Opening of the A ring in taraxast-20(30)-en-3-one oxime in the Beckmann reaction

Full text of DOI:10.1134/S1070428009040265

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 4, pp. 621–623. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.R. Akhmetova, E.R. Shakurova, L.M. Khalilov, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4,
pp. 634–636.
SHORT
COMMUNICATIONS
Opening of the A Ring in Taraxast-20(30)-en-3-one Oxime
in the Beckmann Reaction
V. R. Akhmetova, E. R. Shakurova, and L. M. Khalilov
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received February 29, 2008
DOI: 10.1134/S1070428009040265
Cytotoxic, antibacterial, and fungicidal activity of
aza terpenoids [1–5] stimulated synthesis of nitrogen-
containing taraxastanes on the basis of 3β-hydroxy-
oximes E-III and Z-III failed to undergo Beckmann
rearrangement in the presence of p-toluenesulfonyl
chloride, whereas the reaction in the presence of thi-
onyl chloride in anhydrous dioxane was accompanied
by cleavage of the A ring with formation of nitrile IV.
Syntheses of nitriles from oximes containing electron-
2
0(30)-taraxast-20(30)-ene (I) which was isolated by
us from the Scotch thistle Onopordum acanthium L.
according to the procedure described in [6]. As key
stage we selected Beckmann rearrangement of cyclic
ketone oximes to lactams with ring expansion. For this
purpose we synthesized 3-oxo derivative II by oxida-
tion of alcohol I with pyridinium chlorochromate
withdrawing groups (OH, NH ) in the α-position via
2
trans-elimination of water (abnormal Beckmann rear-
rangement) have been reported [9]; nitriles were also
formed together with lactams from triterpene
A-oximes having methyl groups in the α-position [10].
(
PCC) in methylene chloride at 25°C (3 h). The forma-
tion of taraxast-20(30)-en-3-one (II) was confirmed by
Nitrile IV was obtained as a 1:2 mixture of (2R)-
and (2S)-stereoisomers whose ratio was determined
3
the presence of a signal at δ 217.0 ppm (C =O) in the
C
1
3
1
3
C NMR spectrum.
from the intentsities of the C (δ 147.0, 113.9 ppm)
C
1
4
13
Neither taraxastane oximes nor their derivatives
and C signals (δ
NMR spectrum. The spectrum also contained a signal
at δ 120.3 ppm, which is typical of cyano group. In
C
146.8 and 114.0 ppm) in the
C
were reported previously. We succeeded in synthesiz-
ing taraxast-20(30)-en-3-one oxime (III) in the pres-
ence of Tseokar-100 zeolite. The reaction of taraxast-
C
1
the H NMR spectrum of IV we observed a multiplet
at δ 2.1–2.4 ppm due to strongly coupled methylene
protons on C in both stereoisomers (2′-Hax/2′-Heq
3′-Hax/3′-Heq system).
2
0(30)-en-3-one (II) with hydroxylamine hydrochlo-
2
′
ride in pyridine gave a mixture of isomeric E- and
/
Z-oximes III at a ratio of 2:1, which was determined
3
from the intensities of the C signals (δ 167.0 and
C
Thus the transformation of ketone oxime III under
the Beckmann rearrangement conditions involves
transannular elimination of water from spatially close
1
66.9 ppm for the E and Z isomers, respectively) in
1
3
the C NMR spectra recorded with a long pulse delay
2
3
24
3
(
10 s) to ensure more complete relaxation [7].
C H , C H , and (E/Z)-C =N–OH groups, leading to
3
3
opening of the A ring and formation of unsaturated
bonds (double C=C and triple C≡N).
Beckmann rearrangement underlies a convenient
method for the preparation of various N-substituted
amides, in particular from ketone oximes derived from
steroids having a carbonyl group in the A ring; for
example, some aza steroids were obtained in such
a way [8]. Beckmann rearrangement of oximes is com-
Taraxast-20(30)-en-3-one (II). A solution of 0.25 g
(0.6 mmol) of compound I in 25 ml of methylene
chloride was quickly added under stirring to a suspen-
sion of 0.41 g (1.8 mmol) of pyridinium chlorochro-
mate in 25 ml of methylene chloride. The mixture was
stirred until the initial compound disappeared (TLC,
EtOAc–C H , 1:10), diluted with 15 ml of chloro-
monly catalyzed by PCl in diethyl ether, concentrated
5
sulfuric acid, thionyl chloride, p-toluenesulfonyl chlo-
ride, and polyphosphoric acid. Isomeric taraxastane
6
14
6
21

6
22
AKHMETOVA et al.
3
0
CH2
CH2
2
9
Me
Me
2
0
1
9
E
E
C
Me
28
Me
i
C
Me
Me
D
Me
D
Me
1
1
0
A
B
Me
A
B
Me
3
HO
O
Me
Me
Me
Me
I
II
CH2
Me
Me
Me
E
ii
iii
C
Me
A
A
+
3' Me
D
Me
HO
NC 2'
N
N
Me
Me
Me
Me
B
Me
HO
Me
H
CH2
Z-III
E-III
(2RS)-IV
2 2 2 2
i: PCC, CH Cl , 3 h; ii: NH OH·HCl, pyridine, 115°C, 2.5 h; iii: SOCl , dioxane, 15 min.
form, and filtered through a layer of silica gel. The
solvent was distilled off, and the residue was subjected
to chromatography on silica gel using hexane–ethyl
acetate (15:1) as eluent. Yield 0.21 g (87%), colorless
with 100 ml of 5% hydrochloric acid, and extracted
with chloroform (3×20 ml). The extract was washed
with a solution of sodium hydrogen carbonate and
dried over calcium chloride, the solvent was distilled
off, and the residue was subjected to chromatography
on silica gel using hexane–ethyl acetate (15 :1) as
eluent. Yield 0.25 g (89%), R 0.41 (C H –EtOAc,
2
0
crystals, mp 128–130°C, [α]D = +78.8° (c = 1.02,
CHCl ), R 0.72 (C H –EtOAc, 5:1). IR spectrum
3
f
6
14
–
1
1
(
KBr), ν, cm : 2910, 1720, 1715. H NMR spectrum,
δ, ppm: 1.04 s (6H, 23-H, 24-H), 0.85 s (3H, 25-H),
f
6
14
–
1
5:1). IR spectrum (KBr), ν, cm : 3300–3150, 1670,
1
0
2
4
.92 s (3H, 26-H), 0.91 s (3H, 27-H), 0.93 s (3H,
1470, 1380. H NMR spectrum, δ, ppm: 1.15 s (6H,
8-H), 0.99 d (3H, 29-H), 0.94–2.01 m (20H, CH ),
23-H, 24-H), 0.804 s (3H, 25-H), 0.90 s (3H, 28-H),
0.926 s (3H, 27-H), 0.94 s (3H, 28-H), 0.98 d (3H,
2
1
3
.48 s and 4.21 s (2H, 30-H). C NMR spectrum, δ ,
C
1
2
3
4
ppm: 39.56 (C ), 33.93 (C ), 217.04 (C ), 39.01 (C ),
5
29-H), 0.96–1.96 m (20H, CH ), 4.63 s and 4.49 s (2H,
2
5
6
7
8
13
5.06 (C ), 19.01 (C ), 33.79 (C ), 40.85 (C ), 49.65
30-H), 9.13 m (1H, NOH). C NMR spectrum, δ ,
C
9
10
11
12
13
1
1
2
(
C ), 36.83 (C ), 20.99 (C ), 26.11 (C ), 38.78 (C ),
ppm: 27.32 (C , E), 26.91 (C , Z), 22.88 (C , E), 23.29
1
4
15
16
17
2
3
3
4
4
2.05 (C ), 27.29 (C ), 38.11 (C ), 34.59 (C ), 48.79
(C , Z), 166.89 (C , E), 167.00 (C , Z), 40.34 (C , E),
39.65 (C , Z), 55.57 (C , E), 55.79 (C , Z), 19.49 (C ,
E), 21.37 (C , Z), 33.76 (C ), 41.78 (C ), 50.08 (C ),
40.92 (C ), 21.60 (C ), 25.87 (C ), 39.34 (C ), 42.16
1
8
19
20
21
4
5
5
6
(
C ), 38.63 (C ), 154.04 (C ), 25.94 (C ), 38.61
2
2
23
24
25
6
7
8
9
(
C ), 25.26 (C ), 23.50 (C ), 15.52 (C ), 15.85
2
6
27
28
29
10
11
12
13
(
C ), 14.48 (C ), 16.53 (C ), 26.01 (C ), 107.25
3
0
14
14
15
16
(
C ). Found, %: C 85.28; H 12.15. C H O. Calculat-
(C , E), 42.05 (C , Z), 27.32 (C ), 37.17 (C ), 34.51
30
48
1
7
18
19
20
ed, %: C 84.84; H 11.39.
Taraxast-20(30)-en-3-one oxime (III, a 1:2 mix-
ture of Z and E isomers). Compound II, 0.28 g
(C ), 46.75 (C ), 36.99 (C ), 154.52 (C ), 25.47
2
1
22
23
23
(
(
(
C ), 39.21 (C ), 25.61 (C , E), 25.52 (C , Z), 21.74
C , E), 22.68 (C , Z), 17.17 (C ), 15.94 (C ), 14.64
C ), 19.49 (C ), 25.87 (C ), 107.16 (C ). Found, %:
2
4
24
25
26
2
7
28
29
30
(
0.65 mmol), was dissolved in 40 ml of anhydrous pyr-
C 82.11; H 11.35; N 3.90. C H NO. Calculated, %:
idine, 0.323 g (4.68 mmol) of hydroxylamine hydro-
chloride was added, the mixture was heated to the
boiling point, 2 g of calcined Tseokar-100 was added,
and the mixture was heated for 2.5 h under reflux with
stirring until the initial compound disappeared (TLC,
EtOAc–C H , 1:10). The mixture was cooled, diluted
30 49
C 81.94; H 11.23; N 3.19.
3-[(2R,S)-2-Isopropenyl-1,4a,4b,6a,10-penta-
methyl-9-methylideneperhydrochrysen-1-yl]pro-
panenitrile (IV, R:S = 2:1). Isomeric oximes III, 0.2 g
(0.44 mmol), were dissolved in 30 ml of anhydrous
6
14
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009

OPENING OF THE A RING IN TARAXAST-20(30)-EN-3-ONE OXIME
623
dioxane, 0.6 ml of freshly distilled thionyl chloride
was added, and the mixture was stirred for 15 min at
room temperature until the initial compound disap-
peared (TLC, EtOAc–C H , 1:10). The solvent was
distilled off, the residue was treated with 10 ml of
water and extracted with chloroform (3×20 ml), the
extracts were combined, washed with water until
neutral reaction, and dried over calcium chloride, the
solvent was removed, and the residue was subjected to
chromatography on silica gel using hexane–ethyl
was measured on a Perkin–Elmer-141 polarimeter. The
melting points were determined on a Boetius melting
point apparatus. The progress of reactions was moni-
tored by TLC on Silufol plates; spots were visualized
by treatment with a solution of 4-methoxybenzalde-
hyde in ethanol. Column chromatography was per-
formed on KSKG silica gel. Pyridinium chlorochro-
mate was prepared according to the procedure de-
scribed in [11].
6
14
acetate (15:1) as eluent. Yield 0.168 g (84%), R 0.66
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f
–
1
(
2
C H –EtOAc, 5:1). IR spectrum (KBr), ν, cm :
235, 1470, 1380. H NMR spectrum, δ, ppm: 1.01 s
6 14
1
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0
(
3H, 16-H), 1.03 s (3H, 17-H), 0.93 s (3H, 18-H),
.95 s (3H, 19-H), 0.99 d (3H, 20-H), 0.92–2.05 m
16H, CH ), 4.23 s and 4.77 s (2H, 21-H, R), 4.23 s
2
2
and 4.87 s (2H, 21-H, S), 2.14–2.41 m (2H, 2-H),
1
3
4
.65 s (2H, 14-H). C NMR spectrum, δ , ppm: 34.74
C
3
′
2′
and 32.48 (C ), 14.06 and 14.76 (C ), 120.31 and
21.20 (C ), 146.87 and 147.01 (C ), 39.36 and 38.78
C ), 21.54 and 23.80 (C ), 33.27 (C ), 40.46 (C ),
0.83 (C ), 46.75 (C ), 21.54 (C ), 26.91 (C ), 39.59
1
′
13
1
(
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(
4
3
(
(
2
3
4
4a
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2a
1
12
11
1
0b
4b
5
6
6a
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1
0a
10
9
8
6. Khalilov, L.M., Khalilova, A.Z., Shakurova, E.R., Nu-
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6.67 (C7 ), 40.81 (C ), 154.51 (C ), 25.63 (C ),
15
6.19 (C ), 22.66 and 22.75 (C ), 114.07 and 113.94
1
4
16
17
18
C ), 17.70 (C ), 16.16 (C ), 14.61 (C ), 19.89
C ), 24.27 (C ), 107.40 (C ). Found, %: C 85.67;
1
9
20
21
H 11.31; N 3.02. C H N. Calculated, %: C 85.44;
3
0
47
H 11.23; N 3.32.
8
The IR spectra were recorded on Specord 75IR
spectrometer from samples dispersed in mineral oil.
9
1
13
The H and C NMR spectra were measured on Jeol
FX 90Q (89.55 and 22.50 MHz, respectively)
and Bruker AMX-300 spectrometers (300.13 and
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7
5.62 MHz, respectively) using CDCl as solvent; the
1966, vol. 2, p. 1718.
3
chemical shifts were determined relative to tetra-
methylsilane as internal reference. The optical rotation
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p. 2647.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 4 2009