Synthesis and crystal and molecular structure of a pulegone isoxazole derivative

Full text of DOI:10.1007/s10600-005-0089-8

Chemistry of Natural Compounds, Vol. 41, No. 1, 2005
SYNTHESIS AND CRYSTAL AND MOLECULAR STRUCTURE
OF A PULEGONE ISOXAZOLE DERIVATIVE
D. T. Sadyrbekov,1 G. A. Atazhanova,1 A. T. Kulyyasov,1
V. A. Raldugin,2 I. Yu. Bagryanskaya,2 Yu. V. Gatilov,2
UDC 547.913+548.737
1
1
1
T. T. Edil
baeva, K. M. Turdybekov, and S. M. Adekenov
We continued work on chemical transformations of pulegone (1), which we have used previously in the two-step
synthesis of its pyrazole derivative [1] that is analogous to the pyrazole derivative of artemisin ketone [2], in order to prepare
biologically active compounds.
Compound 1 is a monocyclic unsaturated monoterpenoid of the paramenthane series and the principal component of
Ziziphora clinopodioides
Mentha longifolia
essential oils of
Lam. (47-60% pulegone content) [3] and
L. (40-70% pulegone
content) [4].
4(8)
∆
-p-Menthen-3-one (pulegone, 1)
Z. clinopodioides
was isolated by vacuum fractionation of
essential oil, bp 94-
26.3
+23.94° (c 0.026, CHCl ).
95.5 C/10 mm Hg, [α]
D
3
2,2,6-Trimethyl-1-oxaspiro[2,5]octan-4-one (pulegone epoxide, 2) was prepared by the following method [5]: 1
(5 g) was dissolved in MeOH (40 mL), treated with H O (5 mL), stirred, and treated in small portions over 1 h with NaOH
2
2
solution (3.75 mL, 4%). The reaction mixture was extracted three times with ether. The combined extracts were dried over
20
MgSO and evaporated in vacuo to produce 2 (4 g, 80%) as colorless crystals, mp 43-45°C, [α]
+10.28° (c 0.020, CHCl ).
3
4
D
10
.
H2O2, NaOH
MeOH
5
NH2OH HCl
7
7a
MeOH
O
1
O
N
HO
O
O
2
8
9
1
3
2
3,3,6-Trimethyl-4,5,6,7-tetrahydrobenz[c]isoxazol-3a-ol. Compound 2 (1 g) was dissolved in MeOH (5 mL) and
treated with NH OH·HCl (5 g) and CH COONa (10 g) dissolved in distilled water (15 mL). The resulting mixture was refluxed
2
3
for 1 h. The product was precipitated byadding a large amount of cold water. The resulting crystals were separated byfiltration
and recrystallized from alcohol to give 3 (0.86 g, 86%) as colorless crystals, C H NO , mp 138-139.5° (CHCl ),
10 17
2
3
15.6
[α]
+3.31° (c 0.016, CHCl ).
3
D
PMR spectrum (δ, ppm, J/Hz): 1.78 (ddd, H-4a, J = 14.0, J = 3.0, J = 3.0), 1.66 (m, H-4b, overlaps with H-5a), 1.64
(m, H-5a, overlaps with H-4b), 1.49 (m, H-5b, overlaps with H-6), 1.54 (m, overlaps with H-5b), 2.61 (br.d, H-7a, J = 14.5),
2.02 (dd, H-7b, J = 14.5, J = 12.0), 1.35 (s, 3H), 1.14 (s, 3H), 1.04 (d, 3H, J = 6.0), 1.97 (br.s, OH).
13
C NMR spectrum (δ, ppm): 85.81 (s, C-3), 83.47 (s, C-3a), 30.76 (t, C-4), 29.35 (t, C-5), 32.32 (d, C-6), 30.97 (t,
C-7), 161.41 (s, C-7a), 23.52 (q, C-8), 19.68 (q, C-9), 21.72 (q, C-10).
1) Institute of Phytochemistry, Ministry of Education and Science, Republic of Kazakhstan, 470032, Karaganda, ul.
Gazalieva, 4, fax(3212)433773, e-mail:arglabin@phyto.kz;2) Novosibirsk Institute ofOrganic Chemistry, Siberian Division,
Russian Academy of Sciences, 630090 Novosibirsk, pr. Akad. Lavrent eva, 9, fax (3832)-34-47-52, e-mail:
raldugin@nioch.nsc.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 83-84, January-February, 2005. Original
article submitted November 1, 2004.
0009-3130/05/4101-0103 ©2005 Springer Science+Business Media, Inc.
103

C 8
O 1
C 3
C 3 A
C 4
C 9
C 5
O 2
C 7 A
C 6
N 1
C 7
C 1 0
Fig. 1. Molecular structure of the pulegone isoxazole derivative from XSA.
The molecular structure of 3 was determined by an x-ray structure analysis (XSA) (Fig. 1). Cell constants and
intensities of 1160 reflections from 3 were measured on a Syntex P2 diffractometer at 20 C (Cu Kα, graphite monochromator,
1
θ/2θ-scanning, 2θ ≤ 140.26°). The crystals are orthorhombic, a = 5.7560(12), b = 10.811(2), c = 16.584(3) Å, V = 1032.0(4)
3
3
Å , d
= 1.179 g/cm , Z = 4 (C H NO ), space group P2 2 2 . The structure was solved by direct methods using the
10 17 2 1 1 1
calc
SHELXS-97programs. Nonhydrogen atoms were refined byfull-matrix anisotropic least-squares methods; Hatoms foundfrom
a difference synthesis, isotropically using the SHELXL-97 programs. The final agreement factors were R = 0.0366 and
wR = 0.0860 for 1013 independent reflections with I ≥ 2σ.
Figure 1 shows that the six- and five-membered rings are fused in a pseudotrans manner (torsion angles
3
C3C3aC7aN1 = -16.7°, C7C7aC3aC4 = 41.2°). The conformation of the five-membered ring is a 3α-envelope ( C = 1.4,
S
C3a, C7a, N1, and O2 are coplanar within ±0.008 Å, C3 deviates from this plane by 0.41 Å to the α-side). The C3a hydroxyl
65
has the β-orientation. The conformation of the six-membered ring is a distorted chair (∆C = 3.3°). The C6 methyl has the
2
β-orientation. Based on these data, the structure 3,3,6-trimethyl-4,5,6,7-tetrahydrobenz[c]isoxazol-3a-ol is proposed for 3.
The XSA data were deposited as a CIF file in the Cambridge Crystallographic Database (CCDC 263000).
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