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

Abstract

New chiral karenowy spirolactone named (3 ^) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one and formula 1 in the drawing

Description

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

C07D 307/94 (2006.01) (22) Filed on: 03/06/2002

New chiral karene spirolactone and the method of its production (73) The right holder of the patent:

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

December 15, 2003 BUP 25/03 (45) The following was announced about the grant of the patent:

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) Plenipotentiary:

J. Halina Winohradnik,

Wroclaw University of Science and Technology,

Bureau of Invention and Patent Protection (57) 1. New chiral karene spirolactone named (3R) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one and formula 1 presented in the drawing.

PL 197 216 B1

Description of the invention

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

This compound has interesting aromatic properties.

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

The method of producing the new (3R) - (-) - spiro [norkar-4-en-3,5'-tetrahydrofuran] -2'-one of the formula 1 shown in the figure is based on the dehydrohalogenation reaction (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 reflux temperature.

According to the method, the reaction of the halogenolactone with 1,8-diazabicyclo [5.4.1] undec-7-ene is carried out for 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 alkaline with a saturated solution of NaHCO3 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 [norkar-4-en-3,5'-tetrahydrofuran] -2'-one is purified by flash chromatography or vacuum on silica gel using an eluting mixture, preferably in the form of: hexane / isopropanol / acetone / ethyl acetate in the proportion of 60: 3: 1: 1.

The new chemical is a diastereoisomeric carnelian spirolactone having a characteristic and sparse odor described as fresh, rhubarb with a cream-coconut note. The new compound is useful in the perfume and food industries.

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

P r z k ł a d I

0.48 g, i.e. 1.76 mmol of (3R, 4R) - (-) - 4-bromo-spiro [norcarate-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, are added. The reaction mixture is refluxed for 18 h under nitrogen atmosphere. After the reaction is complete as checked by thin layer chromatography (TLC) control, the excess 1,8-diazabicyclo [5.4.1] undec-7-ene is removed from the reaction mixture by washing with 1.0 M HCl. The product is extracted with diethyl ether, made basic with saturated NaHCO 3 solution and washed with H 2 O until neutral. Then, after drying the extract with anhydrous MgSO4, the solvent is evaporated on a rotary evaporator. The thus obtained crude reaction mixture was purified by column chromatography eluting with hexane / isopropanol / acetone / ethyl acetate in the proportion of 60: 3: 1: 1. 0.25 g, i.e. 1.30 mmol of pure crystalline product are obtained, which is 74% of theory.

P r z x l a d II

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

The crystalline product obtained according to Examples 1 and 2 has the following physical and spectral properties:

mp 51-56 ^° C, [ ^{0.1] d 26} = -200.38 ° (c = 1.32, CHCl ₃ );

IR (KBr, ^{cm 1} ): 3030w ^, 2940s ^, 2867m ^, 1763s ^, 1461w ^, 1373w ^, 1183s ^{, 909m; 1} H NMR (CDCl3, δ): 0.95 (two m, 2 H at C-1 and C-6), 0.96 and 1.05 (two s, 6 H 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, pseudoquatorial 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);

GB 197 216 B1 ¹³ C NMR (CDCl, 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.