Abstract:
4-(1-menthoxymethyl)-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 compositions.

Description:
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;-dihydroxy-                          phenyl)-1,3-dioxolane                          (protocatechuic alde-                          hyde-MPD)3       H      OME       OH    4-(1-menthoxy-methyl)-                          2-(3&#39;-methoxy-4&#39;-hy-                          droxyphenyl)-1,3-di-                          oxolane (vanillin-MPD)4       H      OEt       OH    4-(1-menthoxy-methyl)-                          2-(3&#39;-ethoxy-4&#39;-hydroxy-                          phenyl)-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 (anisal-                          dehyde-MPD)7       H      --O--CH.sub.2                    --O-- 4-(1-menthoxy-methyl)-                          2-(3&#39;,4&#39;-methylenedioxy-                          phenyl)-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 its 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)-1,2propanediol (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 is from 0.0001 to 10% by weight and preferably from 0.001 to 0.01% by weight based on the total weight of the composition. 
     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______________________________________Synthesis          4-(1-Menthoxymethyl-2-                               IsolatedExample            phenyl-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     Characteristic           of MouthCompound  Odor       Mouth Sensation                              Sensation______________________________________Vanillin-MPD     slight vanilla                hot, tingling, burn-                              3-4 hours                ing, numbingProtocatechuic     --         hot, pepper, burning                              3-4 hoursaldehyde-MPDEthyl     --         oily, metallic                              --vanillin-MPDOrtho     --         bitter, slightly hot                              --vanillin-MPDBenzaldehyde-     --         bitter        --MPDAnisaldehyde-     anisyl odor                slight sweet, 10-15MPD                  slippery, creamy                              minutesPiperonal-MPD     slight floral                bitter        10 minutes     odor______________________________________ 
    
     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______________________________________   TimeVanillin-MPD     2-3 min.  10-15 min.                         30 min.                                120 min.______________________________________ 1 ppm    bitter on     sides of     tongue,     slight     tingling,     numbing on     lips 10 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______________________________________   TimeVanillin-MPD     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 taste,     prickly,  prickly,  prickly,                                prickly,     numbing   numbing,  numbing,                                numbing               warming   warming               sensation sensation               spread    spread               down to   down to               throat    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.