(R)-4-menthen-3-one anti-oxime and its transformation under Beckman rearrangement conditions

Article abstract of DOI:10.1023/B:CONC.0000018111.69227.fb

(R)-4-Menthenone anti-oxime was synthesized for the first time. Its transformations under Beckman rearrangement conditions were studied.

Full text of DOI:10.1023/B:CONC.0000018111.69227.fb

Chemistry of Natural Compounds, Vol. 39, No. 6, 2003
( )-4-MENTHEN-3-ONE
R
-OXIME AND ITS TRANSFORMATION
anti
UNDER BECKMAN REARRANGEMENT CONDITIONS
R. Ya. Kharisov,1 E. R. Latypova,2 R. F. Talipov,2
R. R. Muslukhov,1 G. Yu. Ishmuratov,1
and G. A. Tolstikov1
UDC 542.952.3+547.388.4+547.596.4
(R)-4-Menthenone anti-oxime was synthesized for the first time. Its transformations under Beckman
rearrangement conditions were studied.
Key words:
-oxime, Beckman rearrangement, ( )-4-menthenone, ( )-3,7-dimethyl-6-oxooctanoicacidmethylester,
R S
anti
Semmler—Wolf reaction.
The synthesis of a totally optically pure chiral unit that was based on ozonolytic decyclization of ( )-4-menthenone
R
(1) was reported previously [1, 2]. In order to expand the use of 1, we prepared its oxime 2 (Scheme 1), which was synthesized
previously[3] bythe reaction of racemic menthene and nitrosyl chloride with subsequent dehydrochlorination. It was proposed
to have the
-configuration. However, the stereochemistryof the ketoxime could not be unambiguously determined using the
syn
traditional Beckman rearrangement. The
-structure of the oxime was confirmed only later [4].
syn
NH OH HCl
2
OH
O
Py
N
1
2
Scheme 1.
A comparison of the mp (57-58°C) and UV spectrum (EtOH, λ
232 nm, log ε 3.55) of 2 synthesized byus with data
max
for the compound prepared earlier (mp 66-67°C, λ
242 nm, log ε 4.1 [4]) showed that they differ substantially.
max
Based on these differences and the fact that
-oximes usually have higher melting points [5], we assigned the
-
syn
anti
configuration of the hydroxyl and double bond to our 2. Furthermore, it is known that
-oximes, with rare exceptions, either
anti
decompose to tars or do not react under Beckman-rearrangement conditions [6]. Oxime 2 would be converted to
tetrahydroazepinone 3 through a successful reaction. However, it did not rearrange upon treatment with thionyl chloride and
decomposed upon treatment with P O and conc. H SO . Use of the Beckman mixture (Ac O—AcOH—HCl) at various
2
5
2
4
2
temperatures (20 and 100°C) produced the O-acyl derivative 4 and the product of its further aromatization, acetamide 5. This
can be explained by the initial formation of 4, which then was transformed further (according to Semmler—Wolf) into amine
6 with subsequent acylation to 5 (Scheme 2).
1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, fax: (3472) 35 60 66, e-mail: kharis@anrb.ru; 2) Bashkir State University, 450074, Ufa, ul. Frunze, 32, fax: (3472)
226105, e-mail: TalipovRF@bsu.bashedu.ru. Translatedfrom KhimiyaPrirodnykh Soedinenii, No. 6, pp. 470-472, November-
December, 2003. Original article submitted November 3, 2003.
0009-3130/03/3906-0569$25.00 ©2003 Plenum Publishing Corporation
569

O
SOCl
2
OH
100°C
H
N
NHAc
N
3
2
5
Ac O
2
AcOH - HCl
20°C
NOCOCH
3
NH
2
4
6
-AcOH
+
-H
H
H
+
+H
N
N
H
H
N
H
Scheme 2.
The majority of oxime arylsulfonates are exceedingly reactive compounds that undergo the Beckman rearrangement
during synthesis [7]. However, reaction of 2 with p-toluenesulfonyl chloride produced O-tosyl derivative 7, which was
unreactive toward several traditional reagents, for example, aluminum oxide [8] and NaOH (in THF—H O) [9]. Also, heating
2
(100°C) in MeOH formed a complicated mixture from which we isolated using column chromatography (S)-3,7-dimethyl-6-
oxooctanoic acid methyl ester (8) in 70% yield (Scheme 3). Compound 8 was identical to that prepared previously by us from
menthone through an intermediate Baeyer—Villager reaction [10].
CO Me
MeOH
100°C
TsCl
Py
2
OH
O
N
NOTs
7
2
8
(or NaOH)
Al O
2
3
3
Scheme 3.
The proposed reaction mechanism is consistent with already known transformations of oxime tosylates [7]
(Scheme 4).
CO Me
2
−
OMe
+
H O
2
∆
MeO
8
NH
N
2
+
N
NOTs
N
7
Scheme 4.
570

Thus, we prepared for the first time theanti-oxime ofopticallypure menthenone. For this, theBeckman rearrangement
could be used successfully only for the corresponding tosylate. The reaction occurs with deazotization, giving ketoester 8.
EXPERIMENTAL
IR spectra were recorded on a Specord M-82 instrument as thin layers. NMR spectra (δ, ppm, J/Hz) were obtained on
13
a Bruker AM-300 spectrometer (working frequency 300.13 MHz for PMR and 75.47 MHz for C) in CDCl relative to TMS.
3
Signals in PMR spectra were assigned and spin—spin coupling constants (SSCC) were determined using double resonance and
two-dimensional correlation spectroscopy (COSY-H-H). Mass spectra were measured in an MX-1320 instrument at ionizing
potential 70 eV. UV spectra were recorded on a Specord M400 instrument. Chromatographic analysis was performed on a
Chrom-5 instrument [column length, 2.4 m; stationary phase, PEG-6000 (5%) on Inerton AW-DMCS (0.125-0.160 mm);
workingtemperature50-200°C]withHecarrier gas. Opticalrotationsweremeasuredon aPerkin—Elmer-241-MCpolarimeter.
Solvents were dried as usual. Column chromatography was performed over SiO (L, 60-200 µm, Lancaster, England). TLC
2
monitoring was carried out over SiO (Silufol, Czech Rep.). Petroleum ether (PE) (bp 40-70°C) was used for chromatography.
2
Elemental analyses of all compounds agreed with those calculated.
(R)-5-Methyl-2-(1-methylethyl)-2-cyclohexen-1-one Oxime (2). A solution of 1 (2.00 g, 13.2 mmol) in Py(22 mL)
was stirred (20°C) and treated with NH OH·HCl (4.40 g, 55.7 mmol). After 1 h the reaction mixture was diluted with
2
ethylacetate (50 mL), washed with H O (2 × 50 mL), dried over Na SO , and evaporated. The solid was recrystallized from
2
2
4
19
aqueous EtOH (50%) to afford 2 (1.66 g, 77%) as white crystals, C H NO, mp 57-58°C, [α]
-47.9° (c 9.99, CHCl ),
3
10 17
D
R 0.6 (PE:MeO-t-Bu, 2:1).
f
UV spectrum (EtOH, λ , nm): 232 (log ε 3.55) [4].
max
-1
IR spectrum (KBr, ν, cm ): 964 (N–O), 1636 (C N), 3268 (O–H).
PMR (δ, ppm, J/Hz): 1.01 (d, 3H, J = 5.5, CH C-5), 1.07 [d, 6H, J = 6.9, (CH ) C], 1.70-1.90 (m, 2H, H -4, H-5), 1.92
3
3 2
a
2
3
2
(d, 1H, J = 13.3, H -6), 2.23 (dd, 1H, J = 13.8; J = 9.0, H -4), 2.80 (sept., 1H, J = 6.9, HCC-2), 3.12 (d, 1H, J = 13.3, H -6),
a
e
e
6.01 (d, 1H, J = 4.5, H-3), 9.30 (br.s, 1H, O–H).
13
C NMR (δ, ppm): 21.27 (CH C-5), 21.29 and 22.39 [(CH ) C], 27.03 (C-8), 27.78 (C-5), 30.81 (C-4), 33.42 (C-6),
3
3 2
129.19 (C-3), 140.14 (C-2), 155.51 (C-1).
(R)-5-Methyl-2-(1-methylethyl)-2-cyclohexen-1-one Tosylate Oxime (7). A mixture of 2 (0.35 g, 2.1 mmol) and
dry Py (10 mL) at 0 C was treated with p-TsCl (0.44 g, 2.3 mmol), stirred and heated to room temperature, and left for 18 h.
The Py was evaporated in vacuum. The solid was dissolved in H O (10 mL) and extracted with CH Cl (3 × 30 mL). The
2
2
2
extract was washed successively with H O and saturated NaCl and NaHCO solutions, dried over MgSO , and evaporated to
2
3
4
afford crude product (0.56 g), recrystallization of which from aqueous EtOH (50%) isolated 7 (0.51 g, 76%) as white crystals,
18
mp 95.5-96.5 C, R 0.63 (PE:MeO-t-Bu, 2:1), [ ]
-20.4° (c 1.57, CHCl ).
3
f
D
-1
IR spectrum (KBr, ν, cm ): 952 (N–O); 1192, 1366 (S=O); 1492, 1594 (C=C); 1636 (C–N).
3
3
PMR (δ, ppm, J/Hz): 0.96 (d, 3H, J = 5.5, H CC-5), 0.99 [d, 6H, J = 5.9, (CH ) C], 1.70-1.83 (m, 2H, H -4, H-5),
3
3 2
a
2
2
3
3
1.94 (d, 1H, J = 12.9, H -6), 2.25 (dd, 1H, J = 15.3, J = 7.2, H -4), 2.44 (s, 3H, H C-Ar), 2.76 (g, 1H, J = 5.9, HCC-2), 6.19
a
e
3
3
(dd, 1H, J = 6.2, J = 2.3, H-3), 7.33 and 7.89 (both d, 4H, J = 8.3, H-Ar).
Beckman Rearrangement Methods. Preparation of 4, 5, and 8.
A. Dry HCl was bubbled through a solution of 2 (0.64 g, 3.8 mmol) in a mixture of glacial AcOH (3.7 mL) and Ac O
2
(1.85 mL) at 20°C for 1 h. The reaction mixture was left for 43 h, treated with H O (10 mL), extracted with CH Cl (3 ×
2
2
2
20 mL), dried over MgSO , and evaporated. The solid (0.70 g) was chromatographed over SiO (eluent PE:MeO-t-Bu, 10:1)
4
2
to afford 4 (0.45 g, 64%).
B. Dry HCl was bubbled until saturated (45 min) through a solution of 2 (1.00 g, 5.99 mmol) in a mixture of glacial
AcOH (9.52 mL, 9.99 g, 1.667 mmol) and Ac O (1.85 mL, 19.6 mmol) in a glass ampul. The ampul was sealed and heated
2
for 3 h on a boiling-water bath. The reaction mixture was left for 48 h at room temperature, diluted with H O (5 mL), and
2
extracted with Et O (3 × 30 mL). The extract was washed with saturated NaHCO solution (until the pH was 7), dried over
2
3
MgSO , and evaporated. The solid (0.94 g) was chromatographed over SiO (eluent PE:MeO-t-Bu, 10:1) to afford 5 (0.25 g,
4
2
27%).
571

C. A solution of 7 (2.53 g, 7.88 mmol) in absolute MeOH (50 mL) was heated in an ampul for 4.5 h on a boiling-water
bath, evaporated in vacuum, treated with aqueous NaOH solution (10%, until the pH was ~10), extracted with CH Cl , dried
2
2
over Na SO , and evaporated. The solid (1.58 g) was chromatographed (eluent PE:CH Cl , 5:1) to afford 8 (1.10 g, 70%) [10].
2
4
2
2
24
(R)-6-[(Acetyloxy)imino]-4-methyl-1-isopropylcyclohex-1-ene (4). R 0.56 (PE:MeO-t-Bu, 2:1), [α]
-52.8° (c
f
D
3.08, CHCl ), C H NO .
3
12 19
2
-1
IR spectrum (KBr, ν, cm ): 1640 (C=C), 1685 (C=N), 1775 (C=O).
3
PMR (δ, ppm, J/Hz): 0.93 (d, 3H, J = 5.4, CH C-5), 1.03 [d, 6H, J = 6.9, (CH ) C], 1.70-1.85 (m, 2H, H -4, H-5),
3
3 2
a
2
2
3
2
1.90 (d, 1H, J = 11.8, H -6), 2.23 (dd, 1H, J = 12.8, J = 6.3, H -4), 2.18 (s, 3H, CH CO), 3.03 (d, 1H, J = 11.8, H -6), 6.18
a
e
3
e
(d, 1H, J = 4.3, H-3).
13
C NMR (δ, ppm): 19.81 (CH CO), 20.94 and 21.81 [(CH ) C], 22.18 (CH C-5), 26.97 (HCC-2), 27.67 (C-5), 32.24
3
3 2
3
(C-4), 33.24 (C-6), 133.15 (C-3), 139.97 (C-2), 161.31 (C-1), 169.60 (C=O).
+
+
+
Mass spectrum (EI, 70 eV, m/z, I , %): 209 (0.8) [M] , 167 (3) [M - CH CO] , 150 (32) [M - CH COO] , 148 (19),
rel
2
3
+
134 (54), 107 (54), 94 (21), 93 (23), 91 (14), 81 (17), 79 (21), 77 (18), 67 (31), 65 (11), 55 (20), 53 (20), 43 (100) [CH CO] ,
3
42 (22), 41 (69), 39 (35), 27 (33).
5-Methyl-2-isopropylacetanilide (5). R 0.36 (CH Cl ).
f
2
2
-1
IR spectrum (KBr, ν, cm ): 1490, 1600 (C=C); 1555, 3310 (N–H); 1685 (C=O).
PMR (δ, ppm, J/Hz): 1.20 [d, 6H, J = 6.72, (CH ) C], 2.17 (s, 3H, CH CO), 2.30 (s, 3H, CH C-5), 2.96-3.08 (m, 1H,
3 2
3
3
HC), 6.93-7.21 (m, H-Ar).
13
C NMR (δ, ppm): 19.55 (CH CO), 20.83 (CH C-5), 23.15 and 23.91 [(CH ) C], 27.58 (HC), 125.41 (C-3), 126.11
3
3
3 2
(C-6), 127.18 (C-4), 133.61 (C-1), 135.85 (C-5), 138.41 (C-2), 169.05 (C=O).
18
(S)-3,7-Dimethyl-6-oxooctanoic acid methyl ester (8). R 0.5(PE:MeO-t-Bu, 2:1), [α]
+9.5°(c 0.16, CHCl )[10].
3
f
D
The IR spectrum is practically identical to that described previously [10].
3
3
PMR (δ, ppm, J/Hz): 0.95 (d, 3H, J = 6.6, CH C-3), 1.09 [d, 6H, J = 6.9, (CH ) C], 1.40-1.54 (m, 1H, H-4), 1.56-1.68
3
3 2
2
3
2
3
(m, H, H′-4), 1.87-2.00 (m, 1H, H-3), 2.13 (dd, 1H, J = 14.8, J = 8.1, H′-2), 2.31 (dd, 1H, J = 14.8, J = 5.9, H-2), 2.43-2.50
(m, 2H, H-5), 2.61 (g, 1H, H-7), 3.68 (s, 3H, CH O).
3
13
C NMR (δ, ppm): 18.26 [(CH ) C-6], 19.51 (CH C-3), 30.01 (C-3), 30.29 (C-4), 37.81 (C-5), 40.84 (C-7), 41.39
3 2
3
(C-2), 51.45 (CH O), 173.36 (C-1), 214.49 (C-6).
3
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