1,4-DIACYLPIPERAZINE FLAVORED SMOKING COMPOSITIONS

Abstract: Smoking compositions which contain a diacylpiperazine additive such as 1,4-(2-methyl-propionly)-2,3,5,6-tetramethylpiperazine (I). The preferred diacylpiperazine additives impart enhanced flavor response and smoothness.

Description: i 1,4-DIACYLPIPERAZINE FLAVORED SMOKING COMPOSITIONS BACKGROUND OF THE INVENTION The incorporation of flavorants in tobacco products is an important development in the tobacco industry due to the lowered aromaticity of the available tobacco and the increased preference of smokers for filter cigarettes and low del very cigarettes. A variety of organic compounds have been developed and proposed for incorporation as flavorants into tobacco products. Illustrative of such tobacco flavorants are those described in United States patents 2,766,150; 3,180,340; 3,580,259; 3,625,224 3,722,516; 3,750,674; 3,782,391; 3,854,485; 3,879,425; 3,881,025 3,884,247; 3,890,981; 3,903,900; 3,914,451; 3,915,175; 3,920,027 3,924,644; 3,937,228; 3,943,943; 3,586,387; and the like. The tobacco flavorants include compounds such as succinic anhydride; dihydroxyacetone; substituted pyri dines: cinnamic derivatives: isovaleric acid; 6-methylhepta-3,5-dien-2-one; 2-butyl-2-butenal ; 1 ,3-cyclohexadiene; alpha-pyrones; substituted butyrolactones; pyrazines and thiazoli dines; and the like. Of interest with respect to the present invention are various tobacco constituents which have been isolated and identified, as reported in Tobacco Science, 20, 43 (1976). Tobacco constituents having organoleptic properties include pyrrol idine derivatives of the following structure: where R is CHO, C0CH 3 or C0CH 2 CH(CH 3 ) 2 . There is continuing research effort directed to the development of novel compounds which exhib properties sui able for application as flavorants in edible and topical preparations and in smoking compos tions. Accordingly, it is an object of this invention to provide novel p perazine derivatives which exhibit flavorant properties. It is a further object of this invention to provide smoking compositions which have incorporated an additive which exhibits flavorant properties under smoking conditions. Other objects and advantages of the present invention shall become apparent from the accompanying description and examples. DESCRIPTION OF THE INVENTION One or more objects of the present invention are accomplished by the provision of a smoking composition comprising an admixture of (1) combustible filler selected from natural tobacco, reconstituted tobacco, non-tobacco substitutes, and mixtures thereof, and (2) between about 0.00001 and 2 weight percent, based on the total weight of filler, of a di cylpiperazine additive corresponding to the formula: where R is hydrogen or an al yl substituent containing betwee about 1-8 carbon atoms, and R 1 is a hydrocarbyl group containin between about 1-1 carbon atoms. R in the diacylpiperazine formula is selected fro substituents which include hydrogen, methyl, ethyl, propyl , 2 methyl propyl , pentyl , 2-ethyl hexyl , and the like. Rl in the diacylpiperazine formula is selected fro substituents which. include methyl, ethyl, 1-propenyl, butyl, 2 ethylhexyl, decyl , cyclohexyl, phenyl , and the like. The Rl substituents can also be oxygen-containing such as 2-methoxyethyl , 4-methoxyphenyl , and the like. For purposes of the present invention, the preferred diacylpiperazi compounds are those in which R-** contains at least two carbon atoms. Such compounds are advantageous in that they are less volatile, and tend to exhibit favorable flavorant properties under smoking conditions. Thus, in another embodiment this invention provides novel diacylpiperazine compounds as per the formula above in which each Rl substituent contains two or more carbon atoms, such as 1 ,4-dipropionyl-2-methylpiperazine and 1,4- di(2-methylpropionyl ) piperazine. In a further embodiment this invention provides diacyl i erazine compounds as per the formula above which contain at least two R substituents, such as 1 ,4-dipropionyl-2,5- dimethyl pi perazi ne . As illustrated in the Examples, diacylpiperazine compounds can be synthesized by the interaction of appropriately selected acyl halide and piperazine reactants to provide compounds in accordance with the formula above. PREPARATION OF TOBACCO COMPOSITIONS This invention further provides a method of preparing a smoking compositions which is adapted to impart flavoring to the mainstream and sidestream smoke under smoking conditions, which method comprises incorporating into natural tobacco, reconstituted tobacco, non-tobacco substitute or mixtures thereof between about 0.00001 and 2 weight percent, based on composition weight, o diacylpiperazine additive corresponding to the formula: where R is hydrogen or an alky! substituent containing betwee about 1-8 carbon atoms, and R-- is a hydrocarbyl group containin between about 1-12 carbon atoms. An invention diacylpiperazine additive can be incorporate into the tobacco in accordance with methods known and used in th art. Preferably the flavorant additive is dissolved in a solven such as water, alcohol or mixtures thereof, and then sprayed o injected into the tobacco or non-tobacco substitute matrix. Suc method ensures an even distribution of the additive throughout th tobacco, and thereby facilitates the production of a more unifor smoking composition. Alternativel , the flavorant additive may b incorporated as part of a concentrated tobacco extract which i applied to a fibrous tobacco web as in the manufacture o reconstituted tobacco. Another suitable procedure is t incorporate the additive in tobacco or non-tobacco substitut filler in a concentration between about 0.005-5 weight percent based on the weight of filler, and then subsequently to blend th treated filler with filler which does not contain additive. The term "non-tobacco substitute" is meant to includ smoking filler materials such as are disclosed in United State Patents 3,529,602; 3,703,177; 3,796,222; 4,019,521; 4,079,742 and references cited therein; incorporated herein by reference. Illustratively, U.S. 3,529,602 describes a burnable sheet which may be used as a tobacco substitute, which sheet contains ingredients which include (1) a film-forming ingredient comprising a pectinaceous material derived from tobacco plant parts and having an acid value in excess of 30 milligrams of potassium hydroxide per gram, and (2) a mineral ingredient comprising an alkali metal salt, an alkaline earth metal salt or clay. U.S. 3,703,177 describes a process for preparing a non-tobacco smoking product from sugar beet pulp, which process involves the acid hydrolysis of the beet pulp to release beet pectins, and at least an al aline earth treatment thereafter to cause crosslinking of the pectins and the formation of a binding agent for the exhausted beet matrix. U.S. 3,796,222 describes a smoking product derived from coffee bean hulls. The hulls are treated with reagents that attack the alkaline earth metal crosslinks causing the release of the coffee pectins. The pectins act as a binding agent and together with the treated hulls may be handled and used similarly to a tobacco product. U.S. 4,019,521 discloses a process for forming a smoking material which involves heating a cellulosic or carbohydrate material at a temperature of 150 β -750 * C in an inert atmosphere for a period of time sufficient to effect a weight loss of at least 60 percent but not more than 90 percent. U.S. 4,079,742 discloses a process for the manufacture of a synthetic smoking product from a cellulosic material, which process involves a pyrolysis step and a basic extraction step to yield a resultant matrix which has a tobacco-like brown color and has improved smoking characteristics. When a present invention diacylpiperazine compound is incorporated into smoking material as an additive, and cigarettes are manufactured from the flavored blend, under smoking conditions the cigarette taste generally has more response and smoothness and increased flavor amplitude in comparison with control cigarettes which do not contain the invention diacylpi erazine additive. As indicated previously, particularly advantageous ar smoking compositions which contain a diacylpiperazine additive a per the formula above in which each R*-* contains at least two carbo atoms. The superior flavorant properties of the preferre compounds are demonstratd in subjective testing by an experience smoking panel in which 1,4-di acetyl -2-methyl p perazine is judged t have an oily, thin and sharp taste when contained as a flavorant i cigarettes under smoking conditions, and 1,4-di (2-methyl propionyl ) 2, 3, 5, 6-tetramethyl piperazine is indicated as having a smoother an milder taste than control cigarettes. The following examples are further illustrative of th present invention. The reactants and other specific ingredient are presented as being typical, and various modifications can b derived in view of the foregoing disclosure within the scope of th invention. EXAMPLE I 1 , 4-Di acetyl -2-methyl pi perazi ne COCH. I COCH 3 To a cooled stirring solution of 5.0 g (0.05 mole) of 2 methyl piperazine and 11.13 g (0.11 mole) of triethylamine in 200 ml of dichloromethane under nitrogen is added a 8.6 g (0.11 mole quantity of acetyl chloride in 50 ml of dichloromethane over period of about an hour. The resulting mixture is stirre overnight at room temperature. Insoluble solid is removed b filtration and the filtrate is washed with saturated aqueous sodiu chloride, and then with 5% aqueous hydrogen chloride and wit saturated aqueous sodium chloride. The dichloromethane solution i \V-?o dried (magnesium sulfate) and the solvent removed to provide 4.75 of a solid. The solid is recrystallized from benzene and then dri over phosphorus pentoxide in vacuo for four hours to yield 2.73 of 1,4-di acetyl -2-methyl piperazine: mp, 116 * -n7.5'C. The produc structure is confirmed by IR and NMR spectroscopic analysis. EXAMPLE II 2-Methyl -1 ,4-di pentanoyl pi perazi ne CO(CH 2 ) 3 CH 3 I CO(CH 2 ) 3 CH 3 To a cooled stirring solution of 5 g (0.05 mole) of 2 methyl piperazine and 13.15 g (0.13 mole) of triethyla ine in 250 ml of dichloromethane under a nitrogen atmosphere is added a 15.68 (0.13 mole) quantity of pentanoyl chloride in 50 ml o dichloromethane over a period of about one hour. The reaction i allowed to stir at room temperature for 3 days. Insoluble solid i removed by filtration and washed with dichloromethane. Th combined filtrates are washed with water and then stirred with 5 ml of water and 10 ml of saturated aqueous sodium bicarbonate for hours. The dichloromethane layer is separated and washed consecutively with saturated aqueous sodium bicarbonate, 10% aqueous hydrogen chloride and saturated aqueous sodium chloride. The dichloromethane solution is dried (magnesium sulfate) and the solvent is removed under reduced pressure to provide 15.18 g of a semi -sol id. Preparative high pressure liquid chromatography [silicic acid, dichloromethane/ethyl acetate (1:1)] of a portion of the se i-solid yields a solid. Bulb to bulb distil ation (ove temperature range 120 * -130 # C, 0.03 mrn/Hg) of this solid affords 2 methyl-1 ,4-dipentanoylpiperaziπe as a clear oil. IR and NM spectroscopic analysis confirm the product's structure. EXAMPLE III 2, 5-Di methyl -1 , 4-di propi oπyl pi perazi ne COCH 2 CH COCH 2 CH 3 To a cooled stirring solution of 5 g (0.044 mole) of 2,5 dimethyl piperaz ne and 11.5 g (0.114 mole) of triethylamine in 15 ml dichloromethane under a nitrogen atmosphere is added a 10.6 (0.114 mole) quantity of propionyl chloride in 50 ml o dichloromethane over a period of about one hour. The reaction i allowed to stir at room temperature for 3 days. Insoluble solid i removed by filtration and washed with dichloromethane. Th combined filtrates are washed with water and then stirred with 5 ml of water and 10 ml of saturated aqueous sodium bicarbonate for hours. The dichloromethane layer is separated and washed consecutively with saturated aqueous sodium bicarbonate, 10 aqueous hydrogen chloride and saturated aqueous sodium chloride. The dichloromethane solution is dried (magnesium sulfate) and the solvent is removed under reduced pressure to leave a solid. The solid is washed with hexane, recrystal 1 i zed from hexane/acetone, and dried in vacuo for 16 hours at 55 * C over phosphorus pentoxide to yield 4.11 g of 2,5-dimethyl-l ,4-dipropionylpiperaziπe: mp, 130"-131 * C, as confirmed by IR and NMR spectroscopic analysis. The use of benzoyl chloride as a reactaπt in the abov procedure provides the corresponding 2, 5-dimethyl -1 , 4 di benzoyl piperazine product. A mixture of benzoyl chloride an propionyl chloride yields a diacylpiperazine product mixtur containing benzoyl -benzoyl , propionyl -propionyl and benzoyl propionyl 1,4-di substituted compounds. EXAMPLE IV 1,4-Di butyryl -2, 5-dimethyl piperazine The reaction of 5 g (0.044 mole) of 2, 5-dimethyl piperazin with 12.15 g (0.0114 mole) of butyryl chloride is conducted a described in Example III, and the crude product obtained is an oil solid. The solid is washed with hexane, recrystallized from hexane/acetone, and dried in vacuo for 16 hours at 55 * C over phosphorus pentoxide to yield 6.47 g of 1 ,4-dibutryl-2,5- dimethyl piperazine: mp, 92 * -94 * C, as confirmed by IR and NMR spectroscopic analysis. The use of ethoxyacetyl chloride as a react ant in the • above procedure provides the corresponding 1,4-di ethoxyacetyl -2, 5- dimethyl piperazine product. EXAMPLE V 2-Ethyl-l ,4-di (2-methyl propionyl )piperazine COCH(CH 3 ) 2 COCH(CH 3 ) A mixture of 7.0 g (0.065 mole) of ethyl yrazine, 0.7 g of 10% palladium on carbon and 100 ml of ethanol are shaken under a hydrogen atmosphere at about 50 psi and room temperature for 2 days. The mixture is filtered and 0.7 g of 10% palladium on charcoal is added. The mixture is shaken under a hydrogen atmosphere at about 50 psi .and room temperature for 2 days. The resultant product mixture is filtered and the ethanol removed under reduced pressure to leave an oil. The oil is distilled under reduced pressure to yield 4.8 g of 2 -ethyl piperazine: mp, 59 * - 60' C. The reaction of 4.7 g (0.041 mole) of 2 -ethyl piperazine with 11.4 g (0.107 mole) of 2-methyl propi onyl chloride is conducted as described in Example III, and an oil is obtained. Bulb to bulb distillation under reduced pressure (0.15 mm/Hg) is carried out on a 2 g portion of the oil. The material collected over the oven temperature range 120"-130 * C solidified on scratching. It was dried in vacuo (0.05 mm/Hg) for 16 hours over phosphorus pentoxide at room temperature, and 5 hours over sodium hydroxide at 50'C to afford 1.3 g of 2 -ethyl -1,4-di (2-methyl propi onyl )piperazine: mp, 70 * -73 * C, as confirmed by IR and NMR spectroscopic analysis. EXAMPLE VI 1 ,4-Di (2-methy ropi onyl )-2,5-dimethylpiperazine To a cooled, stirring solution of 5.7 g (0.05 mole) o 2, 5-dimethyl piperazine in 150 ml of dich oromethane containin 13.15 g (0.13 mole) of triethylamiπe is added a solution of 13.85 (0.13 mole) of 2-methyl propionyl chloride in 50 ml o dichloromethane. The resulting mixture is stirred at roo temperature for 3 days. Insoluble solid is removed by filtratio and washed with dichloromethane. The combined filtrates ar stirred with 50 ml of water and 10 ml of saturated aqueous sodiu carbonate for one hour. The organic layer is washed with a sodiu carbonate solution followed by 10% hydrochloric acid and wate washes. The solution is dried over magnesium sulfate and th solvent is removed under reduced pressure to yield 12.0 g of solid. Recrystallization of the solid from acetone yields 6.6 g o the pure product: mp, 175 * -177 * C. The structure is confirmed b spectroscopic analysis. EXAMPLE VII 1 ,4-Di (2-methyl propionyl )-2,6-dimethylpiperazine COCH(CH ) COCH(CH 3 ) 2 Th e reaction of 5.7 g (0.05 mole) of ' 2,6- dimethyl piperazine with 13.85 g (0.13 mole) of 2-methyl propionyl chloride is carried out as described in Example VI, and yields 13.3 g of crude product as a solid. Recrystallization from acetone provides 7.1 g of the pure product: mp, 160 * -161 * C. An additional 4.0 g of pure product is obtained by concentrating the mother liquor and adding hexane. The assigned product structure is consistent with IR and NMR data. EXAMPLE VIII 1 ,4-Di (2-methyl propi onyl ) -2-methyl piperazine COCH(CH 3 ) 2 COCH(CH 3 ) Using the procedure of Example VI, the interaction of 2- methyl p perazine with 2-methyl propionyl chloride yields a solid product: mp, 120 * -121'C. IR and NMR data confirm the above indicated structure. EXAMPLE IX 1 ,4-Di (2-methyl propi onyl )-2,3,5,6-tetramethylpiperazine I COCH(CH 3 ) 2 Using the procedure of Example VI, the interaction o 2,3,5,6-tetramethylpiperazine with 2-methyl propionyl chlorid yields a solid product: mp, 145 * -158"C. IR and NMR data confir the above indicated structure. EXAMPLE X This Example illustrates the preparation of present invention smoking compositions. Cigarettes are fabricated employing a blend of tobacco treated with an ethanol ic solution of a diacylpiperazine additive to provide a tobacco with a 100-500 ppm concentration of additive. The cigarettes are targeted to deliver 3-16 mg of tar per cigarette. Untreated controls are prepared and the treated cigarettes are compared to the controls by an experienced smoking panel: Add tive Subjective Taste Results vs. Control Ex. I More oily, thin and sharp. COCH. Additive Subjective Taste Results vs. Control Ex. II More response; slight harshness; more taste. 1 CO(CH 2 ) 3 CH 3 Addi ti ve Subjective Taste Results vs . Control Ex. VI COCH(CH-), Less response; tobacco flavor; 3'*2 more smoothness. I COCH(CH 3 ) 2 Add-i tive Subjective Taste Results vs. Control Ex. VII COCH(CH-). More response; more tobacco-like; I J ^ smoother. . COCH(CH 3 ) 2 Additive Subjective Taste Results vs. Control Ex. IX OCH(CH 3 l 2 Smoother and milder. COCH(CH 3 l 2

Claims: CLAIMS 1. A smoking composition comprising an admixture of (1 combustible filler selected from natural tobacco, reconstitute tobacco, non-tobacco substitutes, and mixtures thereof, and (2 between about 0.00001 and 2 weight percent, based on the tota weight of filler, of a diacylpiperazine additive corresponding t the formula: COR .1 ' where R is hydrogen or an alkyl substituent containing betwee about 1-8 carbon atoms, and Rl is a hydrocarbyl group containin between about 1-12 carbon atoms. 2. A smoking composition in accordance with claim 1 wherein the non-tobacco substitutes are selected from pectinaceous, cellulosic and carbohydrate materials. 3. A smoking composition in accordance with claim 1 wherein at least one R substituent in the formula is an alkyl group. 4. A. smoking composition in accordance with claim 1 wherein at least two R substituents in the formula are alkyl groups. 5. A smoking composition in accordance with claim 1 wherein the diacylpiperazine additive is 1 ,4-di acetyl -2- methyl pi perazi ne. 6. A smoking composition in accordance with claim 1 wherein the diacylpiperazine additive is 2-methyl -1 ,4- di pentanoyl piperazine. OMPI 7. A smoking composition in accordance with claim wherein the diacylpiperazine additive is 2,5-dimethyl-l ,4 di propi onyl pi perazi ne . 8. A smoking composition in accordance with claim wherein the diacylpiperazine additive is 1 ,4-dibutyryl-2,5 di methyl pi perazi ne . 9. A smoking composition in accordance with claim wherein the diacylpiperazine additive is 2-ethyl-l ,4-di (2 methyl propionyl )pi perazi ne . 10. A smoking composition in accordance with claim wherein the diacylpiperazine additive is 1 ,4-di (2-methyl propionyl ) 2, 5-dimethyl piperazine. 11. A.smoking composition in accordance with claim wherein the diacylpiperazine additive is 1 ,4-di (2-methyl propi onyl ) 2, 6-di methyl piperazine. 12. A smoking composition in accordance with claim 1 wherein the diacylpiperazine additive is 1 ,4-di (2-methyl propi onyl ) -2-methyl pi perazi ne . 13. A smoking composition in accordance with claim wherein the diacylpiperazine additive is 1 ,4-di (2-methyl propi onyl ) 2, 3, 5,6-tetramethyl pi perazi ne . 14. A smoking composition in accordance with claim 1 wherein the diacylpiperazine additive exhibits flavorant properties under smoking conditions. 15. A method of preparing a smoking composition which is adapted to impart flavoring to the mainstream and sidestream smoke under smoking conditions, which method comprises incorporating into natural tobacco, reconstituted tobacco, non-tobacco substitute or mixtures thereof between about 0.00001 and 2 weight percent, based on composition weight, of diacylpiperazine additive corresponding to the formula: COR where R is hydrogen or an alkyl substituent containing betwee about 1-8 carbon atoms, and R*-- is a hydrocarbyl group containin between about 1-12 carbon atoms. 16. 2-Methyl-l ,4-dipentanoyl piperazine. 17. 2, 5-Dimet yl -1,4-di propionyl piperazine. 18. 1 ,4-Di butyryl -2, 5-dimethyl piperazine. 19. 2-Ethyl-l ,4-di (2-methyl propi onyl ) piperazine. 20. 1 ,4-Di (2-methyl propi onyl )-2,5(dimethylpiperazine. 21. 1 ,4-Di (2-methyl propionyl ) -2, 6-dimethyl piperazine. 22. 1 , 4-Di ( 2-methyl propi onyl ) -2-methyl pi perazi ne . 23. 1 ,4-Di ( 2-methyl propi onyl) -2,3,5, 6-tetramethyl- piperazine. OMPI

Inventors: EDWARDS WILLIAM B III, HOUMINER YORAM, EDWARDS, WILLIAM, B., III, HOUMINER, YORAM
Applicants: PHILIP MORRIS INC, PHILIP MORRIS INCORPORATED
Application year: 1983
Main classification: A24B3
IPC codes: A24B15, C07D295