH), 3048 (CH), 2923 (CH), 1640 (C=C), 1602
1
(pyrrole ring), 1555 (pyrrole ring), 1307 (C–N), 1191 (C–O), 993 (N–O). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): (1H, dd, 3JBX = 14.3, 3JAX = 6.7, HX); 6.90 (1H, dd, 3JB'X' = 15.6, 3JA'X' = 8.9, HX'); 6.88 (1H, d, 3J4',5' = 3.2,
H-5'); 6.25 (1H, d, 3J4',5' = 3.2, H-4'); 5.13 (1H, dd, 2JA'B' = -0.8, HB'); 4.75 (1H, dd, 3JAX' = 8.9, HA'); 4.56 (1H, dd,
2JAB = -1.4, HB); 4.05 (1H, dd, 3JAX = 6.7, HA); 2.47 (3H, s, C(2)H3); 2.21 (3H, s, N=C–CH3). 13C NMR spectrum
(CDCl3), δ, ppm: 155.22 (C=N); 152.81 (C(α)); 130.47 (C(α')); 127.89 (C(2)); 117.96 (C(3)); 115.99 (C(5)); 109.98
(C(4)); 100.08 (C(β')); 87.30 (C(β)); 15.21 (N=C–CH3); 11.96 (2-CH3). Found, %: C 69.20; H 7.62; N 14.61.
C11H14N2O. Calculated, %: C 69.45; H 7.42; N 14.72.
1,1'-Divinyl-2'-methyl[2,3']bipyrrole (3). The reaction mixture obtained as described above was
heated to 120°C and maintained at this temperature for 1 h. After processing analogously to that described
above and removing the ether from the residue (dark-red resinous mass) product 3 (0.21 g, 7%) was isolated by
column chromatography (basic Al2O3, hexane), nD20 1.5968. IR spectrum (film), ν, cm-1: 3136 (CH), 3107 (CH),
3036 (CH), 2960 (CH), 2918 (CH), 2866 (CH), 1645 (C=C), 1603 (pyrrole ring), 1559 (pyrrole ring), 1323
1
(C–N). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.08 (1H, dd, J3,5 = J4,5 = 3.2, H-5); 6.97 (1H, d, J4',5' = 3.1,
3
3
3
3
H-5'); 6.88 (1H, dd, JB'X' = 15.8, JA'X' = 8.9, HX'); 6.85 (1H, dd, JBX = 15.9, JAX = 9.0, HX); 6.27 (1H, t,
J
3,4 = 3.2, H-4); 6.17 (1H, d, J4',5' = 3.1, H-4'); 6.05 (1H, dd, J3,4 = 3.2, H-3); 5.13 (1H, dd, 2JA'B' = -1.1, HB'); 5.06
2
3
3
(1H, dd, JAB = -0.9, HB); 4.71 (1H, dd, JA'X' = 8.9, HA'); 4.56 (1H, dd, JAX = 9.0, HA); 2.20 (3H, s, CH3).
13C NMR spectrum (CDCl3), δ, ppm: 131.86 (C(α)); 130.60 (C(α')); 128.84 (C(2)); 127.75 (C(2')); 116.17 (C(5));
115.50 (C(5')); 113.32 (C(3')); 112.03 (C(4')); 109.86 (C(4)); 109.77 (C(3)); 98.52 (C(β')); 96,74 (C(β)); 10.60 (CH3).
Found, %: C 78.46; H 6.90; N 14.05. C13H14N2. Calculated, %: C 78.75; H 7.12; N 14.13.
2-Methyl-1-vinyl-3-pyrrolyl Phenyl Ketone O-Vinyloxime (2b), 2-Methyl-1-vinyl-3-pyrrolyl Phenyl
Ketone (5), 3-Methyl-5-phenylisoxazole (6a), and 5-Methyl-3-phenylisoxazole (6b). A mixture of dioxime 2a
(4.00 g, 20.8 mmol) and finely powdered KOH·0.5 H2O (2.71 g, 41.7 mmol) in DMSO (50 ml) was saturated
with acetylene. The mixture was then rapidly heated and maintained at 100°C for 5 min. After working up, the
residue after removal of the ether was chromatographed on a column (basic Al2O3, hexane–ether, 3:1). Pyrrole
2b (0.20 g, 4%) (clear amber liquid), pyrrole 5 (0.55 g, 13%) (clear viscous amber liquid), and a mixture of
isoxazoles 6a and 6b (0.59 g, 18%) (clear viscous amber liquid) were isolated.
24
Oxime 2b. nD 1.6010. IR spectrum (film), ν, cm-1: 3114 (CH), 3061 (CH), 2918 (CH), 2860 (CH),
1642 (C=C), 1603 (pyrrole ring), 1591 (Ph), 1572 (pyrrole ring), 1495 (Ph), 1308 (C–N), 1172 (C–O), 989
1
(N–O). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.58 (2H, m, HPh-o); 7.39 (1H, m, HPh-p); 7.34 (2H, m,
3
3
3
3
HPh-m); 7.05 (1H, dd, JBX = 14.1, JAX = 6.7, HX); 7.00 (1H, d, J4',5' = 3.1, H-5'); 6.88 (1H, dd, JB'X' = 15.5,
3JA'X' = 8.9, HX'); 6.24 (1H, d, J4',5' = 3.1, H-4'); 5.17 (1H, dd, JA'B' = -0.8, HB'); 4.77 (1H, dd, JA'X' = 8.9, HA');
3
2
3
4.67 (1H, dd, JAB = -1.4, HB); 4.15 (1H, dd, JAX = 6.7, HA); 2.02 (3H, s, CH3). 13C NMR spectrum (CDCl3),
δ, ppm: 155.65 (C=N); 152.95 (C(α)); 136.45 (CPh-i); 130.22 (C(α')); 129.91 (C(2)); 129.74 (CPh-p); 128.50 (CPh-o);
128.32 (CPh-m); 115.98 (C(5)); 113.99 (C(3)); 111.70 (C(4)); 99.66 (C(β')); 88.07 (C(β)); 12.19 (CH3). Found, %:
C 76.37; H 6.10; N 10.95. C16H16N2O. Calculated, %: C 76.16; H 6.39; N 11.10.
2
3
727

Ketone 5. nD22 1.6170. IR spectrum (film), ν, cm-1: 3116 (CH), 3057 (CH), 3027 (CH), 2921 (CH), 1639
1
(C=C and C=O), 1598 (pyrrole ring), 1577 (pyrrole ring), 1500 (Ph), 1311 (C-N). H NMR spectrum (CDCl3),
3
3
δ, ppm (J, Hz): 7.81 (2H, m, HPh-o); 7.47 (3H, m, HPh-m, HPh-p); 6.98 (1H, dd, JB'X' = 15.5, JA'X' = 8.8, HX');
3
3
2
6.91 (1H, d, J4',5' = 3.0, H-5'); 6.43 (1H, d, J4',5' = 3.0, H-4'); 5.28 (1H, dd, JA'B' = -0.8, HB'); 4.94 (1H, dd,
3JA'X' = 8.8, HA'); 2.60 (3H, s, CH3). 13C NMR spectrum (CDCl3, δ, ppm: 192.40 (C=O); 140.40 (CPh-i); 135.95
(C(2)); 131.28 (CPh-p); 129.70 (C(α)); 129.17 (CPh-o); 128.08 (CPh-m); 121.47 (C(3)); 115.77 (C(5)); 113.40 (C(4));
102.22 (C(β)); 11.42 (CH3). Found, %: C 79.88; H 6.86; N 6.75. C14H13NO. Calculated, %: C 79.59; H 6.20; N
6.63.
Mixture of Isoxazoles 6a and 6b (1:1). Mp 32°C. IR spectrum (film), ν, cm-1: 3130 (CH), 3057 (CH),
2926 (CH), 2855 (CH), 1642 (isoxazole ring), 1610 (isoxazole ring), 1593 (Ph), 1575 (Ph), 1502 (Ph).
1
Found, %: C 76.26; H 6.10; N 9.03. C10H9NO. Calculated, %: C 75.45; H 5.70; 8.80. H NMR spectrum
(CDCl3), δ, ppm, mixture: compound 6a 7.76 (2H, m, HPh-o); 7.44 (3H, m, HPh-m, HPh-p); 6.37 (1H, s, H-4);
2.36 (3H, s, CH3); compound 6b 7.79 (2H, m, HPh-o); 7.46 (3H, m, HPh-m, HPh-p); 6.30 (1H, s, H-4); 2.48 (3H, s,
CH3). 13C NMR spectrum (CDCl3), δ, ppm, mixture: compound 6a 169.59 (C(5)); 160.36 (C(3)); 129.97 (CPh-p);
128.91 (CPh-m); 127.56 (CPh-i); 125.72 (CPh-o); 100.17 (C(4)); 11.53 (CH3); compound 6b 169.88 (C(5)); 162.52
(C(3)); 129.79 (CPh-p); 128.84 (CPh-m); 126.89 (CPh-i); 126.71 (CPh-o); 12.33 (CH3).
4-Ethyl-3,5-dipropylisoxazole (7). A mixture of dioxime 1c (1.00 g, 4.7 mmol), finely powdered
KOH·0.5 H2O (0.61 g, 9.3 mmol), and water (0.9 g, 50 mmol) in DMSO (15 ml) was stirred at 100°C for 2 h.
After cooling, water (30 ml) was added, and the mixture was extracted with ether (4 × 10 ml). The total ether
extract was washed with water (3 × 10 ml), and dried over K2CO3. After removing the ether, the residue was
column chromatographed (basic Al2O3, ether) and isoxazole 7 (0.21 g, 25%) (clear colorless liquid) and initial
dioxime 1c (0.24 g, 24%) were isolated. Isoxazole 7. nD21 1.4592. IR spectrum (film), ν, cm-1: 2964 (CH), 2936
1
3
(CH), 2873 (CH), 1630 (isoxazole ring). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.61 (2H, t, Jα,β = 7.5,
3
3
α-CH2 in Pr); 2.55 (2H, t, Jα,β = 7.6, α-CH2 in Pr); 2.31 (2H, q, Jα,β = 7.6, CH2 in Et); 1.70 (4H, m, β-CH2 in
3
3
Pr); 1.08 (3H, t, CH3 in Et); 0.99 (3H, t, Jβ,γ = 7.4, CH3 in Pr); 0.94 (3H, t, Jβ,γ = 7.4, CH3 in Pr). 13C NMR
spectrum (CDCl3), δ, ppm: 167.96 (C(5)); 162.90 (C(3)); 114.64 (C(4)); 27.54 (CPr-α); 27.28 (CPr-α); 21.33 (CEt-α);
15.44 (CEt-β, CPr-β); 15.13 (CPr-β); 14.11 (CPr-γ); 13.86 (CPr-γ). Mass spectrum, m/z (Irel, %): 181 (2) [M]+; 166 (37)
[M-Me]+; 152 (77) [M-Et]+; 138 (100) [M-Pr]+; 124 (18); 110 (49); 96 (33). Found, %: C 72.75; H 10.20; N
7.90. C11H19NO. Calculated, %: C 72.88; H 10.56; N 7.73.
The work was carried out with the financial support of the Russian Fund for Fundamental Investigations
(Project Nos. 03-03-32472 and 2241.2003.3) and of the Presidium of the Russian Academy of Sciences (Project
No. 10002-251/P-25/155-305/200404-072).
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