PL197216B1 - New carane chiral spiro lactone and method of its obtaining - Google Patents

Abstract

A new chiral carene spirolactone named (3^ )-(-)-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one and with formula 1 shown in the figure

Description

(12) PATENT DESCRIPTION (19) PL (11) 197216 (13) B1 ( ²¹ ) Application number: ^{354224 51)} ) Int.Cl·

C07D 307/94 (2006.01) (22) Date of filing: 03.06.2002

New chiral carene spirolactone and method of its preparation (73) Patent holder:

Wrocław University of Science and Technology, Wrocław, PL (43) Application announced:

15/12/2003 BUP 25/03 (45) The patent was granted:

31/03/2008 WUP 03/08 (72) Inventor(s):

Stanisław Lochyński,Wrocław,PL Bożena Frąckowiak,Trzebnica,PL Teresa Olejniczak,Smolec,PL Czesław Wawrzeńczyk,Wrocław,PL Anna Nagielska,Warsaw,PL (74) Representative:

J. Halina Winohradnik,

Wrocław University of Science and Technology,

Office for Invention and Patent Protection (57) 1. A new chiral carene spirolactone named (3R)-(-)-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one and having the formula 1 shown in the drawing.

PL 197 216 B1

Description of the invention

The subject of the invention is a new chiral carene spirolactone and a method for its preparation.

This compound has interesting fragrance properties.

The new chiral carene spirolactone named (3R)-(-)-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one, with formula 1 shown in the figure, has a defined, unambiguous spatial structure.

The method for preparing the new (3R)-(-)-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one, of formula 1 shown in the drawing, consists in the dehydrohalogenation reaction of (3R,4R)-(-)-4-bromo-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one or (3R,4R)-(-)-4-iodo-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one with 1,8-diazabicyclo[5.4.1]undec-7-ene in a solvent such as toluene or diethyl ether at its boiling point.

According to the method, the reaction of halogenolactone with 1,8-diazabicyclo[5.4.1]undec-7-ene is carried out for at least 18 hours under a nitrogen atmosphere, and after cooling and removing excess 1,8-diazabicyclo[5.4.1]undec-7-ene from the post-reaction mixture by washing the post-reaction mixture with 1.0 M HCl, the product is extracted with diethyl ether, basified with a saturated NaHCO3 solution and washed with H2O until neutral. Then, after drying the extract with anhydrous MgSO4 and evaporating the solvent on a rotary evaporator, the crude (3R)-(-)-spiro[norcar-4-en-3,5'-tetrahydrofuran]-2'-one is purified by flash or vacuum chromatography on silica gel using the eluting mixture, preferably in the form of: hexane/isopropanol/acetone/ethyl acetate in the proportion 60:3:1:1.

The new chemical compound is a diastereomeric carene spirolactone with a distinctive and rare scent described as fresh, rhubarb-like with a hint of creamy coconut. The new compound is useful in the perfume and food industries.

The method according to the invention is presented in the following embodiments:

E x a m p l e

0.48 g, i.e. 1.76 mmol of (3R ,4R)-(-)-4-bromo-spiro[norkaran-3,5'-tetrahydrofuran]-2'-one is dissolved in 10 ml of absolute toluene, and then 0.46 g (0.45 ml), i.e. 3.0 mmol of 1,8-diazabicyclo[5.4.1]undec-7-ene is added. The reaction mixture is heated at the reflux temperature of the solvent for 18 h under nitrogen atmosphere. After the completion of the reaction, as determined by thin-layer chromatography (TLC), the excess 1,8-diazabicyclo[5.4.1]undec-7-ene is removed from the reaction mixture by washing everything with 1.0 M HCl. The product was extracted with diethyl ether, basified with saturated NaHCO3 solution, and washed with H2O until neutral. After drying the extract over anhydrous MgSO4, the solvent was evaporated on a rotary evaporator. The resulting crude reaction mixture was purified by column chromatography using an eluent of hexane/isopropanol/acetone/ethyl acetate in a 60:3:1:1 ratio. 0.25 g, i.e. 1.30 mmol, of pure crystalline product was obtained, representing 74% of theoretical yield.

Example II

0.37 g, i.e. 1.16 mmol of (3R,4R)-(-)-4-iodo-spiro[norkaran-3,5'-tetrahydrofuran]-2'-one is dissolved in 15 ml of absolute diethyl ether and 0.36 g (0.35 ml), i.e. 2.30 mmol of 1,8-diazabicyclo[5.4.1]undec-7-ene is added. Then the reaction mixture is heated at the boiling temperature of the solvent until complete consumption of the substrate, constantly monitored by thin layer chromatography (TLC). After completion of the reaction, the whole is diluted with 15 ml of diethyl ether and washed with 1M hydrochloric acid solution to remove excess 1,8-diazabicyclo-[5.4.1]-undec-7-ene. The ether phase was dried over anhydrous magnesium sulfate, and the solvent was then removed on a rotary evaporator. 0.23 g of oily crude product was obtained, which was purified using column chromatography. 0.15 g, i.e. 0.78 mmol, of crystalline compound was obtained, representing 67% of theory.

The crystalline product obtained according to Examples I and II has the following physical and spectral properties:

melting point 51-56 ^o C,[o,]d ²⁶ = -200.38° (c=1.32, CHCl ₃ );

IR (KBr, ^{cm 1} ): 3030w ^, 2940s ^, 2867m ^, 1763s ^, 1461w, 1373w ^, 1183s ^, 909m ^{; 1H} NMR (CDCl3, δ): 0.95 (two m, 2H at C-1 and C-6), 0.96 and 1.05 (two s, 6H at C-8 and C-9), 1.70 (dd, J=11.0 and 4.8 Hz, 1H pseudoaxial at C-2), 1.92-2.08 (two m, 2H, pseudoaquatorial at C-2 and one at C-4'), 2.24 (ddd, J=13.0, 8.6 and 4.8 Hz, 1H at C-4'), 2.52 (m, 2H at C-3'), 5.67 (dm, J=9.8 Hz, 1H at C-5), 5.79 (d, J=9.8 Hz, 1H at C-4);

PL 197 216 B1 ¹³ C NMR (CDCis, δ): 14.96 (q, C-9 or C-8); 19.54 (d, C-1), 22.36 (d, C-2), 26.68 (s, C-7), 27.59 (q, C-9 or C-8), 28.65 (t, C-2), 31.24 (t, C-4'), 34.44 (t, C-3'), 84.86 (s, C-3), 127.61 (d, C-5), 133.80 (d, C-4), 176.92 (s, C-2').

Claims (3)

Patent claims 1. A new chiral karene spirolactone named (3R) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one and formula 1 shown in the figure. 2. The method of producing a new karene spirolactone named (3R) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one and formula 1 shown in the figure, characterized by the fact that it consists in dehydrohalogenation reaction of (3R, 4R) - (-) - 4-bromo-spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one or (3R, 4R) - (-) - 4-iodo -spiro [norcar-4-en-3,5'-tetrahydrofuran] -2'-one, with 1,8-diazabicyclo [5.4.1] -undec-7-ene in a solvent such as toluene or diethyl ether at its temperature boiling. 3. The method according to p. 2. The process of claim 2, wherein the reaction of the halogenolactone with 1,8-diazabicyclo [5.4.1] -undec-7-ene is at least 18 hours. under nitrogen atmosphere, and after cooling and removing the excess 1,8-diazabicyclo [5.4.1] -undec-7-ene from the reaction mixture, by washing the reaction mixture with 1.0 M HCl, the product is extracted with diethyl ether and made basic with saturated NaHCO3 solution and washed with H 2 O until neutral. Then, after drying the MgSO4 extract and evaporating the solvent, the crude (3R) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran} -2'-one is purified by column chromatography using flash or vacuum techniques on silica gel using an eluting mixture, preferably: hexane / isopropanol / acetone / ethyl acetate in the ratio 60: 3: 1: 1.