Molecular structure of (4Z)-{[(1R,6S)-7,7-dimethyl-2-oxo-3-oxabicyclo [4.1.0] hept-4-en-4-yl]methylene}-2-phenyl-l,3-oxazol-5(4H)-one

Article abstract of DOI:10.1007/s10947-010-0089-9

The (4Z)-{[(1R, 6S)-7,7-dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-yl]methylene}-2-phenyl-1,3-oxazol-5(4H)-one compound is synthesized and its molecular structure is determined.

Full text of DOI:10.1007/s10947-010-0089-9

Journal of Structural Chemistry. Vol. 51, No. 3, pp. 599-602, 2010
Original Russian Text Copyright © 2010 by V. G. Kasradze, E. V. Salimova, F. Z. Galin, O. S. Kukovinets, Z. A. Starikova, and M. Yu. Antipin
MOLECULAR STRUCTURE OF (4Z)-{[(1R,6S)-7,7-
DIMETHYL-2-OXO-3-OXABICYCLO [4.1.0]HEPT-4-EN-
4-YL]METHYLENE}-2-PHENYL-1,3-OXAZOL-5(4ꢀ)-ONE
V. G. Kasradze,1 E. V. Salimova,1 F. Z. Galin,1
UDC 547.597.787
O. S. Kukovinets,1 Z. A. Starikova,2 and M. Yu. Antipin2
The (4Z)-{[(1R,6S)-7,7-dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-yl]methylene}-2-phenyl-1,3-oxazol-
5(4ꢀ)-one compound is synthesized and its molecular structure is determined.
Keywords: oxazolone, formyl enol lactone derivative of ketocaronic acid, Erlenmeyer reaction, single
crystal X-ray diffraction analysis.
Aldehyde condensation with N-acyl glycines under the action of acetic anhydrides (Erlenmeyer reaction) leads to
the formation of 5(4ꢀ)-oxazolones (azlactones) that are convenient synthons for the synthesis of amino acid derivatives.
Aromatic, heterocyclic, and ꢀ,ꢁ-unsaturated aldehydes readily enter into the Erlenmeyer reaction and afford oxazolone with
good yield. However, fatty aldehydes hardly react with acyl glycines, while this reaction with terpene aldehydes has been
poorly studied [1].
We have determined that 4-formyl enol lactone derivative of ketocaronic acid II obtained by successive oxidative
transformations of monoterpene (+)-3-carene I (Fig. 1) can be easily condensed with the hippuric acid in the acetic anhydride
medium [2, 3]. The structure of obtained 5(4ꢀ)-oxazolone III was determined by NMR spectroscopy and single crystal X-ray
diffraction analysis.
Experimental.
(4Z)-{[(1R,6S)-7,7-Dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-yl]methylene}-2-phenyl-1,3-
oxazol-5(4ꢀ)-one III. To the solution of 0.8 g (4.8 mmol) of compound II in 25.8 ml of acetic anhydride we added 0.86 g
(4.8 mmol) of hippuric acid and 0.66 g (4.8 mmol) of potassium carbonate. The reaction mixture was stirred for 5 h, left for
the night, and then it was evaporated. The residue was dissolved in methylene chloride, washed with water, dried with
Na2SO4, evaporated, and chromatographed (SiO2, ethyl acetate: petroleum ether eluent, 4:1). We obtained 1.07 g (72%) of
compound III in the form of light-yellow crystalline substance. ꢀmelt 162ꢂC, [ꢀ]20 31.2ꢂ (s 0.2, CHCl3). 1ꢀ NMR spectrum*
D
(ꢃ/ppm, J/Hz): 1.09 s and 1.35 s (3ꢀ, hem-ꢁꢀ3), 2.04 dd (1ꢀ, H7, J 7.2, 6.0), 2.10 d (1ꢀ, ꢀ8, J 7.2), 6.54 s (1H, H4), 7.0 d
(1ꢀ, 6ꢀ, J 6.0 Hz), 7.45-7.63 m (3ꢀ, ꢀarom), 8.12 d (2ꢀ, ꢀarom, J 8.5 Hz). 13ꢁ NMR spectrum (ꢃ/ppm): 15.97 and 27.03 (hem-
ꢁꢀ3), 25.74 (ꢁ10), 30.80 and 31.08 (ꢁ8, C7), 115.53 (C6), 122.15 (C4), 125.25 (C5), 128.83, 128.83, 129.18, 129.18, 130.31,
134.06 (Carom.), 146.12 (ꢁ3), 165.05, 165.59, 166.54 (ꢁ2, ꢁ1, ꢁ9). Found, %: ꢁ 69.23, ꢀ 4.83, N 4.21. ꢁ18ꢀ15Nꢂ4.
*Numbering of carbon atoms in the NMR spectra corresponds to numbering in the molecular structure shown in
Fig. 2.
1Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences; kasradzevg@anrb.ru.
2A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow. Translated from
Zhurnal Strukturnoi Khimii, Vol. 51, No. 3, pp. 616-619, May-June, 2010. Original article submitted May 18, 2009.
0022-4766/10/5103-0599 © 2010 Springer Science+Business Media, Inc.
599

Fig. 1. Scheme of the synthesis of (4Z)-{[(1R,6S)-7,7-
dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-
yl]methylene}-2-phenyl-1,3-oxazol-5(4ꢀ)-one III.
Fig. 2. Molecular structure of III (thermal ellipsoides are shown with 50% probability).
1
Calculated, %: ꢁ 69.89, ꢀ 4.89, N 4.53. 13ꢁ and ꢀ NMR spectra were measured on a Bruker AM-300 spectrometer
(75.5 MHz and 300 MHz respectively), the internal standard was TMS. The melting temperature was determined on a
Boetius warm stage.
Single crystal X-ray diffraction analysis. Yellow orthorhombic crystals, ꢁ18ꢀ15NO4, (ꢁ = 309.31), at 120 K
a = 6.0246(7) Å, b = 13.3890(16) Å, c = 18.543(2) Å, V = 1495.8(3) Å3, space group ꢂ212121, Z = 4, dx = 1.374 g/cm3. An
experimental set of 15314 reflections was obtained on Bruker SMART 1000 CCD area detector [4] at 120 K (ꢄꢁ0Kꢀ
radiation, ꢅmax = 28.00ꢂ) from a single crystal of 0.55ꢆ0.40ꢆ0.25 mm. After the equivalent reflections were averaged, 3587
independent reflections were obtained (Rint = 0.0381), which were used to interpret and refine the structure. Absorption
( = 0,098 mm–1) was not taken into account.
The structure was solved using the direct method; all non-hydrogen atoms were localized in electron density
difference syntheses and were refined in the in anisotropic approximation against Fh2kl ; all hydrogen atoms were located into
geometrically calculated positions. The final value of uncertainty factors is as follows: R1 = 0.0435 (calculated against Fh2kl
for 3315 reflections with I > 2ꢇ(I)), wR2 = 0.0958 (calculated against Fh2kl for 3587 reflections), GOOF = 1.004, 208 refined
parameters.
All calculations were performed using the SHELXTL PLUS5 software complex [5].
Atom coordinates, torsion angles, and temperature parameters have been deposited with the Cambridge
Crystallographic Data Centre (CCDC No. 711886), and one can get them for free at www.ccdc.cam.uk/conts/retrieving.html
(or from CCDC, 12 Union Road, Cambridge CB2 1EZ; fax: +44 1223 335 033; or deposit@ccdc.cam.ac.uk).
Results and discussion. Single crystal X-ray diffraction analysis of the obtained crystal showed that azlactone III is
formed as an independent isomer with Z-configuration of the exocyclic double bond (Fig. 2). Bond lengths and bond angles
are shown in Tables 1 and 2.
600

TABLE 1. Bond Lengths d, Å in the structure of III
Bond
d
Bond
d
Bond
d
Bond
d
O(1)–C(1)
O(2)–C(2)
O(2)–C(1)
O(3)–C(9)
O(4)–C(9)
O(4)–C(5)
1.197(2)
1.387(2)
1.397(2)
1.203(2)
1.370(2)
1.406(2)
N(1)–C(2)
N(1)–C(3)
C(1)–C(3)
C(2)–C(13)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
1.292(2)
1.402(2)
1.484(3)
1.453(3)
1.344(3)
1.444(3)
1.335(3)
C(6)–C(7)
C(7)–C(10)
C(7)–C(8)
1.465(3)
1.521(2)
1.532(3)
1.475(3)
1.529(2)
1.500(3)
1.510(3)
C(13)–C(14)
C(13)–C(18)
C(14)–C(15)
C(15)–C(16)
C(16)–C(17)
C(17)–C(18)
1.397(3)
1.405(3)
1.391(3)
1.384(3)
1.392(3)
1.382(3)
C(8)–C(9)
C(8)–C(10)
C(10)–C(12)
C(10)–C(11)
TABLE 2. Bond Angles ꢈ, deg in the Structure of III
Angle
Angle
Angle
ꢈ
ꢈ
ꢈ
C(2)–O(2)–C(1)
C(9)–O(4)–C(5)
C(2)–N(1)–C(3)
O(1)–C(1)–O(2)
O(1)–C(1)–C(3)
O(2)–C(1)–C(3)
N(1)–C(2)–O(2)
N(1)–C(2)–C(13)
O(2)–C(2)–C(13)
C(4)–C(3)–N(1)
C(4)–C(3)–C(1)
N(1)–C(3)–C(1)
C(3)–C(4)–C(5)
105.31(14)
122.14(15)
105.38(15)
122.93(18)
132.32(19)
104.74(15)
116.35(16)
127.01(16)
116.58(15)
129.93(17)
121.83(17)
108.16(16)
127.80(17)
C(6)–C(5)–O(4)
C(6)–C(5)–C(4)
O(4)–C(5)–C(4)
C(5)–C(6)–C(7)
C(6)–C(7)–C(10)
C(6)–C(7)–C(8)
C(10)–C(7)–C(8)
C(9)–C(8)–C(10)
C(9)–C(8)–C(7)
C(10)–C(8)–C(7)
O(3)–C(9)–O(4)
O(3)–C(9)–C(8)
O(4)–C(9)–C(8)
122.65(17)
127.99(17)
109.34(15)
122.21(17)
120.95(16)
115.21(16)
60.08(12)
120.17(16)
118.29(16)
59.60(11)
C(12)–C(10)–C(11)
C(12)–C(10)–C(7)
C(11)–C(10)–C(7)
C(12)–C(10)–C(8)
C(11)–C(10)–C(8)
C(7)–C(10)–C(8)
C(14)–C(13)–C(18)
C(14)–C(13)–C(2)
C(18)–C(13)–C(2)
C(15)–C(14)–C(13)
C(16)–C(15)–C(14)
C(15)–C(16)–C(17)
C(18)–C(17)–C(16)
C(17)–C(18)–C(13)
114.45(16)
121.15(17)
115.85(16)
119.64(16)
119.64(16)
60.32(12)
119.97(17)
121.20(17)
118.78(17)
119.42(18)
120.44(19)
120.29(19)
120.03(19)
119.85(18)
116.62(18)
124.17(18)
119.21(16)
Fig. 3. Molecular packing in the crystal of III.
601

Phenyl, lactone, and azlactone cycles are located in one plane (deviation of atoms from the average plane is
ꢉ0.13 Å); cyclopropane ring is at an angle of 69.7ꢂ to this plane. The double bond formed as a result of the condensation
reaction is in cis coplanar position to the double bond of the terpenoid part of the molecule (ꢁ(3)–ꢁ(4)–ꢁ(5)–ꢁ(6) torsion
angle is 7.9(3)ꢂ).
Geometrical parameters of molecules have standard values.
Molecular packing in the crystal (Fig. 3) was determined by the van der Waals interactions.
For the first time we have obtained and characterized (4Z)-{[(1R,6S)-7,7-dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-
en-4-yl]methylene}-2-phenyl-1,3-oxazol-5(4ꢀ)-one III using NMR and single crystal X-ray diffraction analyses.
The work was supported by the Program of Fundamental Research No. 18 of the Presidium of the Russian Academy
of Sciences and by the grant of the President of the Russian Federation for young Russian scientist and Leading Scientific
Schools (NSh-1725.2008.3 and NSh-3019.2008.3).
REFERENCES
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3. F. A. Gimalova, N. K. Selezneva, and M. S. Miftakhov, ibid., 42, No. 8, 1267 (2006).
4. APEX2 Software Package, AXS Inc., 5465, Bruker East Cheryl Parkway, Madison, WI 5317.
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