3,4,7-Trimethyl-2-oxo,-1,6-dioxaspiro(4,5)dec-3-ene
United States Patent [191 Demole 1 Apr. 29, 1975 l 5 3,4,7-TRIMETHYL-2-OXO,-1,6-DIOXSA- SPIRO(4,5)DEC-3-ENE [75] lnventor: Edouard P. Demole. Coppet. VD.  
 Switzerland [73] Assignee: Firmenich S.A., Geneva,  
 Switzerland [22] Filed: June 14, 1973 [2]] Appl. No.: 370.049  
 OTHER PUBLlCATlONS Houben-Weyl. Methoden Der Organischen. Chemie..  
 Band Vl/4, [966. pp. l2-l5 relied on.  
 Morton. The Chemistry of Heterocyclic Compounds. McGraw-Hill Book Co., Inc.. N.Y. and London. 1946, p. 149.  
 Primary ExaminerDonald G. Daus Asxismn! E.ranzinerAnne Marie T. Tighe ,Hmrney Agent, or FirmPennie 8L Edmonds [57] ABSTRACT A compound is disclosed to be useful in the flavouring of foodstuffs, feedstuffs. beverages, pharmaceutical preparations and tobacco products. The said compound is equally found to be a useful perfuming ingredient.  
 A process for the preparation of said compound is disclosed.  
 3 Claims, No Drawings 1 3,4,7-TRIMETHYL-2 OXO.-l ,6-DIOXA-SPIRO-l (4,5)-DEC-3-ENE DESCRIPTION OF THE INVENTION The present invention relates to a compound of formula and to a process for its preparation. The said compound is defined as 3,4,7-trimethyl-2-oxo-l,6-dioxaspiro[4.5ldec-3-ene.  
  The invention relates further to flavouring compositions and a process for improving, enhancing or modifying the flavouring properties of foodstuffs, feedstuffs, beverages, pharmaceutical preparations and, more particularly, tobacco products.  
  A further object of the invention is represented by perfuming compositions and a process for improving, enhancing or modifying the odoriferous properties of perfumes and perfumed products.  
 BACKGROUND OF THE INVENTION It is well known that the tobacco used, for example, for the manufacture of cigarettes comprises a mixture of different types, to give the characteristic flavour and aroma desired in the smoke produced. Thus, cigarettes currently manufactured usually contain mixtures of Virginia, Maryland or Kentucky tobacco in combination with oriental or Turkish tobacco.  
  The respective proportions of the various types of tobacco are varied in order to obtain the particular flavour and aroma desired. It is also common practice to employ flavouring substances and humectants as additives to these tobacco mixtures to further enhance the organoleptic properties thereof.  
  Accordingly, it is an object of the present invention to provide a tobacco or tobacco product having added thereto a small but flavour-modifying quantity of a flavour ingredient, the 3,4,7-trimethyl-2-oxo-l ,6-dioxaspiro[4.5]dec-3-ene.  
  Equally, we have surprisingly found that in view of its specific organoleptic properties, the said compound may find a useful industrial application for the aromatisation of a great variety of materials, namely of foodstuffs and beverages. The said compound represents also a useful perfuming ingredient, and, accordingly, it is a further object of the present invention to provide perfuming compositions containing the 3,4,7- trimethyl-Z-oxo-l ,6-dioxa-spiro[4.5 ]dec-3-ene.  
 PREFERRED EMBODIMENTS OF THE INVENTION We have found that by adding to a tobacco base (which may be natural tobacco or a tobacco substitute of natural or synthetic origin) 3,4,7-trimethyI-2-oxol,6-dixa-spiro[4.5]dec-3-ene, there was obtained a flavoured material which possessed a flavour with a mild, herbal and woody character. These properties are particularly developed on smoking. However, it is to be appreciated that definition or characterisation of flavour or aroma in the tobacco art is almost purely sub jective and different smokers may define the same flavour or effect quite differently.  
 3,4.7-Trimethyl-2-oxol ,6-dioxa spiro[4.5 ]dec- 3-ene in its pure form or in admixture with other flavouring ingredients, may be employed in a variety of forms. The chemical nature, solubility and stability determine the form in which the given compound or composition thereof is to be employed. It is preferable, however, to utilize the said compound or composition in the form of solutions thereof.  
  The additive can be added at any step in the course of the treatment of the tobacco but is preferably added after aging, curing and shredding and before the tobacco is formed into cigarettes or other products.  
  A convenient method for flavouring tobacco consists in spraying the tobacco with an alcoholic solution of the compound or flavouring mixture. Combinations of solvents such as alcohol and propylene glycol may also be used.  
  The proportions of the new compounds to be used in said compositions or in accordance with the process of the present invention can vary within wide limits. Said proportions depend particularly on the specific organoleptic effects it is desired to achieve and on the origin of the tobacco products to which the mentioned flavouring ingredients are added.  
  For instance, interesting flavouring effects can be achieved with amounts ranging from I to I000 ppm, preferencially comprised between about l0 and 200 ppm, more particularly between about 10 and 20 ppm, based on the weight of the product flavoured. when the compound of formula I is used for the flavouring of foodstuffs, feedstuffs, beverages or pharmaceutical preparations, analogous proportions may be employed.  
  When the compound of the invention is used as perfuming ingredient its proportions in the perfume compositions or perfumed products to which it is added may equally be comprised in a wide range. Thus, inter esting odoriferous effects may be achieved by amounts of from about I to about 10 percent of the total weight of the composition.  
  In all cases, the ranges given above may be varied, depending upon the specific odoriferous or flavouring effect it is desired to achieve.  
  The 3 ,4,7-trimethyl-2-oxol ,-dioxaspiro[4.5]dec-3-ene is a compound of natural origin. Said compound has been in fact isolated now for the first time from a natural essential oil. The essential oil has been obtained by extraction with a volatile solvent from the aqueous distillate collected by vapour distillation of a Burley tobacco upon previous acidification of the said distillate to ca. pH 4.  
  The isolation procedure mentioned above is particularly complex and uneconomical as the essential oil is obtained with a yield not higher than 0.03 percent, based on the total weight of the tobacco treated. In fact, after the recovery of the essential oil, the isolation process consisted in a preliminary separation by fractional distillation under reduced pressure whereupon the less volatile fractions [B.p. 35C/0.00l Torr] were subjected to several distillations by means of high fractionating power columns.  
  Finally, the isolation of the desired lactone of formula I, has required the use of specific techniques wherein there was employed preparative vapour phase chromatography (pvpc) utilizing stationary phases of contrasted polarity.  
  The 3,4.7-trimethyl-2-oxo-l,6-dioxa-spiro[4.5]dec- 3-ene is merely a minor constituent of the essential oil. Said compound has been detected in a concentration of ca. 0.03 percent. In its pure state this compound possesses an unprecedented original flavouring and per fuming note. It can in fact develop or simply enhance a variety of notes such as mild, herbal and woody notes. These organoleptic characters are particularly suitable for the aromatization of infusions or decoctions such as tea. camomile. lime tea or verbena for example. When the compound of the invention is used as perfuming ingredient, it can develop very interesting notes with a green or floral character. it confers to the products or compositions to which it is added a very natural and fresh nuance and develops rosy or. in some instances, jasmin-like notes.  
  lts power and tenacity are particularly appreciated in the art, particularly in view of the fact that the above described organoleptic characters are stable and perfectly reproducible. These properties belong specifically to the pure compound, whereas on the contrary. the aroma and odour of the natural essential oil varies in accordance with the origin of the tobacco which has been used as base material for the extraction, the extraction methods chosen and the purity of the essential oil recovered.  
  As a consequence, in view of its flavouring and perfuming properties, lactone I possesses a clearly distinct field of application, said application being also wider than that of the natural essential oil.  
  The discovery of 3,4,7-trimethyl-2oxo-1,(a-dioxaspiro [4.5 idec3-ene has been particularly surprising as this compound represents a hitherto unique example of a spirocyclic lactone occuring in tobacco,  
  By means of an original. industrial and economic process, it is now possible to put to the disposal of the perfumers and flavourists a practically pure 3,4,7 trimethyl-Z-oxo-l ,6dioxa-spiro[4.5]dec-3-ene. The difficulties due to the supply and storage of the tobacco material required for the extraction of the essential oil are thus avoided.  
  According to the invention, 3,4,7 trimethyl-2oxol 6-dioxa-spiro(4.5 ]dec-3-ene is prepared by a process rial c1 Br which comprises treating a compound of formula cs on an wherein Y represents a leaving group or a hydrogen atom, with an acidic agent.  
  A suitable leaving group may be represented by a tetrahydropyranyl group. When in formula ll Y represents a hydrogen atom, compound ll defines a diol and the treatment with an acidic agent may thus be effected either directly on said diol, or on a precursor thereof. Suitable precursors include linear or cyclic ketals, such as for instance dimethyl or diethyl ketal, or the corre&#39; sponding ethylenic ketals. However, in this latter case. there is obtained a ketonc intermediate which before cyclisation must be subjected to a reduction in order to yield the desired diol.  
  Suitable acidic agents include a strong mineral or organic acid, such as cg. hydrochloric, sulphuric, phosphoric or p-toluenesulfonic acid. The reaction may be effected on the starting material of formula ll or on a solution thereof in an inert organic solvent such as an aromatic hydrocarbon, benzene, toluene or xylene for instance.  
  The temperature used for carrying out the above reaction can vary within wide limits. Suitable temperatures are comprised between about and about 150C. However. the best yields of the final product were achieved by using temperatures lying in the vicinity of the boiling point of the chosen solvent.  
  The compounds of formula II wherein Y represents a tetrahydropyranyl group can be prepared according to a reaction of the Grignard type between dimethylmaleic anhydride and the alkylmagnesium halide obtained by reacting, for instance, S-chloro-Z-pentoxytetrahydropyrane with magnesium metal.  
  Compounds ll wherein Y represents a hydrogen atom can be prepared in accordance with the method illustrated by the following reaction scheme:  
 R0 OR I r&#39;due tion 1n the hereinabove scheme symbols R. when taken separately. stand for a lower alkyl radical. such as methyl or ethyl. or they may represent, when taken together. a radical of the type(CH2),, wherein n is the integer 2. 3 or 4.  
  The 5-halopentan-2-one. used as starting material in the above described process, is a commercially available compound. lts conversion into the corresponding ketal can be effected by means of the techniques conventional in the art [cf. e.g. Bull. Soc. Chim. France 2568 (1963)].  
  The formation of the alkyl-magnesium halide, the subsequent addition of this latter on dimethylmaleic anhydride and the reduction of the obtained ketone to give the corresponding secondary alcohol may occur according to the usual techniques [cf e.g. L. F. Fieser and M. Fieser, Organic Chemistry. Reinhold Publ. Corp., New York (1956) and H. O. House, Modern Synthetic Reactions&#34;. W7 A. Benjamin. Inc. New York 1965)].  
  Owing to the presence of a methyl substituent in position 7, formula I is deemed to represent a compound which possesses a bicyclic skeleton wherein the said methyl substituent is in position cis or trans relative to the oxygen atom in position 1.  
  These two isomeric forms are illustrated by the following formulae I cis According to the invention, the compound of formula 1 can be used under the form of one ofits pure isomers or. more frequently. for practical and economic reasons, said compound can be used without further separation as directly obtained by the process of the invention.  
  The invention is better illustrated by the following examples, wherein the temperatures are indicated in degrees Centigrade and the abbreviations have the meaning conventional in the art.  
 EXAMPLE 1 3,4,7 -Trimethyl-2-oxo-l,6-dioxy-spiro[4.5ldec-3-ene A solution of 8 g of the residue obtained by the reaction between dimethylmaleic anhydride and the magnesium halide prepared by the reaction between 5- chloro-2-pentoxytetrahydropyrane and metallic magnesium according to the method described in para graph (c in ml ofbenzene was kept at reflux during 1 A hr in the presence of 0.400 g of p-toluene sulfonic acid. The reaction vessel was connected to a water sep arator and the reaction mixture was kept under nitrogen. After cooling. the product was extracted twice with 100 ml ether and the combined organic extrats were washed with a 5 percent solution of sodium bicarbonate (3 X 100 ml) followed by water until neutrality. By evaporating the volatile portions previously dried over anhydrous magnesium sulfate. there was obtained a residue (6.4 g) which upon purification by means of an elution with ether on a column filled up with g of silica gel gave g of the desired product.  
 B.p. 802/0.001 Torr; d 1.077; n 1.4822. 1R 1755, 16801270. 1085. 1060, 975. 945. 910  
  UV 1 k 213 nm (e 10,000). NMR (CCL) 1.11 (3H.d,.l=6 cps); 1.11-2.30(6H,m); l.74(3H,d, J=l cps); 1.88  
 (3H.d,.l=1 cps); 4.00 (1H, broad m) 6 ppm.  
  MS M 196; m/e: 168, 152. 137. 127, 125, 70, 55. 42.  
  The compound used as starting material in the process described above was prepared as follows a. 2.50 g (0.066 M) of sodium boronhydride were slowly added within 45 min. to a solution of 24.0 g (0.20 M) of 5-chloropentan-2-one in 300 ml anhydrous methanol kept under stirring at a temperature of about 5. The reaction mixture was maintained at room temperature during one night whereupon it was concentrated under reduced pression at low temperature and poured into a mixture of hydrochloric acid and ice. The product was then extracted twice with ml of ether and the combined organic extracts were washed with a 5 percent aqueous solution of NaHCO then with water until neutrality. On drying over MgSO and evaporation, the organic extracts gave 17.2 g (yield 70%) of 5-chloro-pentan-2-ol; B.p. 46-8/ 0.001 Torr.  
 trans b. 17.2 g (0.14 M) of the alcohol prepared according to letter (a) have been mixed with 13.0 g (0.155 M) of dihydropyrane at 20. The reaction was exothermic and it was necessary to provide to an external cooling. After 3 /2 hr a small amount of potassium carbonate was added thereto whereupon the mixture was kept under stirring during 15 min., then filtered and distilled. 21.9 g (yield 75.8 70) of 5-chloro-2-pentoxytetrahydropyrane with B.p. 704/0.00l Torr were obtained.  
 IR 990-1130 cm (complex absorption).  
  NMR (CCl l.15(3H.t.J=6 1.15-2.30(1OH,m); 3.104.l0 (5H,m); 4.60 broad 5)?) ppm.  
  c. 8.28 g (40 mM) of 5-ch1oro-2-pentoxy-tetrahydropyrane in 8 ml tetrahydrofurane were added to a suspension of 1.2 g of magnesium metal (495 m-atom gram) previously activated with iodine on a water bath and a few drops of 1.2-dibromoethane. The addition was effected within 45 min. at ca. 55 under vigorous stirring. The reaction mixture was then kept at this tent perature during 2 more hours whereupon after dilution with an equal volume of tetrahydrofurane it was added within 2 hr to a solution of 4.8 g (38 mM) of dimethylmaleic anhydride in 20 ml of dry tetrahydrofurane at a temperature of 5. The mixture was then kept overnight at 20, acidified with 10 percent sulfuric acid. kept under stirring during one hour and finally ex tracted with 2 portions of 100 ml each of ether. After the usual treatments of washing, drying and evaporation at a temperature lower than 100 under reduced pressure (0.001 Torr) there was obtained a residue which was then directly used for the following reaction step.  
 EXAMPLE 2 2 g of a l percent solution of 3.4.74rimethyl-2-oxol 6-dioxa-spiro[4.5]dec-3ene in 95 70 ethanol were sprayed onto 100 g ofa tobacco mixture of the american blendtype. The tobacco thus flavoured was then used for the manufacture oftest&#34; cigarettes the smoke of which was subjected to an organoleptic evaluation by a panel of flavour experts. These latter unanimously declared that the smoke of the test cigarettes presented a typical character with a mild, herbal and woody note; the tobacco note possessed moreover a more plaisant character than that of the smoke of the control&#34; cigarettes the tobacco of which was simply treated with 95 percent ethanol.  
 EXAMPLE 3 A black tea infusion was prepared by brewing 6 g of commercial black tea leaves in l l of boiling water. After a few minutes brewing the infusion was put into clean cups in an amount of ca ml of solution per cup. To some of the thus prepared cups there were added 0.06 ml of a l percent solution of 3,4,7- trimethyl-2-oxo-1,6dioxa-spiro[4.5]dec-3-ene in 90 percent ethanol.  
  The samples thus obtained were tested by a panel of experienced tasters which declared that the beverage containing the flavouring ingredient possessed a herbal note more distinguished than that of the control sam ples which did not contain the said flavouring ingredient.  
 EXAMPLE 4 A base perfume composition was prepared by mixing the following ingredients (parts by weight) Methyl 1-(cis-pent-Z-cn)l) 3-oxo cyclopentylacctate Hl&#39;f r&#34; 5U Cinnamon at l()&#39;/* 4U Levo-Z-l 2-methyl-prop-2- enyl)-4-methyltetrahdropyrane 2t) Neroli higaradc l0 Linalool 8O Linalyl acetate Linalyl formate 2O Levo-citronellol Citronellyl acetate 30 Citroncllyl formate 20 Hydroxycitronellal 20 Phenylethyl alcohol 20 Methylionone 4U Nerolidol 6G Hexylcinnamic aldehyde 5U Benzyl acetate 70 Heliotropin 3O Cinnamic alcohol 50 Ylang 30 l, l dimethyl-2-acetyl&#39;6- ter-butyl indane 20 Oriental sandclwood 20 a-phenyl-cthylacetatc 20 Total 950 in dicthyl phthalate By adding to g of the above base composition 5 g of 3 ,4,7-trimethyl-2-oxol ,6-dioxa-spiro[4.5 ldec- 3ene, there was obtained a novel composition which possesses a very natural floral character.  
 I claim:  
  1. A composition of matter consisting essentially of a compound of formula 2. A composition of matter consisting essentially of cis-3,4,7-Trimethyl-2-oxol ,6-dioxa-spiro[4.5 ]dec- 3-ene.  
  3. A composition of matter consisting essentially of trans-3,4,7-Trimethyl-2-oxol ,6-dioxa-spirol 4.5 ldec- 3-enel