US3499452A - Tobacco compositions incorporating novel esters of polyhydroxy compounds - Google Patents

Description

United States Patent O 3,499,452 TOBACCO COMPOSITIONS INCORPORAT- ING NOVEL ESTERS OF POLYHYDROXY COMPOUNDS Andrew G. Kallianos, John F. Porter, and James D. Mold, Durham, N.C., assignors, by mesne assignments, to Liggett & Myers Incorporated, New York, N.Y., a corporation of Delaware No Drawing. Filed June 22, 1967, Ser. No. 649,422 Int. Cl. A24b /04 US. Cl. 13117 6 Claims ABSTRACT OF THE DISCLOSURE This invention relates to esters of polyhydroxy compounds having the following formula:

wherein n is an integer from 1 to 4, R is a radical selected from the group consisting of acyclic alkyls having from 1-12 carbon atoms, vanillin and phenethyl; R is a radical of a polyhydroxy compound selected from the group consisting of monosaccharides, disaccharides, trisaccaharides, polysaccharides and glycols; and X is oxygen. These compounds may be used in applications where release of analcohol by heat is desired. For example, they may be incorporated in tobacco and decompose during smoking of the tobacco thereby releasing a flavorant into the smoke stream. In addition the rate of release of these compounds may be controlled by adjustment of the pH of the medium in which they are dissolved.

DESCRIPTION OF THE INVENTION This invention relates to novel esters of polyhydroxy compounds which may be used a flavorants in tobacco.

The use of flavoring additive in tobacco products has become of increasing importance in the tobacco industry due to the lowered aromaticity of the available tobacco and to the increased preference of some smokers for filter cigarettes. The addition of cetrain desirable flavorants to tobacco is limited by their volatility which causes them to be lost or diminished in quantity during processing and storage of the tobacco product. This problem is even more acute for filter cigarettes containing active adsorbents; such as charcoal, in the filters. During the processing'and storage of this type of product, volatile fiavorants migrate from the tobacco and are irreversibly bound by the active adsorbent, thereby depleting the flavorants in the product and possibly altering the effectiveness of the active adsorbent in its selective removal of undesirable smoke components.

Many of the compounds of this invention possess very desirable aromas when they decompose which permits their incorporation in tobacco asflavorants. These compounds are stable and non-volatile under the conditions of their storage environment and only decompose upon smoking to release the flavorant into the smoke.

Some of the compounds disclosed, particularly those which contain sulfur, release strong disagreeable odors when they decompose. These compounds are particularly useful as fire warning agents.

It is therefore an object of this invention to provide novel esters of polyhydroxy compounds which may be incorporated into a smoking article and which upon smoking will release the flavorant into the smoke.

It is another object of this invention to provide novel 3,499,452 Patented Mar. 10, 1970 "ice esters of polyhydroxy compounds which may be incorporated into tobacco of a smoking article and which will not migrate from the tobacco during processing or storage of the finished article but will release the flavorant into the smoke at a controlled rate during the smoking process.

It is a further object of this invention to provide novel smoking articles containing these carbonate esters.

It is a still further objective of this invention to provide filter cigarettes containing an active adsorbent in the filter and novel esters of polyhydroxy compounds in the tobacco which bind a flavorant in nonvolatile form and release it during the smoking process.

It is still another object of this invention to provide a method for the continuous release of the alcohol from a the carbonate ester by adjustment of the pH of the solution containing the carbonate ester.

-. be employed to react with the polyhydroxy compound 0 [Haj where n is an integer from 1 to 4, R is a radical selected from the group consisting of acyclic alkyls having from 1-12 carbon atoms, vanillin and phenethyl; R is a radical of a polyhydroxy compound selected from the group consisting of monosaccharides, disaccharides, trisaccharides, polysaccharides and glycols; and X is 'a radical selected from the group consisting of oxygen and sulfur.

These compounds may be prepared by reacting the desired alcohol with phosgene to form the corresponding chloroformate. Thechloroformate is then reacted with the polyhydroxy compound inan appropriate solvent such as pyridine to form the desired polyhydroxy compound ester. Generally, I to 4 moles of the chloroformate may thereby forming a mono, di, tri, or tetra polyhydroxy compound derivative. The reaction between the chloroformate' and polyhydroxy compound is generally complete in about 24 hours, with the excess solvent, such as pyridine being removed under vacuum and the product recovered from the reaction medium and dried.

Specific examples of the preparation of various polyhydroxy compound esters are set forthbelow for illustrative purposes.

EXAMPLE 1 DiO-(et hoxycarbonyl) glucose In a reaction flask is placed 41.5 gm. (0.23 mole) of anhydrous D-glucose and 575 ml. of pyridine. After the sugar has dissolved, the flask and contents are cooled in an ice bath. To the cool solution is added 25 gm. (0.23 mole) of ethyl chloroformate over a period of two hours with stirring. The reaction mixture'is allowed to reach room temperature and to stir overnight. The excess pyritwo more times with ZOO-ml. portions of ether. The

combined ether extracts are washed with two ISO-ml. portions of N hydrochloric acid and two -ml. portions of Water. The ether solution is dried over anhydrous sodium sulfate and after filtration, the solvent is removed under vacuum to leave 1.5 gm. of liquid di-O- (ethoxycarbonyl) glucose.

The product, when measured in KBr micropellet, had infrared absorption bands at 1750 and 1250 cmr characteristic of the 0 and C0 stretching vibrations observed for acyclic carbonates of saturated alcohols of this type (J. L. Hales, J. I. Jones and W. Kynaston, J. Chem. Soc., 618 (1957)).

Elemental analysis gave: Percent C, 44.25, 44.21; percent H, 6.23, 6.17. This data is in agreement with an average molecular formula of (C H O C H O Percent C, 44.44; percent H, 6.22.

The ethanol content, determined by vapor phase chromatography following saponification with alcohol NaOH, was found to be' 20.6%. The theoretical ethanol content based on an average formula of (C H O C H O is 27.8%.

EXAMPLE 2 Tri-O-(phenethoxycarbonyl) glucose Into a reaction flask immersed in a Dry Ice-acetone bath at 75 C. is introduced 48.7 gm. (0.49 mole) of liquid phosgene. A sample of 40.0 gm. (0.33 mole) of phenethyl alcohol, dissolved in 25 ml. of n-hexane, is added to the phosgene over a period of one hour, while the solution is being stirred. The reaction flask is then allowed to reach room temperature and the phosgene allowed to reflux for five hours. At the end of this period the excess phosgene, hexane and the hydrogen chloride formed during the reaction is removed under reduced pressure. The crude phenethyl chloroformate is mixed with 100 ml. of ether and the solution washed once with 100 ml. of an aqueous solution containing 11.0 grns. sodium bicarbonate, and twice with 100 ml. portions of water. The organic layer is dried over anhydrous sodium sulfate and the solvent evaporated at reduced pressure yielding 59.5 gm. (99% of the theoretical) phenethyl chloroformate.

Fifty-nine grams (0.32 mole) of the phenethyl chloroformate is added, over a period of one hour, to a solution of 59.6 gm. (0.32 mole) D-glucose in 800 ml. of pyridine cooled in an ice bath. The reaction mixture is allowed to reach room temperature and to stir overnight. The pyridine is removed under vacuum. The residue is mixed with 100 gm. of ice, 100 ml. of concentrated hydrochloric acid and 500 ml. of ether. The ether layer is removed and the aqueous solution is extracted twice more with equal volumes of ether. The combined ether extracts are backwashed in the same manner as set forth in Example 1. Subsequently, the ether is removed under vacuum depositing 35.6 gm. of liquid tri-O-(phenethoxycarbonyl) glucose.

The product, when measured as a smear on NaCl plate, had infrared absorption bands at 1765 and 1265 cm.- characteristic of the C=O and C0 stretching vibrations observed for acylic carbonates of saturated alcohols of this type (J. L. Hales, J. I. Jones and W. Kynaston, J. Chem. Soc., 618 (1957)). Elemental analysis gave: Percent C, 63.32, 63.42; percent H, 6.24, 6.20. This data is in agreement with an average molecular formula of (C H O C H O Percent C, 63.37, percent H, 5.81.

The phenethyl alcohol content, determined by vapor phase chromatography following saponification with alcoholic NaOH, was found to be 50.2%. Pyrolysis at 250 C. yielded 37% phenethyl alcohol. The theoretical phenethyl alcohol content based on an average formula of (C9H902)3'C6H906 is 58.4%.

'EXAMPLE 3 Mono-O-(vanillinoxycarbonyl) glucose Into a reaction flask immersed in a Dry Ice-acetone bath at 75 C. is introduced 150 gm. (1.5 moles) of liquid phosgene and a solution of 94 gm. (0.62 mole) of vanillin in 1.5 liters of methylene chloride. To the mixture is added, with vigorous stirring, 54 gms. (0.68 mole) of pyridine over a period of one hour. The reaction mixture is allowed to reach room temperature and to stand overnight. Subsequently, the excess phosgene, pyridine, and methylene chloride are removed under reduced pressure.

The crude vanillin chloroformate is added, over a period of one hour, to a solution of 110 gm. (0.62 mole) D-glucose in 2.0 liters of pyridine cooled in an ice bath. The reaction mixture is allowed to reach room temperature and to stir overnight. The pyridine is removed under vacuum. The residue is mixed with gm. of ice, 100 ml. of concentrated hydrochloric acid and 500 ml. of ether. The ether layer is removed and the aqueous solution is extracted twice more with equal volumes of ether. The ether extracts are combined and backwashed in the same manner as set forth in Example 1. The ether is evaporated under reduced pressure depositing semicrystalline mono-O-(vanillinoxycarbonyl) glucose. The product is purified by column chromatography using silica gel (containing 6% water) as the adsorbent. The product is eluted with ether. Evaporation of the solvent deposited 15 gm. of purified mono-O-(vanillinoxycarbonyl) glucose.

The product, when measured in methylene chloride solution, had infrared absorption band at 1772 cmf characteristic of the C=O stretching vibration and contiguous bands at 1230, 1206 and 1150 cm.- characteristic of the C0 stretching vibrations observed for phenolic carbonates of this type (J. L. Hales, J. I. Jones and W. Kynaston, J. Chem. Soc., 618 (1957)). Elemental analysis gave: Percent C, 50.79, 50.91; percent H, 4.24, 4.42. This is an agreement with an average molecular formula of (C H OQC H O Percent C, 50.28, percent H, 5.06.

The vanillin content, determined by vapor phase chromatography following saponification with alcoholic NaOH, was found to be 35%. Pyrolysis at 300 C. yielded 38.4% vanillin. The theoretical vanillin content based on an average formula of (C H O )C H O is 42.7%.

EXAMPLE 4 Di-O-[(dodecylthio) carbonyl] glucose Into a reaction flask immersed in a Dry Ice-acetone bath is introduced 18.4 gm. (0.19 mole) of liquid phosgene. While the reaction flask is maintained at -75 C., 25 gm. (0.125 mole of n-dodecanethiol in 25 ml. of cyclopentane is added, dropwise over a period of one hour, with stirring. The reaction mixture is allowed to reach room temperature and remain overnight. The excess phosgene, the cyclopentane, and the HCl formed during the reaction are removed under reduced pressure.

Over a period of 1.5 hours, 16 gm. (0.06 mole) of crude dodecyl thiolchloroformate is added to a solution of 10.8 gm. (0.06 mole) of anhydrous D-glucose dissolved in 245 ml. of pyridine cooled in an ice bath. The reaction mixture is allowed to reach room temperature and to stir for 72 hours. Most of the pyridine is removed under vacuum. The residue is mixed with 30 gm. of ice, 30 ml. of concentrated hydrochloric acid and 100 ml. of ether. The ether layer is removed and the aqueous layer is extracted twice more with 100 ml. volumes of ether. The combined ether extracts are washed successively with 100 ml. of each, 0.1 N hydrochloric acid, 10% solution of sodium bicarbonate, and water. The ether solution is dried over anhydrous sodium sulfate and after filtration, the solvent is removed vacuum leaving a semisolid residue. A portion of this was precipitated from acetone yielding 970 mg. of a white,'fluffy precipitate.

The product, when measured in KBr pellet, had infrared absorption bands at 1700 and 1150 cm.- characteristic of the @O and C-O stretching vibrations and at about 660 cm.- characteristic of the C-S stretching observed for acyclic thiocarbonates formed from saturated alcohols and thiols of this type (R. N. Jones and C. Sandorfy, 1956, Chemical Applications of Spectroscopy. W. West, editor, Interscience Publishers, Inc., New York, pp. 247-580). The elemental analysis gave: percent C, 58.57, 58.30; percent H, 9.31, 9.26; percent S, 10.48, 10.52. This data is consistent with an average molecular formula of (C H SO) .C H O percent C, 60.34; percent H, 9.50; percent S, 10.07.

' Upon pyrolysis at 200 C., 205 mg. of the product yielded 53 mg. of n-dodecanethiol. This is approximately one-half of that expected theoretically from the average molecular formula.

This compound upon decomposition produces a strong disagreeable odor and typifies the use of this type of compound for use as fire warning agents. Obviously, the more disagreeable the odor and the more volatile the material, the more suitable it will be for this purpose. For instance upon decomposition the odor would permeate the surrounding area and give warning of fire to those in the area. The compounds may be incorporated in ceiling paints or in wallboard and would serve as fire warning agents if the substance in which they were impregnated were to he heated beyond the point of decomposition of the fire warning agents.

The amounts of the compounds of this invention which are to be employed as fiavorants for tobacco or as fire warning agents will obviously depend to a great extent upon the nature of the odoriferous material employed and also upon the effect which it is desired to achieve. Obviously, where a very strong odoriferous compound is employed, a lesser amount would have to be used than would be the case where a milder odor is involved. The material in which the compound is to be incorporated also affects the amount of the compound to be employed. For instance in tobacco products the amount to be employed will to a large extent be determined not only by the nature of the compound itself but also by the aroma which is sought, i.e. whether a mild flavor or a strong aromatic one is desired. Generally however, we have found that about 0.001 to 0.5 percent of the polyhydroxy compound ester based on the weight of the tobacco is quite satisfactory.

The polyhydroxy compound esters may be incorporated into the smoking product by any convenient method. Thus the polyhydroxy compound ester may be dissolved in a suitable solvent and applied to the cured cased and blended tobacco by spraying or dipping. The compounds may also be applied to the paper or leaf wrapper by spraying, dipping, brushing or any other method in general use in the industry. Further the compounds may be dissolved or suspended in all or a portion of the cas ing solution and applied to the cured and blended tobacco by spraying or dipping. Still another mode of application may be by incorporating the compounds into homogenized ground tobacco components prior to reconstituting the components into a sheet.

The following examples illustrate the utilization of certain compounds of this invention in tobacco products.

EXAMPLE 5 Approximately 30 mg. of tri-O-(phenetoxycarbonyl) glucose was dissolved in 4 ml. of 95% ethanol. The solution was then applied by spraying with an atomizer to 200 gm. of a commercial blend of cased and cut tobacco in a rotating drum. The ethanol was allowed to evaporate from the tobacco. The treated tobacco was manufactured into cigarettes on a Chico-type cigarette making machine.

EXAMPLE 6 Approximately 14 mgm. of mono-O-(vanillinoxycarbonyl) glucose was dissolved in 10 ml. of 95% ethanol. Aliquots of 10 microliters of the solution were injected uniformly along a path of 55 mm. length in cigarettes manufactured from a commercial blend or specially cased and cut tobacco. The solvent was removed from each cigarette by a gentle stream of air.

Cigarettes prepared as described in the above examples Were evaluated for their smoke characteristics by an experienced taste panel. Cigarettes prepared as described in Example 5 exhibited a light sweet fragrance and flavor and produced a balanced smoke flavor spectrum. The light sweet fragrance and flavor were judged to be characteristic qualities of phenethyl alcohol. Cigarettes prepared as described in Example 6 produced a sweet flavor which was judged to be distinctly vanillin-like.

It is also within the purview of this invention to provide a method for the continuous release of fiavorant alcohols from the carbonate esters by dissolving said esters in buflered solutions. 7

The carbonate esters which may be employed in the method are those esters which have the general formula:

wherein n is an integer from 1 to 4, R" is a radical selected from the group consisting of aliphatic and alicyclic alkyls having from 2 to 10 carbon atoms, vanillin and phenethyl; and R is a polyhydroxy compound selected from the group consisting of monosaccharides, disaccharides, trisaccharides, polysaccharides and glycols.

These compounds may be prepared in the same manner as described above and as described in copending US. application Ser. No. 400,918, assigned to Liggett & Myers Tobacco Company.

The carbonate esters can be decomposed at a rate which is dependent on the temperature and on the pH of the environment thereby releasing fiavorants at a controlled rate. The rate of decomposition increases with increasing pH of the medium in contact with the compounds.

Any buffered system which provides the desired pH may be used. For example an appropriate mixture of disodium phosphate and citric acid may be employed or a bulier system consisting of potassium acid phosphate and disodium phosphate or a system consisting of potassium acid phosphate and sodium hydroxide may be used. Clark and Lubs buffer mixtures described in Lanks Handbook of Chemistry-1946, 6th edition, pp. 1102-1103 have been found to be particularly suitable for use in this aspect of the invention.

The amount of buffer utilized in the process is dependent upon the degree of substitution of the polyhydroxy compound. For instance a tri-substituted derivative consumes three molar equivalents of base whereas a mono-substituted derivative consumes only one molar equivalent.

The controlled release of fiavorant alcohols such as menthol in a buffered solution finds particular utility in room Vaporizers for the sustained release of menthol or other medicinally useful volatile alcohols particularly where it is desired to have the menthol released over a more prolonged period of time than is the case with conventional Vaporizers.

Specific illustrations of the controlled release of flavorant alcohols from carbonate esters may be seen from the following detailed examples.

EXAMPLE 7 An aliquot of 5 m1. of ethanol solution containing approximately 100 mg. of mono-O-(menthoxycarbonyl) glucose was added to a solution composed of 25 ml. of a buffer solution of appropriate pH and 25 ml. of ethanol. The buifers used in this example were Clark and Lubs buffer mixtures described in Langs Handbook of Chemistry-l946, 6th edition, pp. 1102-1103. The reaction flask and contents was immersed in a bath maintained at C. The rate of the release of menthol was determined by measuring the amount of compound remaining TABLE I Pcrcent Mono-O- (Monthoxycarbonyl) Glucose Remaining Time (Hours) pH 7 pH 9 WHOMCDMHOMW EXAMPLE 8 In this example aliquots of tri-O-(phenethoxycarbonyl) glucose were mixed with Clark and Lubs buffers at pH 2 and pH 7 at 80 C. and with Clark and Lubs buffers at pH at 25, 50, and 80 C. In this example, 40 ml. of the appropriate pH buffer and 45 ml. of ethanol were mixed with 2 ml. of an ethanol solution containing 40 mg. of the compound. The rate of decomposition of tri-O- (phenethoxycarbonyl) glucose mixed with the buflers at various pHs are shown in Table 11 below.

The rate of decomposition of tri-O-(phenethoxycarbonyl) glucose in the buffers at different temperatures are 8 shown in Table III below. In this table the pH was maintained constant at a pH of 5.

TABLE III Percent of Tri-O- Time Temp C. (Hours) Having thus provided a written abstract and description of the invention and provided specific examples thereof, it should be understood that no undue restrictions or limitations are to be imposed by reason thereof but that the present inventon is defined by the appended claims.

We claim: I

1. Tobacco smoking articles comprising tobacco and having incorporated in said tobacco a minor proportion of a compound which decomposes upon ignition of said tobacco, said compound having the general formula:

wherein n is an integer from 1 to 4, R is a radical selected from the group consisting of acyclic alkyls having from 1-12 carbon atoms, vanillin and phenethyl; R is a radical of a polyhydroxy compound selected from the group consisting of monosaccharides, disaccharides, trisaccharides, polysaccharides and glycols.

2. Tobacco smoke compositions comprising tobacco and containing a compound having the formula of claim 1 wherein R is a glucosyl radical.

3.'A tobacco smoking article according to claim 1 wherein said compound is di-O-(ethoxycarbonyl) glucose.

4. A tobacco smoking article according to claim 1 wherein said compound is tri-O-(phenethoxycarbonyl) glucose.

5. A tobacco smoking article according to claim 1 wherein said compound is mono-O-(vanillinoxycarbonyl) glucose.

6. Tobacco smoking articles according to claim 1 wherein said compound is added to said tobacco at about 0.001 to about 0.5% by weight based on the weight of said tobacco.

References Cited UNITED STATES PATENTS 2,746,890 5/1956 Legler 1314 3,047,433 7/1962 Bavley et al. 131-17 MELVIN D. REIN, Primary Examiner U.S. Cl. X.R.