Abstract:
4-(1-methoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR1## wherein R 1  represents a hydrogen atom, a hydroxy group or a lower alkoxy group; R 2  and R 3 , which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or, when taken together, R 2  and R 3  represent a methylene dioxy group; useful in flavor and fragrance compositions.

Description:
This application is a continuation-in-part application of and claims priority for U.S. Ser. No. 08/321,976, filed Oct. 12, 1994, now U.S. Pat. No. 5,545,424. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives which are useful as an active ingredient for flavor or fragrance compositions. 
     BACKGROUND OF THE INVENTION 
     Various types of products incorporate ingredients which impart some kind of sensation to the mouth, oral cavity, throat or skin as a flavor or fragrance. Such products include toothpastes, mouthwashes, chewing gums, tobacco products, beverages and pharmaceutical products. 
     For example, 1-menthol and 3-(1-menthoxy)propane-1,2-diol are used as active ingredients in the products described above (e.g., as disclosed in U.S. Pat. No. 4,459,425). These products impart a cooling sensation to the mouth or skin. 
     PCT published application WO 92/10107 discloses that compound (II) represented by the following general formula: ##STR2## wherein R 4  and R 5  are independently --COOR 6  wherein R 6  is H or lower alkyl, provided that in at least one of R 4  and R 5 , R 6  is lower alkyl; wherein Z is a direct bond, or --CH═C(R 7 )--; where R 7  is H or an alkyl group; and Y is a group of the formula (III) or (IV): ##STR3## where R 8  and R 9  are independently H, lower alkyl or --OR 10  where R 10  is H or lower alkyl; is useful as a flavor. 
     However, an ingredient which can impart a more significant and/or stimulating sensation is desired for the consumer market. Moreover, such an ingredient must have good quality and have a long-lasting taste, odor or combination thereof. 
     On the other hand, it has been disclosed that a substituted benzaldehyde acetal compound represented by general formula (V): ##STR4## wherein R 11  is C 1-2  alkyl, R 12  and R 13  are each lower alkyl or R 12  and R 13 , together with oxygen atom to which they bond may form, a cyclic group of the formula --O--R 14  --O-- where R 14  is a lower alkylene or alkylalkylene which may be substituted with a lower alkyl or OH; 
     is useful as a flavor and a fragrance (as disclosed in JP-A-57-188537 and WO 94/06441) (The term &#34;JP-A&#34; as used herein means an &#34;unexamined published Japanese patent application&#34;). 
     However, those compounds do not impart a stimulating sensation or a long-lasting sensation to the mouth or skin. 
     SUMMARY OF THE INVENTION 
     Accordingly, an object of this invention is to provide a new flavor and fragrance compound while meeting the above-described requirements. 
     In view of the above, extensive investigations have been conducted and, as a result, this invention provides 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives with enhanced taste and odor and thus a long-lasting taste and odor is achieved. 
     The present invention provides 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof represented by formula (I): ##STR5## wherein R 1  represents a hydrogen atom, a hydroxy group or a lower alkoxy group, R 2  and R 3 , which may be the same or different, each represents a hydrogen atom, a hydroxy group, a lower alkoxy group, or when taken together, R 2  and R 3  represent a methylene dioxy group. 
     The present invention further provides a flavor or fragrance composition containing the compound of formula (I) or a derivative thereof as an active ingredient. 
     DETAILED DESCRIPTION OF THE INVENTION 
     In formula (I), the lower alkoxy group as represented by R 1 , R 2  and R 3  preferably contains from 1 to 4 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butyloxy group and an isobutyloxy group. 
     More preferably, specific examples include a methoxy group and an ethoxy group. 
     Furthermore, specific examples of the preferred compound of the present invention represented by the formula (I), are compounds shown in Table 1 below, but the compounds of the formula (I) are not limited to these exemplified compounds. 
     In addition, in Table 1, Me, Et, Pr, and n-Bu represents a methyl group, an ethyl group, a propyl group, and an n-butyl group respectively. 
     
                       TABLE 1______________________________________Compound R.sup.1           R.sup.2   R.sup.3                           Name______________________________________1        H      H         H     4-(1-menthoxy-methyl)-                           2-phenyl-1,3-dioxolane-                           (Genzaldehyde-MPD)2        H      OH        OH    4-(1-menthoxy-methyl)-                           2-(3&#39;,4&#39;-                           dihydroxyphenyl)-1,3-                           dioxolane                           (protocatechuic                           aldehyde-MPD)3        H      OME       OH    4-(1-menthoxy-methyl) -                           2-(3&#39;-methoxy-4&#39;-                           hydroxyphenyl)-1,3-                           dioxolane(vanillin-                           MPD)4        H      OEt       OH    4-(1-menthoxy-                           methyl)-2-(3&#39;-ethoxy-                           4&#39;-hydroxyphenyl)-1,3-                           dioxolane(ethyl                           vanillin-MPD)5        OH     OMe       H     4-(1-menthoxy-methyl)-                           2-(2&#39;-hydroxy-3&#39;-                           methoxy-phenyl)-1,3-                           dioxolane(ortho                           vanillin-MPD)6        H      H         OMe   4-(1-menthoxy-methyl)-                           2-(4&#39;-methoxyphenyl)-                           1,3-dioxolane                           (anisaldehyde-MPD)7        H      --O--CH.sub.2                     --O-- 4-(1-menthoxy-methyl)-                           2-(3&#39;,4&#39;-methylenedio                           xyphenyl)-1,3-                           dioxolane(piperonal-                           MPD)______________________________________ 
    
     The abbreviations in Table 1 above are described below: 
     MPD represents an acetal of 3-(1-menthoxy)propanediol. 
     Of these compounds, preferred examples include Compound 2 and Compound 3. 
     4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or derivatives of formula (I) can be produced, for example, using the following Reaction Scheme. ##STR6## 
     That is, 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives of formula (I) can be easily synthesized by reaction of 3-(1-menthoxypropane-1,2-diol (2) with a benzaldehyde derivative (3) in the presence of an acid as a catalyst. 
     Examples of suitable benzaldehyde derivatives (3) include vanillin, protocatechuic aldehyde, ethyl-vanillin, ortho-vanillin, benzaldehyde, anisaldehyde and piperonal (heliotropin). 
     Suitable acids useful as a catalyst include any acid which is typically used in acetalization. Examples of suitable acids include hydrochloric acid, phosphoric acid, sulfuric acid, p-toluene sulfonic acid, acetic acid, anhydrous acetic acid, and propionic acid. 
     The reaction can be conducted in a similar manner to conventional acetalization chemistry. 
     It was found that the 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) obtained enhance taste or odor with a long-lasting taste and odor being produced. 
     Furthermore, it surprisingly turned out that the taste given off by the thus obtained 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) provides new and unexpected flavor characteristics. 
     For example, 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane (Compound 3, vanillin-MPD) of the present invention has a hot, burning and tingling taste with a long-lasting taste. 
     Compound 3 is derived from vanillin and 3-(1-menthoxy)-1,2-propanediol. Vanillin is a common flavor or fragrance ingredient which is very sweet and has a strong vanilla-like odor. 3-(1-Menthoxy)-1,2-propanediol (produced by TAKASAGO INTERNATIONAL CORPORATION, U.S. Pat. No. 4,459,425) is also a flavor or fragrance ingredient which has a menthol-like taste and a cooling effect. 
     That is, the character of Compound 3 of the present invention is different from that of those prior art compounds described above. 
     Compound (I) of the present invention can be used to prolong other sensations such as cooling sensations, for example, in combination with 1-menthol, 3-(1-menthoxy)-1,2-propanediol or isopulegol. When cooling and longer lasting tingling sensations are added together, the result would signal prolonged cooling effects to the user. 
     The burning tingling or bitter sensations are desirable as signals to convey to the user a desired psychological or physiological effect. 
     Compound (I) of the present invention can be used in confectionery, beverages and other foods. More specifically, it can be used in chewing gums, candies, ice creams, ice candies, chocolates, snacks, cookies, cakes, breads, tea, coffee, juice, fruit wine, dairy drinks, carbonated drinks, etc. 
     Also, Compound (I) of the present invention can be used in cosmetic and pharmaceutical products. More specifically, it can be used in mouthwashes, toothpastes, antiperspirant products, deodorant products, colognes, perfumes, lip sticks, soaps, shampoos, hair rinses and detergents, etc. 
     A suitable amount of 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives (I) according to the present invention which is used in a flavor composition or in a fragrance composition to be used in various products, wherein the amount used is from 0.0001 to 30% by weight, preferably from 0.0001 to 10% by weight and more preferably from 0.001 to 0.01% by weight, based on the total weight of the composition. 
     Although many novel synthesized molecules have various effects on the skin, they are often toxic and cannot be applied every day. In contrast, the present invention produces novel compounds that are safe for human skin. 
     The two main moieties, 3-1-menthoxy propane-1,2-diol and an aromatic aldehyde, of the present invention are widely used as flavor and fragrance components. The present compounds are readily hydrolyzed in the stomach, at approximately pH 2 and are therefore, safe for use. 
     The present invention is now illustrated in greater detail with reference to the following synthesis examples, examples and comparative examples. However, these synthesis examples, examples and comparative examples are not to be construed to limit the scope of the invention. 
     The analytical instruments used in the synthesis examples of the present specification were as follows: 
     (1) Nuclear magnetic resonance spectrum ( 1  H-NMR):GSX-500 (500 MHz) (manufactured by JEOL) 
     (2) Mass spectrum (MS):JMS-DX303HF (manufactured by JEOL). 
     Unless otherwise indicated herein, all parts, percentages, ratios and the like are by weight. 
    
    
     SYNTHESIS EXAMPLE 1 
     Synthesis of Vanillin-MPD 
     To a 1.0 liter 2-neck round bottom flask, under a dry nitrogen atmosphere, was added 3,-1-menthoxypropane-1,2-diol (MPD)(17.0 g, 73.9 mmoles), followed by sequential addition of dry toluene (500 ml), vanillin (11.25 g, 73.9 mmoles) and p-toluene sulfonic acid monohydrate (141 mg, 0.74 mmoles). 
     The flask was equipped with a Dean-Stark apparatus filled with 3A molecular sieves. The mixture was refluxed under a dry nitrogen atmosphere for 42 hours at which time the reaction was determined to be complete by chromatographic analysis. 
     After cooling to room temperature (about 20° C.-30° C.), the solvent was removed under reduced pressure to obtain a crude oily residue. Purification of the crude oily residue by flash chromatography (silica gel Si-60, ethyl acetate/hexane=1/5 (by volume)) gave pure vanillin-MPD (17.8 g, 48.9 mmoles, 59.4% of theoretical yield). 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 0.76-0.09 (m, 11 H), 1.25 (m, 1H), 1.35 (m, 1H), 1.62 (m, hZ), 2.1 (m, 1H), 2.2 (m, 1H, 3.1 (m, 1H), 3.3 (m, 1/2H), 3.4 (m, 1/2H), 3.54 (m, 1H), 3.66 (m, 1/2H), 3.75 (m, 1/2H), 3.85 (m, 1/2H), 3.91 (s, 3H), 3.96 (m, 1/2H), 4.08 (m, 1/2H), 4.25 (m, 1/2H), 4.35 (m, 1H), 5.66 (s, 1H), 5.73 (s, 1/2H), 5.8 (s, 1/2H), 6.91 (m, 1H), 6.99 (m, 2H) MS (m/z): 364 (M+). 
     SYNTHESIS EXAMPLES 2 to 7 
     4-(1-Menthoxymethyl)-2-phenyl-1,3-dioxolane or its derivatives as shown in Table 2 below were prepared in the same manner as in Synthesis Example 1 above, except for replacing the substrate, vanillin, with each of the benzaldehyde or its derivatives as shown in Table 2 below. 
     
                       TABLE 2______________________________________                 4-(1-Menthoxy-Synthesis             methyl)-2-phenyl-                              IsolatedExample               1,3-dioxolane or its                              YieldNo.       Substrate   Derivative Produced                              (%)______________________________________2         Protocatechuic                 Protocatechuic                              22.0     aldehyde    aldehyde-MPD3         Ethyl vanillin                 Ethyl vanillin-MPD                              22.04         Ortho vanillin                 Ortho vanillin-MPD                              44.05         Benzaldehyde                 Benzaldehyde-MPD                              63.26         Anisaldehyde                 Anisaldehyde-MPD                              33.57         Piperonal   Piperonal-MPD                              52.2______________________________________ 
    
     Spectral data for each is shown below. 
     Protocatechuic aldehyde-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 5.64 (s, 1/2H, acetal), 5.80 (s, 1/2H, acetal), 6.55 (br s, 2H, --OH) MS (m/z): 350 (M + ) 
     Ethyl vanillin-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 1.44 (t, 3H, --CH 3 ), 4.14 (q, 2H, --OCH 2  --), 5.72 (s, 1/2H, acetal), 5.72 (s, 1H, --OH), 5.83 (s, 1/2H, acetal) MS (m/z): 378 (M + ) 
     Ortho-vanillin-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 3.82 (s, 3H, --OCH 3 ), MS (m/z): 364 (M + ) 
     Benzaldehyde-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 5.80 (s, 1/2H, acetal), 5.93 (s, 1/2H, acetal) MS (m/z): 318 (M + ) 
     Anisaldehyde-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm): 3.82 (s, 3H, --OHC 3 ), 5.76 (s, 1/2H, acetal), 5.88 (s, 1/2H, acetal) MS (m/z): 348 (M + ) 
     Piperonal-MPD 
       1  H-NMR (500 Mhz, CDCl 3 , δ ppm) 5.71 (s, 1/2H, acetal), 5.96 (s, 1/2H, acetal), 5.96 (s, 2H, acetal) MS (m/z): 362 (M + ) 
     Example 1 
     Mouth Sensation of Compounds 
     Odor evaluation and mouth sensation evaluation were carried out on each compound synthesized in the foregoing Synthesis Examples. The results obtained are shown in Table 3 below. 
     
                       TABLE 3______________________________________                        Longevity                               Longevity*    Characteristic               Mouth    of Mouth                               of odor onCompound Odor       Sensation                        Sensation                               blotting paper______________________________________Vanillin-MPD    dilute     hot,     3-4 hours                               &gt;30 days    vanilla/odor               tingling,               burning,               numbingProtocatechuic    medicinal  hot,     3-4 hours                               --aldehyde-MPD        pepper,               burningEthyl    vanilla, sweet               oily,    --     &gt;30 daysvanillin-MPD        metallicOrtho    medicinal, bitter,  --     --vanillin-MPD    vanilla    slightly               hotBenzaldehyde-    sweet, floral               bitter   --     &gt;30 daysMPDAnisaldehyde-    anisyl odor,               slight   10-15  &gt;30 daysMPD      sweet      sweet,   minutes               slippery,               creamyPiperonal-MPD    floral, sweet               bitter   10     &gt;30 days                        minutes______________________________________ *Each compound is soaked into a blotting paper and the longevity of the odor is evaluated. 
    
     Example 2 
     Mouth Sensation Enhancement 
     Compounds of the present invention were tasted pure in small amounts on a wooden toothpick. Thermally hot tea was ingested after a short time. 
     The temperature of tea was determined subjectively by sipping a cup of tea. In the test, a small amount of vanillin-MPD was applied to the mouth via a wooden toothpick before sipping the tea. In the control, no addition treatment was used. 
     The compound of the present invention enhanced the thermally hot sensation to cause the tea to taste hotter in comparison with the tea consumed without the compound of this invention. 
     The results obtained are shown in Table 4 below. 
     
                       TABLE 4______________________________________      Heat Determination        Within 3 min.                   After 30 min.______________________________________Control        hot          warmTest Compound  very hot     hot______________________________________ 
    
     Example 3 
     A 1000 ppm ethanol solution of vanillin-MPD was prepared. Using this stock solution, a series of 5 ml samples of vanillin-MPD diluted with water were prepared at 100 ppm, 10 ppm and 1 ppm concentrations. 
     The procedure used for tasting the samples was as follows. The most dilute sample was tasted first. The sample was gargled for 30 seconds followed by spitting out the solution. Comments were recorded and the next sample was tasted when no effect of the previous sample remained in the mouth. 
     The results obtained are shown in Table 5 below. 
     
                       TABLE 5______________________________________Vanillin-   TimeMPD     2-3 min.  10-15 min. 30 min. 120 min.______________________________________1 ppm   bitter on   sides of   tongue,   slight   tingling,   numbing on   lips10 ppm  very   bitter, hot   sensation   on roof of   mouth and   throat100 ppm very hot  low level  low level                                low level   taste,    hot, sinus hot, sinus                                hot, sinus   bitter    clearing   clearing                                clearing   taste     effect,    effect, effect,             numbing    numbing numbing______________________________________ 
    
     Comparative Example 1 
     Each compound was tasted in the same manner as in Example 3. 
     The results obtained are shown in Table 6 below. In the table, vanillin-PGA represents propylene glycol acetal of vanillin and vanillin-DEA represents diethyl acetal of vanillin. 
     
                       TABLE 6______________________________________Compound  Concentration                 Characteristics______________________________________Vanillin-MPD     neat        hot, bitter, numbing, lasts over                 4 hoursVanillin-PGA     neat        hot bitter taste, lasts only 2-3                 minutesVanillin-DEA     neat        hot bitter taste, lasts only 2-3                 minutesVanillin-DEA     100 ppm     momentary warm, bitter,                 sensation is gone in 30 seconds.______________________________________ 
    
     Vanillin-MPD, vanillin-PGA and vanillin-DEA produce hot sensations at slightly different sites in the mouth. Vanillin-MPD is hotter than vanillin-PGA or -DEA. 
     Example 4 
     Hard Candy 
     A hard candy was prepared using 0.0001 to 10% by weight (1 to 100 ppm) of vanillin-MPD as follows: 
     1 cup of light corn syrup 
     1 cup of water 
     2 cups of sugar 
     1/4 teaspoon of flavoring 
     1/4 teaspoon of food coloring 
     0.0001 or 0.1% by weight of vanillin-MPD 
     The corn syrup, water and sugar were combined in a 2-quart saucepan. The mixture was heated to 300° F. (150° C.) and then removed from the heat. The flavoring, food coloring and vanillin-MPD were then added to the mixture, stirred until blended, poured free-form or into molds and cooled to room temperature to produce a hard candy. 
     The hard candy thus obtained was tasted and evaluated. The results obtained are shown in Table 7 below. 
     
                       TABLE 7______________________________________Vanillin-   TimeMPD     2-3 min.  10-15 min. 30 min.  90 min.______________________________________1 ppm   slight hot             slight hot   taste,    taste,   prickly,  prickly,   numbing   numbing100 ppm hot taste,             hot taste, hot taste,                                 hot   prickly,  prickly,   prickly, taste,   numbing   numbing,   numbing, prickly,             warming    warming  numbing             sensation  sensation             spread down                        spread down             to throat  to throat______________________________________ 
    
     At 100 ppm, vanillin-MPD has a hot taste with a prickly, numbing effect that is mainly on the tongue. It lasts on the tongue for over 90 minutes. This effect spreads throughout the oral cavity. As a result, there is a warming sensation that spreads to the back of the mouth and down the throat. This warming sensation does not last as long as the hot taste, prickly, numbing effects on the tongue. 
     While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof. 
     Example 5 
     Fragrance Composition 
     A fragrance composition (A) or (B) having the following formulation is prepared. 
     
         ______________________________________Formulation         Parts Per 100______________________________________Formulation of fragance composition (A):Gardenia oil        45Vanillin-MPD        15rosewood oil        15rose oil            25Formulation of fragrance composition (B)Dodecahydro-3a,6,6,9a-tetramethyl-               10naphtho 2,1-b!furanArmoise oil         1Basil oil           1Ciste labdanum sis abs               1Citronellol         5Cresyl acetate      0.52,6,6-trimethyl-trans-1-crotonyl-               5cyclohexene-1Eugenol             1Galbanum oil 10%    1Methyl dihydrojasmonate               252-acetyl-1,2,3,4,6,7,8-octahydro-               202,3,8,8-tetramethylnaphthaleneLemon oil           510-oxahexadecanolide               7Methyl-2,2,3-cyclopenten-3-yl-1)-5-               10pentanol-2p-isobutyl-α-methyl-               5dihydrocinnamaldehydeVanillin-MPD        5Ylang oil extra     1______________________________________ 
    
     Vanillin-MPD is preferably formulated into a fragrance composition in an amount of from 0.1% to 30% by weight based on the total weight of the composition. 
     The fragrance composition comprising 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane or a derivative thereof according to the present invention, can further be incorporated into a product, such as a product containing alcohol, preferably in an amount of from 10% to 30% by weight, or in an air freshener product in the form of a solid, a powder, an incense, a gel, a cream, a spray or a liquid, preferably in an amount of from 25% to 55% by weight based on the total weight of the product. 
     Example 6 
     Cream 
     A cream having the following formulation is prepared. 
     
         ______________________________________Cream formulation      Parts______________________________________Polypropylene stearyl ether (arlamol E)                  20Vanillin-MPD           5.0Stearyl alcohol        4.0Steareth 2 (brij 72)   3.4Steareth 21 (brij 721) 1.64Methyl paraben         0.02Water                  65.84______________________________________ 
    
     Vanillin-MPD is preferably formulated into a cosmetic product, such as a cream, in an amount of from 0.005% to 5% by weight, based on the total weight of the product. 
     Comparative Example 2 
     Cream 
     A cream is prepared in the same manner as in Example 6, except that Vanillin is used in place of Vanillin-MPD. 
     EVALUATION EXAMPLE 1 
     Stability of Cream 
     
         ______________________________________   Color         OdorCream     Initial After 1 week                         Initial                               After 1 week______________________________________vanillin  White   Tan, off white                         vanilla                               sour note(Comp. Ex. 2)                 notevanillin-MPD     White   White       vanilla                               vanilla(Ex. 6)                       note  note______________________________________ 
    
     The enhanced stability of vanillin-MPD to discoloration is illustrated by the above example. Vanillin and vanillin-MPD were added to a standard lotion cream base (both at 5%). After one week at room temperature, the vanillin lotion had discolored to an off-white tan color, while the vanillin-MPD lotion remained unchanged. 
     EVALUATION EXAMPLE 2 
     Odor of Cream 
     
         ______________________________________Cream          After 1.5 hour                        After 3 hours______________________________________vanillin       vanilla odor  no odor(Comp. Ex. 2)vanillin-MPD   vanilla odor  vanilla odor(Ex. 6)______________________________________ 
    
     Each cream was respectively applied to the back of the hand. The vanillin cream had an immediate off vanilla odor that lasted 1.5 hours. The vanillin-MPD cream had a slight initial vanilla odor, which increased and lasted for 3 hours.