Vanillin 5-hydroxyesters and smoking compositions containing a vanillin-release additive

This invention provides novel vanillyl 5-hydroxyesters, and smoking compositions which contain a vanillyl 5-hydroxyester as a flavorant-release additive. Under cigarette smoking conditions, a combustible filler and/or paper wrapper additive such as 4'-formyl-2'-methoxyphenyl 5-hydroxy-2-isopropylhexanoate pyrolyzes into vanillin and 2-isopropyl-5-hydroxyhexanoic acid delta lactone flavorants as volatile components of the cigarette smoke.

CROSS-REFERENCE TO RELATED APPLICATIONS 
The subject matter of the present invention is related to that disclosed in 
patent application Ser. Nos. 537,775, filed Jun. 13, 1990; 565,126, filed 
Aug. 10, 1990; 613,013, filed Nov. 15, 1990; 660,881, filed Feb. 26, 1991; 
and 688,436, filed Apr. 22, 1991. 
BACKGROUND OF THE INVENTION 
A variety of flavorants have been developed and proposed for incorporation 
into tobacco products. Illustrative of such tobacco flavorants are those 
described in U.S. Pat. Nos. 3,580,259; 3,625,224; 3,722,516; 3,750,674; 
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; 
3,379,754; 4,036,237; 4,473,085; and the like. 
J. C. Leffingwell et al "Tobacco Flavoring For Smoking Products" (R. J. 
Reynolds publication, 1972) recites a listing of desireable flavorants for 
smoking compositions, which include phenols, terpenols and lactones such 
as guaiacol, 1-undecanol and 5-dodecalactone. 
U.S. Pat. No. 3,251,366 describes tobacco products that contain a lactone 
flavorant additive such as 
.alpha.,.beta.-dimethyl-.gamma.-pentyl-.gamma.-hydroxybutenolide which 
imparts a celery-like note to mainstream smoke. 
U.S. Pat. Nos. 3,372,699 and 3,372,700 describe the use of a lactone such 
as .beta.-methylbutyrolactone or 4-hydroxy-4-methyl-5-hexenoic acid .beta. 
lactone as a flavorant additive in tobacco products. 
U.S. Pat. Nos. 3,380,457; 3,563,248; and 3,861,403 describe other lactones 
which are recommended for use as flavorant additives in tobacco products, 
such as .beta.-methyl-.delta.-valerolactone, 
3-(2-hydroxycyclohexyl)propionic acid .delta. lactone, 
4-methyl-6-n-pentyl-.alpha.-pyrone, and the like. 
The high degree of volatility and ease of sublimation of flavorant 
additives in tobacco products have presented problems in the manufacturing 
operations, and have resulted in a decreased shelf-life of the products 
due to losses of flavorant by evaporation on storage. 
Recent developments have involved incorporating a low volatility organic 
additive to a smoking composition, which under smoking conditions is 
pyrolyzed into one or more fragments that function to improve the taste 
and character of mainstream tobacco smoke, and in some cases a 
consequential improvement of sidestream smoke aroma. 
U.S. Pat. No. 3,312,226 describes smoking tobacco compositions which 
contain an ester additive such as 1-menthyl linalool carbonate. Under 
smoking conditions pyrolysis of the carbonate ester releases menthol which 
flavors the mainstream smoke. 
U.S. Pat. Nos. 3,332,428 and 3,419,543 describe smoking tobacco 
compositions which contain a menthyl carbonate ester of a glycol or 
saccharide, which under smoking conditions decomposes to release free 
menthol into the mainstream smoke. U.S. Pat. No. 3,499,452 discloses 
similar smoking tobacco compositions in which a carbonate ester additive 
releases flavorant volatiles other than menthol. 
U.S. Pat. Nos. 4,119,106; 4,171,702; 4,117,339; and 4,212,310 describe 
other oligomeric and polymeric carbonate ester derivatives which as 
constituents of smoking compositions are stable and non-volatile under 
storage conditions, and are adapted to release pyrolysis products under 
smoking conditions that improve the taste and aroma of the smoke. 
Tobacco Patents, Supplement No. 88/1 (N. & D. J. Foster, Southhampton, 
England) reports a R&D Disclosure by Philip Morris Inc., that describes 
5-hydroxyester compounds such as 2-methoxy-4-methylphenyl 
2-isopropyl-5-hydroxyhexanoate which are utilized as smoking composition 
additives, and which under normal smoking conditions release lactone and 
alcohol flavorants into cigarette smoke. 
Of specific interest with respect to the present invention is the proposed 
utilization of an organic additive to a cigarette paper wrapper to enhance 
sidestream smoke aroma under smoking conditions. U.S. Pat. No. 4,804,002 
describes a tobacco product wrapper containing a flavorant glycoside 
additive comprising an acetal of a carbohydrate and phenolic compound. 
Under cigarette smoking conditions a flavorant additive such as ethyl 
vanillyl-D-glucoside yields ethyl vanillin and levoglucosan as volatile 
pyrolysis products. 
There is continuing research effort to develop low delivery smoking 
compositions which generate mainstream smoke with enhanced taste and 
sidestream smoke with a pleasant aroma under smoking conditions. 
Accordingly, it is an object of this invention to provide smoking 
compositions having incorporated therein a flavorant-release component 
which is characterized by lack of mobility and/or volatility at ambient 
temperature. 
It is another object of this invention to provide cigarette smoking 
products having incorporated therein a flavorant-release additive which 
under normal smoking conditions imparts improved aroma to sidestream 
smoke. 
It is a further object of this invention to provide novel ester compounds 
which are adapted to be incorporated into cigarette filler and/or paper 
wrapper components, and which under normal smoking conditions release 
volatile lactone and vanillin flavorants into cigarette smoke. 
Other objects and advantages of the present invention shall become apparent 
from the following 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 
and tobacco substitutes, and (2) between about 0.000-5 weight percent, 
based on the total weight of filler, of a flavorant-release additive 
corresponding to the formula: 
##STR1## 
where R is hydrogen or a C.sub.1 -C.sub.4 alkyl substituent; and R.sup.1 
is methyl or ethyl. 
In another embodiment this invention provides a cigarette smoking product 
comprising (1) a combustible filler selected from natural tobacco, 
reconstituted tobacco and tobacco substitutes, and (2) a paper wrapper 
which has incorporated therein a flavorant-release additive corresponding 
to the formula: 
##STR2## 
where R is hydrogen or a C.sub.1 -C.sub.4 alkyl substituent; and R.sup.1 
is methyl or ethyl. 
Illustrative of C.sub.1 -C.sub.4 alkyl substituents in the above 
represented flavorant-release additive formula are methyl, ethyl, propyl, 
2-propyl, butyl, 2-butyl and isobutyl groups. 
A cigarette smoking product in accordance with the present invention 
typically contains between about 0.01-5 weight percent of flavorant 
release additive in the paper wrapper. 
In a further embodiment an invention cigarette product contains between 
about 0.01-5 weight percent of flavorant-release additive in the paper 
wrapper, and contains between about 0.0001-5 weight percent of 
flavorant-release additive in the combustible filler, based on the weight 
of filler. 
A present invention flavorant-release additive which is incorporated in 
smoking compositions as described above is a low volatility compound which 
under normal smoking conditions pyrolyzes into two volatile constituents, 
both of which enhance the flavor and aroma of low delivery cigarette 
smoke: 
##STR3## 
where R and R.sup.1 are as previously defined. 
An important feature of an invention smoking composition is the release of 
two flavorants under smoking conditions, one of which is a lactone and the 
other is vanillin or ethyl-vanillin. 
Both the lactone and vanillin volatiles which are released have exceptional 
organoleptic properties. Each of the compounds contributes a pleasant 
flavor and aroma to cigarette smoke. 
Preparation of Flavorant-release Compounds 
The flavorant-release compounds of the present invention are vanillyl 
5-hydroxyesters which can be prepared by a general procedure as 
represented in the following reaction diagram: 
##STR4## 
In the above formulas, R.sup.3 is vanillin acetal or ethyl vanillin 
acetal, and R.sup.4 is a vanillyl or ethyl-vanillyl ester radical after 
removal of the acetal protective functionality. 
In another embodiment this invention provides a novel class of vanillyl 
5-hydroxyesters corresponding to the formula: 
##STR5## 
where R is hydrogen or a C.sub.1 -C.sub.4 alkyl substituent; and R.sup.1 
is methyl or ethyl. 
The novel vanillyl 5-hydroxyesters of the present invention are stable and 
odorless compounds at ambient temperatures. As demonstrated in Example 
VII, the invention vanillyl 5-hydroxyesters decompose at a relatively low 
pyrolysis temperature (e.g., 200.degree. C.) to release a high yield of 
desirable flavor-enhancing lactone and vanillin or ethyl vanillin 
components in cigarette smoke. 
The invention vanillyl 5-hydroxyesters are uniquely adapted to pyrolyze 
into a 100 percent yield of flavor-enhancing components under normal 
smoking conditions. As illustrated in Example VII, in contradistinction a 
closely related compound not in accordance with the present invention, 
i.e., 2'-methoxy-4'-methylphenyl 5-hydroxy-2-isopropylhexanoate, pyrolyzes 
to the extent of about a 16 percent yield of thermolysis products at 
200.degree. C. 
Preparation of Tobacco Compositions 
In a further embodiment the present invention provides a method of 
preparing a smoking composition which is adapted to impart flavor and 
aroma to mainstream and sidestream smoke under smoking conditions, which 
method comprises incorporating into natural tobacco, reconstituted tobacco 
or tobacco substitute between about 0.0001-5 weight percent, based on 
composition weight, of a flavorant-release additive corresponding to the 
formula: 
##STR6## 
where R is hydrogen or a C.sub.1 -C.sub.4 alkyl substituent; and R.sup.1 
is methyl or ethyl. 
The invention, vanillyl 5-hydroxyester flavorant-release additive can be 
incorporated into the tobacco or tobacco substitute in accordance with 
methods known and used in the art. Preferably the flavorant-release 
additive is dissolved in a solvent such as alcohol or aqueous alcohol and 
then sprayed or injected into the tobacco and/or tobacco substitute 
matrix. Such method ensures an even distribution of the flavorant additive 
throughout the filler, and thereby facilitates the production of a more 
uniform smoking composition. Alternatively, the flavorant may be 
incorporated as part of a concentrated tobacco extract which is applied to 
a fibrous tobacco web as in the manufacture of reconstituted tobacco. 
Another suitable procedure is to incorporate the flavorant in tobacco or 
tobacco substitute filler in a concentration between about 0.5-5 weight 
percent, based on the weight of filler, and then subsequently to blend the 
treated filler with filler which does not contain flavorant additive. 
The term "tobacco substitute" is meant to include non-tobacco smoking 
filler materials such as are disclosed in U.S. Pat. Nos. 3,703,177; 
3,796,222; 4,019,521; 4,079,742; and references cited therein, 
incorporated herein by reference. 
U.S. Pat. No. 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 
alkaline earth treatment thereafter to cause crosslinking of the pectins 
and the formation of a binding agent for the exhausted beet matrix. 
U.S. Pat. No. 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. Pat. No. 4,019,521 discloses a process for forming a smoking material 
which involves heating a cellulosic or carbohydrate material at a 
temperature of 150.degree.-750.degree. 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. Pat. No. 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. 
As previously described herein above, an invention flavorant-release 
additive also can be incorporated in the paper wrapper of cigarette 
products for the purpose of enhancing the aroma of cigarette sidestream 
smoke under smoking conditions. 
The following Examples are further illustrative of the present invention. 
The specific ingredients and processing parameters are presented as being 
typical, and various modifications can be derived in view of the foregoing 
disclosure within the scope of the invention.

EXAMPLE I 
The Example illustrates the preparation of reference compound 
2'-methoxy-4'-methylphenyl 5-hydroxy-2-isopropylhexanoate. 
##STR7## 
Procedure A 
A solution of 6.0 g (0.0468 mole) of oxalyl chloride in 4 ml of benzene was 
chilled to 0.degree. C under a nitrogen atmosphere. A solution of 4.0 g 
(0.0234 mole) of 2-isopropyl-5-oxohexanoic acid in 4 ml of benzene was 
added and the solution was warmed to room temperature, and stirred at room 
temperature for 20 hours. Evaporation of the solvent under reduced 
pressure yielded a 2-isopropyl-5-oxohexanoyl chloride residue, and the 
residue was dissolved in 3 ml of benzene. A 3.1 g (0.0222 mole) quantity 
of 2-methoxy-4-methylphenol in 5 ml of benzene was added, and the solution 
was stirred for 20 hours. Ether was added and the solution was washed with 
water, aqueous saturated sodium chloride, and 5% potassium hydroxide. The 
organic layer was dried over anhydrous calcium chloride, and the solvent 
was removed under reduoed pressure to yield a liquid whioh was purified by 
Kugelrohr distillation bp 120.degree.-125.degree. C./0.04 mm Hg. 
A solution of 0.5 g (1.7 mmoles) of the liquid 2'-methoxy-4'-methylphenyl 
2-isopropyl-5-oxohexanoate intermediate in 2-propanol was chilled to 
0.degree. C. Sodium borohydride 16.3 mg (0.4 mmole) was added to the 
solution and stirred at 0.degree. C. for 4 hours. Ether and aqueous 
saturated ammonium chloride were added. The organic layer was washed with 
water and then with aqueous saturated sodium chloride. The organic layer 
was dried over anhydrous magnesium sulfate, and evaporation of the solvent 
under reduced pressure yielded a liquid which was purified by preparative 
thin layer chromatography on silica gel using 15% acetone/hexane as the 
eluent. A 50 mg quantity of the pure product was obtained as an oil. NMR 
and IR spectra confirmed the title compound structure. 
Anal. Calc. for C.sub.17 H.sub.26 O.sub.4 : C, 69.36; H, 8.90 
Found: C, 69.19; H, 9.00 
Procedure B 
2'-methoxy-4'-methylphenyl 2-isopropyl-5-oxohexanoate was prepared in the 
manner described in the above procedure A. 
A 500 mg sample of the keto-ester was added to a mixture of 5 ml of 95% 
ethanol, 50 mg of platinum oxide and 15 mg of sodium nitrite. The 
heterogeneous mixture was charged into a Parr Shaker and hydrogenated at 
45 psi for 24 hours at 25.degree. C. The mixture was filtered, and the 
filtrate was concentrated under reduced pressure, and the residual crude 
product was purified by chromatography on silica gel (20% ethyl acetate in 
hexane) to yield 200 mg (40% yield) of pure product, which was identical 
to that obtained by procedure A. 
EXAMPLE II 
This Example illustrates the preparation of reference compound 
2'-methoxy-4'-propylphenyl 5-hydroxy-2-isopropylhexanoate. 
##STR8## 
Following the steps of procedure B in Example I, the title compound was 
prepared by hydrogenation of 300 mg of 2'-methoxy-4'-allylphenyl 
2-isopropyl-5-oxohexanoate. NMR and IR spectra confirmed the title 
compound structure. 
Anal. Calc. for C.sub.19 H.sub.30 O.sub.4 : C, 70.79; H, 9.38; 
Found: C, 70.5 ; H, 9.6. 
EXAMPLE III 
This Example illustrates the preparation of intermediate compound 
4'-formyl-2'-methoxyphenyl 5-hydroxy-2-isopropylhexanoate propyleneglycol 
acetal. 
##STR9## 
To a cold (0.degree. C.) stirred suspension of 0.20 mole (34.4 g) of 
2-isopropyl-5-oxohexanoic acid in 200 ml of hexane was added dropwise a 
solution of 0.22 mole (28 g) of oxalyl chloride in 200 ml of hexane. The 
reaction mixture was allowed to stand at room temperature for about 18 
hours, then volatile materials were removed on a rotary evaporator. The 
residue was treated with 200 ml of hexane, and removal of the solvent 
provided 34.7 g of liquid acid chloride product. 
A 1-liter 3-neck flask was charged with 10.56 g of sodium hydride (50% in 
mineral oil), and the mineral oil was removed by washing with hexane and 
drying under nitrogen. The resultant dry powder was cooled in an ice bath 
and suspended in ml of tetrahydrofuran. To the suspension was added 
dropwise a solution of 42 g (0.2 mole) of vanillin propyleneglycol acetal 
in 200 ml of tetrahydrofuran. The mixture was stirred at room temperature 
for 2 hours and then cooled in an ice bath and a solution of the above 
prepared acid chloride in 200 ml of tetrahydrofuran was added dropwise. 
The reaction mixture was stirred for about 18 hours at room temperature, 
and then concentrated to one-third its volume on a rotary evaporator and 
diluted with 700 ml water. The organic layer was removed and the aqueous 
layer was extracted with 3.times.200 ml of ether. The combined organic 
layers were washed with 250 ml of 10% sodium carbonate, 250 ml of water, 
and finally with 250 ml of saturated sodium chloride solution. After 
drying over sodium sulfate, the extract was concentrated on a rotary 
evaporator at 50.degree. C. to provide 45.8 g of crude ester product. The 
ester was distilled in a Kugelrohr to yield 25.8 g of keto-ester as a pale 
yellow liquid, bp 125.degree. C./50 mm Hg. 
The keto-ester (25.8 g, 0.07 mole) was dissolved in 200 ml of 95% ethanol 
and the solution was cooled in an ice bath. Solid sodium borohydride (2.7 
g, 0.07 mole) was added in portions over a period of 30 minutes. After 
addition was complete, the reaction medium was stirred for 1 hour at 
0.degree. C., and then quenched by adding 250 ml of saturated ammonium 
chloride solution. The mixture was diluted with 500 ml of water and 
extracted three times with 250 ml of ether. The combined extracts were 
washed with water until neutral, dried over sodium sulfate, and 
concentrated on a rotary evaporator to yield 34 g of a yellow viscous 
liquid. A pure sample of the acetal-protected hydroxyester product was 
obtained by column chromatography on silica gel with elution by 50% ethyl 
acetate/hexane. The structure of the title compound was confirmed by NMR 
and IR spectroscopy. 
EXAMPLE IV 
This Example illustrates the preparation of 4'-formyl-2 -methoxyphenyl 
5-hydroxy-2-isopropylhexanoate in accordance with the present invention. 
##STR10## 
Acetal-protected hydroxy-ester (34 g) prepared in the manner described in 
Example III, was dissolved in 200 ml of acetone and water was added until 
the solution was cloudy, then several drops of dilute hydrochloric acid 
were added. After stirring at room temperature for one hour, the solution 
was concentrated on a rotary evaporator to remove most of the acetone. The 
residue was dissolved in 300 ml of ether, and washed with water and with 
250 ml of saturated sodium chloride solution. The ether solution was dried 
over sodium sulfate, filtered and concentrated on a rotary evaporator to 
yield 26.3 g of crude product. A pure sample was obtained by preparative 
reverse-phase chromatography (55% acetonitrile-water). NMR and IR spectra 
confirmed the title compound structure. 
Anal. Calc for C.sub.17 H.sub.24 O.sub.5 : C, 66.21; H, 7.84; 
Found: C, 65.84; H, 7.96. 
EXAMPLE V 
This Example illustrates the preparation of 4'-formyl-2'-ethoxyphenyl 
5-hydroxy-2-isopropylhexanoate. 
##STR11## 
The synthesis of the title compound was conducted on a 0.1 mole scale 
following the steps described in Example IV, and utilizing an ethyl 
vanillin propylenglycol acetal intermediate. NMR and IR spectra confirmed 
the title compound structure. 
EXAMPLE VI 
This Example illustrates the preparation of 4'-formyl-2'-methoxyphenyl 
5-hydroxy-3-methylhexanoate. 
##STR12## 
The synthesis of the tile compound was conducted on a 0.25 mole scale 
following the steps described in Example IV, and utilizing a 
3-methyl-5-oxohexanoyl chloride intermediate. NMR and IR spectra confirmed 
the title compound structure. 
EXAMPLE VII 
This Example illustrates the thermolysis properties of an invention 
vanillin-release ester compound as compared to reference compounds. 
The thermolysis study was conducted by heating a sample of test compound in 
a sealed tube at 200.degree. C. for 15 minutes. 
______________________________________ 
##STR13## 
Example Number Percent 
Test Compound Thermolysis 
______________________________________ 
IV 100 
III &lt;50 
I 16 
II 9 
______________________________________ 
The summarized data demonstrate that invention compound 
4'-formyl-2'-methoxyphenyl 5-hydroxy-2-isopropylhexanoate (Example IV) 
pyrolyzes cleanly and quantitatively to vanillin and 
2-isopropyl-5-hydroxyhexanoic acid delta lactone products. 
In a further demostration, the Example IV invention compound in an 
ethanbolic solution was applied to the paper wrapper of cigarettes, in a 
quantity of about 800 ppm based on tobacco filler weight. After the 
solvent was removed by drying, the treated cigarettes containing the 
invention additive were evaluated by an experienced smoking panel. 
Compared to untreated control cigarettes, the treated cigarettes exhibited 
a sweet, herbal-spicy, vanillin aroma in the sidestream smoke, without a 
significant change in mainstream smoke flavor. 
The delta lactone product released by pyrolysis of the Example IV compound 
is an identified trace constituent of smoking tobacco, and is known to 
exhibit a complex aroma described as sweet, fruity-floral, spicy-woody and 
herbal green.