(z)-solanone, and preparation process and use thereof

Abstract

A (Z)-solanone has the steric formula of: ##STR00001##
or ##STR00002##
with the name of (S,Z)-5-isopropyl-8-methyl-6,8-diene-2-one or (R,Z)-5-isopropyl-8-methyl-6,8-diene-2-one. A process for the preparation of the (Z)-type solanone and the use thereof in flavoring of cigarette shred are further disclosed. The process includes the following steps: (1) reacting isopentanal and methyl vinyl ketone, under the action of a catalyst and a co-catalyst, to give (S)-2-isopropyl-5-carbonylhexanal or (R)-2-isopropyl-5-carbonylhexanal; (2) reacting the (S)-2-isopropyl-5-carbonylhexanal or the (R)-2-isopropyl-5-carbonylhexanal obtained in step (1) with (iodomethyl)triphenylphosphonium iodide, to give (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or (R,Z)-7-iodo-5-isopropyl-6-ene-2-one; and (3) reacting the (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or the (R,Z)-7-iodo-5-isopropyl-6-ene-2-one obtained in step (2) with pinacol isopropenylborate in the presence of a catalyst to give the (Z)-solanone.

Claims

1. A process for a preparation of (Z)-solanone, comprising the following steps: (1) performing a first reaction on isopentanal and methyl vinyl ketone, under an action of a first catalyst and a co-catalyst, to give (S)-2-isopropyl-5-carbonylhexanal or (R)-2-isopropyl-5-carbonylhexanal; (2) performing a second reaction on the (S)-2-isopropyl-5-carbonylhexanal or the (R)-2-isopropyl-5-carbonylhexanal obtained in step (1) and (iodomethyl)triphenylphosphonium iodide, to give (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or (R,Z)-7-iodo-5-isopropyl-6-ene-2-one; (3) performing a third reaction on the (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or the (R,Z)-7-iodo-5-isopropyl-6-ene-2-one obtained in step (2) and pinacol isopropenylborate in a presence of a second catalyst to give the (Z)-solanone, wherein a name of the (Z)-solanone is (S,Z)-5-isopropyl-8-methyl-6,8-diene-2-one or (R,Z)-5-isopropyl-8-methyl-6, 8-diene-2-one; wherein a reaction scheme of the process is shown as follows: ##STR00013##
or ##STR00014## wherein a steric formula of the (Z)-solanone is: ##STR00015##

2. The process according to claim 1, wherein the first catalyst in step (1) is (S)-2-(methoxydiphenylmethyl)pyrrolidine or (R)-2-(methoxydiphenylmethyl)pyrrolidine, and the co-catalyst is ethyl 3,4-dihydroxybenzoate; a molar ratio of the methyl vinyl ketone to the isopentanal is between 1:1.0 and 1:2.0; a molar ratio of the (S)-2-(methoxydiphenylmethyl)pyrrolidine or the (R)-2-(methoxydiphenylmethyl)pyrrolidine to the isopentanal is between 0.1:1.0 and 0.1:2.0; a molar ratio of the ethyl 3,4-dihydroxybenzoate to the isopentanal is between 0.2:1.0 and 0.2:2.0; a reaction temperature of the first reaction is from −10 to 50° C., and a reaction time of the first reaction is from 20 to 30 h.

3. The process according to claim 1, wherein the second reaction in step (2) is performed under a condition of a basic solvent and adding an additive; a solvent of the basic solvent is tetrahydrofuran, a base of the basic solvent is sodium hexamethyldisilylamide, and the additive is hexamethylphosphoric triamide; a molar ratio of the (S)-2-isopropyl-5-carbonylhexanal or the (R)-2-isopropyl-5-carbonylhexanal to the (iodomethyl)triphenylphosphonium iodide is between 1:1.0 and 1:1.5; a molar ratio of the (S)-2-isopropyl-5-carbonylhexanal or the (R)-2-isopropyl-5-carbonylhexanal to the sodium hexamethyldisilylamide is between 1:1.0 and 1:1.5; a molar ratio of the (S)-2-isopropyl-5-carbonylhexanal or the (R)-2-isopropyl-5-carbonylhexanal to the hexamethylphosphoric triamide is between 1:4.0 and 1:5.0; a reaction temperature of the second reaction is from −100° C. to room temperature, and a reaction time of the second reaction is from 2 to 10 h; the room temperature is 40° C.

4. The process according to claim 1, wherein the second catalyst used in step (3) is [1,1′-bis(diphenylphosphino)ferrocene] palladium dichloride.

5. The process according to claim 1, wherein the third reaction in step (3) is performed in a basic solvent; a solvent of the basic solvent is tetrahydrofuran; a base of the basic solvent is sodium hydroxide; a molar ratio of the (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or the (R,Z)-7-iodo-5-isopropyl-6-ene-2-one to the pinacol isopropenylborate is between 1:1.0 and 1:2.0; a mole ratio of the (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or the (R,Z)-7-iodo-5-isopropyl-6-ene-2-one to the sodium hydroxide is between 1:1.5 and 1:2.5; a molar ratio of the second catalyst to the (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or the (R,Z)-7-iodo-5-isopropyl-6-ene-2-one is between 0.05:1.0 and 0.05:2.0; a reaction temperature of the third reaction is from 0 to 100° C., and a reaction time of the third reaction is from 2 to 10 h.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

(1) The invention is further illustrated by the following examples that are intended only for better understanding the invention and but not for limiting the invention.

Example 1: Synthesis of (S)-2-isopropyl-5-carbonylhexanal or (R)-2-isopropyl-5-carbonylhexanal

(2) 73 mg (about 0.4 mmol) of ethyl 3,4-dihydroxybenzoate were placed in a round-bottom flask, and 53.48 mg (0.2 mmol) of (S)-2-(methoxydiphenylmethyl)pyrrolidine, 215 μL (about 2 mmol) of isopentanal and 243 μL (about 3 mmol) of methyl vinyl ketone were added thereto in order. The reaction mixture was stirred at room temperature to dissolve solids for 24 hours.

(3) After the reaction was completed, the residual methyl vinyl ketone was removed by rotary evaporation, and the residual liquid was separated by a column chromatography with petroleum ether:ethyl acetate of 20:1, to produce 230.1 mg of a light yellow liquid, with the yield of 74%. The product was analyzed to be (S)-2-isopropyl-5-carbonylhexanal, i.e.,

(4) ##STR00007##
and the analyses were shown below:

(5) .sup.1H NMR (400 MHz, Chloroform-d) δ 9.59 ((d, J=2.8 Hz, 1H), 2.47 (m, 1H), 2.35 (m, 1H), 2.11 (s, 3H), 2.07-1.99 (m, 2H), 1.85-1.70 (m, 2H), 0.98 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 208.05, 205.28, 57.50, 41.23, 29.97, 28.34, 20.25, 19.44, 19.31. [α] +47.754° (589 nm), (c 0.54 g/100 mL, CHCl.sub.3).

(6) Except for the use of (R)-2-(methoxydiphenylmethyl)pyrrolidine to replace the catalyst, the conditions were not changed. In this case, the yield was also 74%. The product was analysed to be (R)-2-isopropyl-5-carbonylhexanal, i.e.,

(7) ##STR00008##
and the analyses were shown below:

(8) .sup.1H NMR (400 MHz, Chloroform-d) δ 9.59 (d, J=2.8 Hz, 1H), 2.47 (m, 1H), 2.35 (m, 1H), 2.11 (s, 3H), 2.07-1.97 (m, 2H), 1.86-1.69 (m, 2H), 0.98 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 208.04, 205.28, 57.49, 41.23, 29.97, 28.33, 20.24, 19.44, 19.32. [α] −47.128° (589 nm), (c 0.54 g/100 mL, CHCl.sub.3).

Example 2: Synthesis of (S,Z)-7-iodo-5-isopropyl-6-ene-2-one or (R,Z)-7-iodo-5-isopropyl-6-ene-2-one

(9) 1166 mg (about 2.2 mmol) of (iodomethyl)triphenylphosphonium iodide were placed in a reaction flask, and 3 mL of tetrahydrofuran and 1.1 mL of a 2M (about 2.2 mmol) tetrahydrofuran solution of sodium hexamethyldisilylamide were added thereto. The system, after being stirred at room temperature for 15 minutes, became bright red. The system was cooled to −78° C. and added with 1.6 mL (about 9.2 mmol) of hexamethylphosphoric triamide, and finally, 312 mg (about 2 mmol) of a mixed solution of the (S)-2-isopropyl-5-carbonylhexanal obtained in Example 1 in 2 mL of tetrahydrofuran were added thereto. The mixture was stirred at −78° C. for 4 hours.

(10) After the reaction was completed, the system was added with 2 mL of a saturated sodium bicarbonate solution and then filtered with diatomite, and the filtrate was extracted with ethyl acetate three times. The organic phases were combined and dried with anhydrous sodium sulfate and then concentrated, and the residual liquid was subjected to a column chromatography with petroleum ether:ethyl acetate of 30:1, to give 387 mg of a pale yellow liquid, with the yield of 69%. The product was analyzed to be (S,Z)-7-iodo-5-isopropyl-6-ene-2-one, i.e.,

(11) ##STR00009##
and the analyses was below:

(12) .sup.1H NMR (400 MHz, Chloroform-d) δ 6.31 (d, J=7.4 Hz, 1H), 5.86 (dd, J=9.8, 7.4 Hz, 1H), 2.49-2.31 (m, 2H), 2.24 (m, 1H), 2.12 (s, 3H), 1.82 (m, 1H), 1.69 (m, 1H), 1.50 (m, 1H), 0.92 (d, J=6.8 Hz, 3H), 0.88 (d, J=6.9 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 208.83, 143.31, 83.88, 50.03, 41.21, 31.86, 30.13, 25.29, 20.35, 19.23. [α]+ 34.839° (589 nm), (c 0.62 g/100 mL, CHCl.sub.3).

(13) Except for the use of (R)-2-isopropyl-5-carbonylhexanal obtained in Example 1, the conditions were not changed. In this case, 380 mg of a pale yellow liquid were obtained, with the yield of 68%. The product was analysed to be (R,Z)-7-iodo-5-isopropyl-6-ene-2-one, i.e.,

(14) ##STR00010##
and the analyses were below:

(15) .sup.1H NMR (400 MHz, Chloroform-d) δ 6.31 (d, J=7.4 Hz, 1H), 5.86 (dd, J=9.8, 7.4 Hz, 1H), 2.44-2.35 (m, 2H), 2.24 (m, 1H), 2.12 (s, 3H), 1.82 (m, 1H), 1.69 (m, 1H), 1.50 (m, 1H), 0.92 (d, J=6.8 Hz, 3H), 0.88 (d, J=6.9 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 208.83, 143.31, 83.88, 50.03, 41.21, 31.86, 30.13, 25.29, 20.35, 19.23. [α] −34.032° (589 nm), (c 0.62 g/100 mL, CHCl.sub.3).

Example 3: Synthesis of (5S,6Z)-solanone or (5R,6Z)-solanone

(16) 731 mg (about 1 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]palladium dichloride were placed in a reaction tube, and 70 mL of tetrahydrofuran were added thereto. 2802 mg (about 10 mmol) of (S,Z)-7-iodo-5-isopropyl-6-ene-2-one obtained in Example 2 and 2.8 mL (about 15 mmol) of pinacol isopropenylborate were mixed in tetrahydrofuran to obtain 30 mL of a mixed solution, and 30 mL of the mixed solution were added to the above reaction tube. Finally, 10 mL (about 20 mmol) of a 2M sodium hydroxide aqueous solution were added to the above reaction tube and stirred at 60° C. for 5 hours.

(17) After the reaction was completed, the system was added with water and then extracted with diethyl ether three times. The organic phases were combined and dried with anhydrous sodium sulfate and then concentrated to produce a crude product. The crude product was separated by a column chromatography with petroleum ether:ethyl acetate of 30:1, to give 1425 mg of a pale yellow liquid, with the yield of 73%. The product was analyzed to be (5S,6Z)-solanone i.e., (S,Z)-5-isopropyl-8-methyl-6,8-diene-2-ketone, i.e.,

(18) ##STR00011##
The analyses were shown below:

(19) .sup.1H NMR (400 MHz, Chloroform-d) δ 5.97 (d, J=12.0 Hz, 1H), 5.09 (t, J=11.6 Hz, 1H), 4.95-4.81 (m, 3H), 2.45-2.43 (m, 1H), 2.41-2.30 (m, 2H), 2.10 (s, 3H), 1.85 (s, 3H), 1.81-1.77 (m, 1H), 1.6-1.51 (m, 1H), 1.37 (m, 1H), 0.92-0.89 (d, J=6.8 Hz, 3H), 0.89-0.86 (d, J=6.8 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 209.34, 141.83, 133.67, 132.36, 115.43, 42.90, 41.94, 32.48, 29.98, 26.41, 23.53, 20.23, 19.52. [α] +9.355° (589 nm), (c 0.62 g/100 mL, CHCl.sub.3).

(20) Except for the use of (R,Z)-7-iodo-5-isopropyl-6-ene-2-one obtained in Example 2, the conditions were not changed. 1345 mg of a pale yellow liquid were obtained, with the yield of 69%. The product was analysed to be (5R,6Z)-solanone i.e., (R,Z)-5-isopropyl-8-methyl-6,8-diene-2-ketone, i.e.,

(21) ##STR00012##
The analyses were shown below:

(22) .sup.1H NMR (400 MHz, Chloroform-d) δ 5.97 (d, J=12.0 Hz, 1H), 5.09 (t, J=11.6 Hz, 1H), 4.87 (m, 3H), 2.50-2.43 (m, 1H), 2.42-2.32 (m, 2H), 2.11 (s, 3H), 1.85 (s, 3H), 1.82-1.75 (m, 1H), 1.56 (m, 1H), 1.37 (m, 1H), 0.90 (d, J=6.8 Hz, 3H), 0.87 (d, J=6.9 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) δ 209.34, 141.83, 133.67, 132.36, 115.42, 42.90, 41.94, 32.47, 29.97, 26.40, 23.53, 20.23, 19.52. [α] −9.839° (589 nm), (c 0.62 g/100 mL, CHCl.sub.3).

Example 4: Applications of (Z)-solanone in Flavouring of Cigarette Shred

(23) By taking sample cigarette with a brand produced in Yunnan Province as the experimental object, the quantity of added spices was calculated according to the weight of cigarette shred. The two pure (Z)-solanones synthesized according to the invention, (S,Z)-5-isopropyl-8-methyl-6,8-diene-2-ketone (an injection flavoured cigarette, cited as Sample 1) and (R,Z)-5-isopropyl-8-methyl-6,8-diene-2-ketone (an injection flavoured cigarette, cited as Sample 2), were formulated into an ethanol solution having a certain concentration. With a CIJECTOR essence and spice injector, according to the weight percent 0.005% of the spice in the shred, the ethanol solution was uniformly injected into cigarette; at equivalent conditions, ethanol in the same volume was injected to cigarette (cited as Sample 0) as a control. All samples was balanced at 22° C. and in a relative humidity of 60% for 48 hours. According to the tobacco industrial standards “Tobacco Product—Sensory Evaluation Methods” (YC/T415-2011), the three samples were subjected to sensory comparison evaluations, and the evaluation results were shown in the table below:

(24) TABLE-US-00001 Sample No. 0 1 2 Fragrance Fragrance quality 7 7.5 7.5 characteristics Fragrance quantity 6.5 7 7 Permeability 6.5 7 7 Miscellaneous 7 7.5 7.5 flavour Smoke characteristics Concentration 6 6.5 6 Strength 6 6 6 Fineness 6.5 7 7 Cloud formation 6 6.5 6.5 Mouthfeel Stimulation 7.5 7 7.5 characteristics Dryness 7 6.5 7 Cleanness 7 7 7 Sweet 7 7 7.5 Total score 80 82.5 83.5 Note: a 9-score evaluation method

(25) As seen from the sensory evaluation results, as compared to the control sample, due to the addition of (Z)-solanone, the two examples are conferred with remarkable characteristic fragrances of mature tobacco fragrance, dry grass fragrance, fresh and sweet fragrance or the like, which are in good harmony with initial fragrance of tobacco, increased in richness, fineness, and elegancy of tobacco fragrance and smoke plumpness, and remarkably improved in smoothness and fineness of smoke, and they can further cover miscellaneous flavours and improve aftertaste. By comparing the flavouring effects of the two isomer spices, the (S,Z)-solanone primarily has remarkable enhancing effects in quality and plumpness of fragrance and smoke state; the (R,Z)-solanone primarily has remarkable enhancing effects in richness of tobacco fragrance, fineness and elegancy of smoke, and sweetness and comfortability of aftertaste. In general, the two (Z)-solanones have the enhancing effects in the aspects of richness, plumpness and quality of cigarette fragrance, fineness and elegancy of smoke, and miscellaneous flavour reduction. The two isomers generally have similar effects which are slightly different in the emphases, and thus they have very high values in flavouring formulas of cigarette essences and spices.