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Title:
PROCESS FOR PREPARING BETA-KETOESTER FRAGRANCE PRO-ACCORDS FROM 1,3-DIOXAN-4,6-DIONES
Document Type and Number:
WIPO Patent Application WO/1999/016740
Kind Code:
A1
Abstract:
The present invention relates to methods for preparing $g(b)-ketoester fragrance pro-accords from activated acyl units, 1,3-dioxan-4,6-diones and fragrance raw material alcohols. The first step of the disclosed process involves contacting an activated acyl unit, preferably an acid chloride, with a 1,3-dioxan-4,6-dione, an example of which is Meldrum's acid, to form a 2-acyl 1,3-dioxan-4,6-dione which is then reacted with a fragrance raw material alcohol to form the final $g(b)-ketoester fragrance pro-accord. The resulting $g(b)-ketoester fragrance pro-accords are suitable for use in laundry detergent, personal care, and other formulations wherein aesthetic fragrance materials are employed.

Inventors:
Ortiz, Rafael (890 Windrow Lane Milford, OH, 45150, US)
Schechtman, Lee Arnold (2069 Edinburg Lane Fairfield, OH, 45014, US)
Sivik, Mark Robert (2434 Sheffield Court Ft. Mitchell, KY, 41017, US)
Wos, John August (8505 Harperpoint Drive Cincinnati, OH, 45249, US)
Application Number:
PCT/IB1998/001340
Publication Date:
April 08, 1999
Filing Date:
August 28, 1998
Export Citation:
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Assignee:
THE PROCTER & GAMBLE COMPANY (One Procter & Gamble Plaza Cincinnati, OH, 45202, US)
Ortiz, Rafael (890 Windrow Lane Milford, OH, 45150, US)
Schechtman, Lee Arnold (2069 Edinburg Lane Fairfield, OH, 45014, US)
Sivik, Mark Robert (2434 Sheffield Court Ft. Mitchell, KY, 41017, US)
Wos, John August (8505 Harperpoint Drive Cincinnati, OH, 45249, US)
International Classes:
C07D319/06; A61K8/00; A61K8/35; A61K8/37; A61Q5/02; A61Q13/00; A61Q19/10; C07C67/32; C07C69/738; C11D3/20; C11D3/50; (IPC1-7): C07C69/738; C07C67/32; C07D319/06
Domestic Patent References:
WO1998007405A1
Other References:
P.HOUGHTON ET AL.: "Modified Preparation of beta-Keto Esters" SYNTHESIS., no. 6, June 1982, pages 451-452, XP002084144 STUTTGART DE cited in the application
YUJI OIKAWA ET AL.: "Meldrum's Acid in Organic Chemistry.2.A General and Versatile Synthesis of beta-Keto Esters" JOURNAL OF ORGANIC CHEMISTRY., vol. 43, no. 10, 12 May 1978, pages 2087-2088, XP002084145 EASTON US cited in the application
Attorney, Agent or Firm:
Reed, David T. (The Procter & Gamble Company 5299 Spring Grove Avenue Cincinnati, OH, 45217, US)
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Claims:
WHAT IS CLAIMED IS:
1. A process for preparing a pketoester fragrance proaccord comprising the steps of : a) reacting in the presence of a base a having the formula: wherein R1 and R2 are each independently ClClo alkyl, C2Clo alkenyl, C7C22 alkylenearyl, C6Clo aryl, and mixtures thereof ; with an activated acyl group having the formula: wherein R3, R4, and R5 are each independently hydrogen, ClC30 substituted or unsubstituted linear alkyl, C3C30 substituted or unsubstituted branched alkyl, C3C30 substituted or unsubstituted cyclic alkyl, C 1C30 substituted or unsubstituted linear alkoxy, C3C30 substituted or unsubstituted branched alkoxy, C3C30 substituted or unsubstituted cyclic alkoxy, C2C30 substituted or unsubstituted linear alkenyl, C3C30 substituted or unsubstituted branched alkenyl, C3C30 substituted or unsubstituted cyclic alkenyl, C2C30 substituted or unsubstituted linear alkynyl, C3C30 substituted or unsubstituted branched alkynyl, C6C30 substituted or unsubstituted alkylenearyl; or R3, R4, and R5 can be taken together to form C6C30 substituted or unsubstituted aryl; and mixtures thereof ; X is an acyl activating unit; to form an acyl 1,3dioxane4,6dione, the enol tautomer of which having the formula: b) optionally, isolating said acyl 1, 3dioxane4,6dione; and c) reacting said acyl 1,3dioxane4,6dione from step (a) or (b) with a fragrance raw material alcohol having the formula: ROH to form a (3ketoester fragrance proaccord having the formula: wherein R3, R4, and R5 are the same as defined herein above.
2. A process according to Claim I wherein step (a) is performed in the presence of a solvent.
3. A process according to either Claim 1 or 2 wherein said solvent is selected from the group consisting of dichloromethane, 1,2dichloroethane, 1,2,3trichloroethane, pentane, hexane, tetrahydrofuran, diethyl ether, benzene, toluene, xylene, 1,4 dioxane, acetonitrile, N, Ndimethylformamide, dimethyl sulfoxide, hexamethyl phosphoramide and mixtures thereof.
4. A process according to any of Claims 13 wherein step (a) is performed at a temperature of form70° C to 100° C.
5. A process according to any of Claims 14 wherein said base is selected from the group consisting of alkylamines, aromatic amines, polymeric amines, organo lithium compounds, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonate, alkali metal hydrides, alkaline earth metal hydrides, and mixtures thereof.
6. A process according to any of Claims 15 wherein said fragrance raw material alcohol ROH is selected from the group consisting of linalool, dihydromyrcenol, menthol, and mixtures thereof.
7. A process according to any of Claims 16 wherein step (c) is performed in the presence of a solvent, said solvent is selected from the group consisting of dichloromethane, 1,2dichloroethane, 1,2,3trichloroethane, pentane, hexane, tetrahydrofuran, diethyl ether, benzene, toluene, xylene, 1,4dioxane, acetonitrile, N, Ndimethylformamide, dimethyl sulfoxide, hexamethyl phosphoramide and mixtures thereof.
8. A process according to any of Claims 17 wherein step (c) further comprises an acid catalyst.
9. A process for preparing a Pketoester fragrance proaccord comprising the steps of : a) reacting in the presence of a base having the formula: with an acyl halide having the formula: R3, R4 and R5 are each independently hydrogen, C 1C 16 substituted or unsubstituted linear alkyl, C3C 16 substituted or unsubstituted branched alkyl, or R3, R4, and R5 are taken together to form C6C30 substituted or unsubstituted phenyl, naphthyl, and mixtures thereof ; X is selected from the group consisting of chlorine, bromine, iodine, and mixtures thereof ; to form an acyl the enol tautomer of which having the formula: b) optionally, isolating said acyl 6dione; and c) reacting said acyl 6dione from step (a) or (b) with a fragrance raw material alcohol having the formula: ROH to form a bketoester fragrance proaccord having the formula: wherein R is selected from the group consisting of 3, 7dimethyl1,6octadien 3yl, 2,6dimethyl7octen2yl, (a, a4trimethyl3cyclohexenyl) methyl, cis 3hexen1yl, 9decen1yl, 2,6dimethyl3, 5octadien2yl, 3,7dimethyl6 octen1yl, and mixtures thereof ; R3, R4, and R5 are the same as defined herein above.
10. A process for preparing propionate comprising the steps of : a) reacting in the presence of a base 6dione having the formula: with bnaphthoyl chloride to form 5bnaphthoyl2,2dimethyl1,3dioxane 4,6dione, the enol tautomer of which having the formula: b) optionally, isolating said 5bnaphthoyl2, 2dimethyl1,3dioxane4,6dione; and c) reacting 5bnaphthoyl2,2dimethyl1,3dioxane4,6dione from step (a) or (b) with linalool to form 3 (bnaphthyl)3 oxopropionate having the formula:.
Description:
PROCESS FOR PREPARING BETA-KETOESTER FRAGRANCE PRO-ACCORDS FROM 1,3-DIOXAN-4,6-DIONES FIELD OF THE INVENTION The present invention relates to methods for preparing (3-ketoester fragrance pro-accords, said pro-accords useful for providing sustained fragrance to items which deliver perfume for aesthetic reasons inter alia laundry detergent compositions, fabric softeners, personal care and personal hygiene items, shampoos, body lotions, and fabric re-fresheners. The process of the present invention relates to the use of 1,3-dioxane-4,6-diones as a synthon for the facile formation of P- ketoesters, especially P-ketoesters which comprise a tertiary alcohol subunit.

BACKGROUND OF THE INVENTION Esters which release perfume alcohols are currently of interest for their different odor profiles in products, as well as their odor profiles during and after use.

Particularly desirable are such esters which have a prolonged release characteristic from use in a home laundering process. Deposition onto a substrate, for example, onto fabric during the wash process followed by delayed release of the perfume after drying, is especially desirable. The challenge for using such esters include not only the right combination of storage stability and odor release profile, but also the challenge of making such esters in a cost effective manner.

P-Ketoesters are a particularly desirable class of materials, but such materials can present a particular challenge for a cost effective production. The di- functionality (ketone and carboxylic ester functionality in the same compound) of these compounds limits the types of reactions and conditions under which these compounds can be made. Add on the industrial scale and cost constraints that the use of specialty reactants add to the possible synthesis methods, and the large scale of production of such R-ketoester compounds for use in high volume consumer products becomes problematic.

Accordingly there remains a need in the art for a method for a simple, high yield, cost-effective means for preparing (3-ketoester fragrance pro-accords. In addition there is a need for convenient methods which produce ß-ketoesters capable of releasing tertiary alcohols inter alia dihydromyrcenol and linalool.

BACKGROUND ART The following relate to the preparation of ß-ketoesters from 1,3-dioxane-4,6- <BR> <BR> <BR> diones. Oikawa et al., J. Org. Chem., Vol 43, No 10,1978, pg. 2087; Capozzi et al., J. Org. Chem., Vol 58, No 27,1993, pg. 7932; Organic Synthesis Collective Volumes, pg 359, Oikawa et al., submitters; and Houghton et al.,"A Modified Preparation of ß-Keto Esters", Synthesis, pg 451, (1982).

SUMMARY OF THE INVENTION It has now been surprisingly discovered that molecules which releasably comprise fragrance raw material alcohols, namely P-ketoester fragrance pro-accords, can be suitably prepared from activated acyl adducts, for example, acid chlorides, and 1,3-dioxan-4,6-diones followed by reacting the product with a fragrance raw material alcohol. It is especially desirable that the fragrance raw material alcohols which become a subunit of the P-ketoester fragrance pro-accord are tertiary alcohols, for example, linalool and dihydromycenol.

The first aspect of the present invention relates to a process for preparing P- ketoester fragrance pro-accords comprising the steps of : a) reacting in the presence of a base a 1,3-dioxane-4,6-dione having the formula: wherein R1 and R2 are each independently C I-C 10 alkyl, C2-C 10 alkenyl, C7-C22 alkylenearyl, C6-C1o aryl, and mixtures thereof ; with an activated acyl group having the formula: wherein R3, R4, and R5 are each independently hydrogen, C1-C30 substituted or unsubstituted linear alkyl, C3-C30 substituted or unsubstituted branched alkyl, C3-C30 substituted or unsubstituted cyclic alkyl, Cl-C30 substituted or unsubstituted linear alkoxy, C3- C30 substituted or unsubstituted branched alkoxy, C3-C30 substituted or unsubstituted cyclic alkoxy, C2-C30 substituted or unsubstituted linear alkenyl, C3-C30 substituted or unsubstituted branched alkenyl, C3-C30 substituted or unsubstituted cyclic alkenyl, C2-C30 substituted or unsubstituted linear alkynyl, C3-C30 substituted or unsubstituted branched alkynyl, C6-C30 substituted or unsubstituted alkylenearyl; or R3, R4, and R5 can be taken together to form C6-C30 substituted or unsubstituted aryl; and mixtures thereof ; X is an acyl activating unit; to form an acyl 1,3-dioxane-4,6- dione, the enol tautomer of which having the formula: b) optionally, isolating said acyl 1,3-dioxane-4,6-dione; and c) reacting said acyl 1,3-dioxane-4,6-dione from step (a) or (b) with a fragrance raw material alcohol having the formula: ROH to form a (3-ketoester fragrance pro-accord having the formula: wherein R3, R4, and R5 are the same as defined herein above.

The present invention more specifically relates to the preparation of ß- ketoester fragrance pro-accords which comprise a secondary or tertiary alcohol subunit, more preferably a tertiary alcohol subunit. These and other objects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims.

All percentages, ratios and proportions herein are by weight, unless otherwise specified. All temperatures are in degrees Celsius (° C) unless otherwise specified. All documents cited are in relevant part, incorporated herein by reference.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for preparing (3-ketoester fragrance pro-accords from 1,3-dioxan-4,6-diones, preferably from 2,2-dimethyl-1,3-dioxan- 4,6-dione. Variations of the present process include isolation and purification of the intermediate acyl 1,3-dioxane-4,6-dione formed in Step (a) prior to subsequent reaction with a fragrance raw material alcohol. However, the formulator, depending upon several variables inter alia the structure of the final (3-ketoester, the amount of material to be produced, the type of process (i. e. batch reactions vs. continuous process) may produce the final product without isolation of the acyl 1,3-dioxan-4,6- dione intermediate.

For the purposes of the present invention the term"substituted"as it applies to linear alkyl, branched alkyl, cyclic alkyl, linear alkenyl, branched alkenyl, cyclic alkenyl, branched alkoxy, cyclic alkoxy, alkynyl, and branched alkynyl units are defined as"carbon chains which comprise substitutents other than branching of the carbon atom chain", for example, other than the branching of alkyl units (e. g. isopropyl, isobutyl). Non-limiting examples of"substituents"include hydroxy, C1- C 12 alkoxy, preferably methoxy; C3-C 12 branched alkoxy, preferably isopropoxy; C3-C12 cyclic alkoxy; nitrilo; halogen, preferably chloro and bromo, more preferably chloro; nitro; morpholino; cyano; carboxyl, non-limiting examples of which wherein R9 is Ci-Ci2 linear or branched alkyl);-S03-M+;-OS03-M+;-N (R10) 2; and- N+ (Rlo) 3X- wherein each R10 is independently hydrogen or Cl-C4 alkyl; and mixtures thereof ; wherein M is hydrogen or a water soluble cation; and X is chlorine, bromine, iodine, or other water soluble anion.

For the purposes of the present invention substituted or unsubstituted alkyleneoxy units are defined as moieties having the formula: wherein R7 is hydrogen; R8 is hydrogen, methyl, ethyl, and mixtures thereof ; the index x is from 1 to about 10.

For the purposes of the present invention substituted or unsubstituted alkyleneoxyalkyl are defined as moieties having the formula: wherein R7 is hydrogen, C1-Cl 8 alkyl, C1-C4 alkoxy, and mixtures thereof; R8 is hydrogen, methyl, ethyl, and mixtures thereof ; the index x is from 1 to about 10 and the index y is from 2 to about 18.

For the purposes of the present invention substituted or unsubstituted aryl units are defined as phenyl moieties having the formula: or a and (3-naphthyl moieties having the formula: wherein R7 and R8 can be substituted on either ring, alone or in combination, and R7 and R8 are each independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C1-C4 alkoxy, C3-C6 branched alkoxy, nitrilo, halogen, nitro, morpholino, cyano, carboxyl wherein R9 is Ci-Ci2 linear or branched alkyl),-S03-M+,-OS03-M+,-N (R10) 2, and- N+ (R10) 3X- wherein each R10 is independently hydrogen, Cl-C4 alkyl, or mixtures thereof ; and mixtures thereof, R7 and R8 are preferably hydrogen, Cl-C6 alkyl,- C02-M+,-S03-M+,-OS03'M+, and mixtures thereof; more preferably R7 or R8 is hydrogen and the other moiety is C1-C6; wherein M is hydrogen or a water soluble cation and X is chlorine, bromine, iodine, or other water soluble anion.

Examples of other water soluble anions include organic species such as fumarate, succinate, tartrate, oxalate and the like, inorganic species include sulfate, hydrogen sulfate, phosphate and the like.

For the purposes of the present invention substituted or unsubstituted alkylenearyl units are defined as moieties having the formula: wherein R7 and R8 are each independently hydrogen, hydroxy, Cl-C4 alkoxy, nitrilo, halogen, nitro, carboxyl ;- CONR92 ; wherein R9 is C 1-C 12 linear or branched alkyl), amino, alkylamino, and mixtures thereof, p is from 1 to about 14; M is hydrogen or a water soluble cation.

For the purposes of the present invention substituted or unsubstituted alkyleneoxyaryl units are defined as moieties having the formula: wherein R7 and R8 are each independently hydrogen, hydroxy, C 1-C4 alkoxy, nitrilo, halogen, nitro, carboxyl ;- CONR92; wherein R9 is C 1-C 12 linear or branched alkyl), amino, alkylamino, and mixtures thereof, q is from 1 to about 14; M is hydrogen or a water soluble cation.

The following summarizes the process of the present invention.

Step (a) Formation of a 2-acyl-1,3-dioxan-4,6-dione The first step of the process of the present invention relates to reacting an activated acyl moiety of the general formula: with a 1,3-dioxan-4,6-dione having the formula: to form a 2-acyl-1,3-dioxan-4,6-dione having, in its enol tautomer form, the formula: wherein RI and R2 are each independently C1-Clo alkyl, C2-C1o alkenyl, C7-C22 alkylenearyl, C6-C1o aryl, and mixtures thereof, preferably methyl; wherein R3, R4, and R5 are each independently hydrogen, C1-C30 substituted or unsubstituted linear alkyl, C3-C30 substituted or unsubstituted branched alkyl, C3-C30 substituted or unsubstituted cyclic alkyl, C1-C30 substituted or unsubstituted linear alkoxy, C3- C30 substituted or unsubstituted branched alkoxy, C3-C30 substituted or unsubstituted cyclic alkoxy, C2-C30 substituted or unsubstituted linear alkenyl, C3- C30 substituted or unsubstituted branched alkenyl, C3-C30 substituted or unsubstituted cyclic alkenyl, C2-C30 substituted or unsubstituted linear alkynyl, C3- C30 substituted or unsubstituted branched alkynyl, C6-C30 substituted or unsubstituted alkylenearyl; or R3, R4, and R5 can be taken together to form C6-C30 substituted or unsubstituted aryl; and mixtures thereof ; preferably two of R3, R4, and R5 are hydrogen and the remaining group is C1-C 10 linear or branched alkyl, C2-C 10 linear or branched alkenyl, preferably methyl and octyl, also preferably R3, R4, and R5 are taken together to form a substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, more preferably naphthyl.

X is an acyl activating unit. Non limiting examples of acyl activating units are acyloxy units having the formula-OC (O) R'which when taken together with the acyl moiety form a symmetrical or non-symmetrical anhydride, wherein R'is the same or different than the moiety which is formed by R3, R4, and R5. However, in cases where anhydride-like conditions are desired and formation of the acyl unit anhydride is either impractical or unobtainable, then the acyl carboxylic acid may be condensed with the 1,3-dioxan-4,6-dione in the presence of a condensing agent such as ethyl phosphonocyanidate. Other non-limiting examples of activated acyl units are acyl acid halides wherein X is chlorine, bromine, iodine, and mixtures thereof ; activated esters, for example, 4-nitrophenyl esters of the acyl unit defined by R3, R4, and R5.

The reaction of Step (a) of the present process is conducted in the presence of a base suitable to de-protonate the 2-position carbon of the selected 1,3-dioxan-4,6- dione. The acidity of the protons on the 2-carbon of the 1,3-dioxan-4,6-dione, and therefore the strength of the base necessary for reaction of Step (a), is governed by a number of factors, notably the structure of the dione itself. Bases suitable for use are selected from the group consisting of alkylamines, aromatic amines, polymeric amines, organo lithium compounds, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonate, alkali metal hydrides, alkaline earth metal hydrides, and mixtures thereof.

Non-limiting examples of bases suitable for use in the present invention are aromatic amines, for example, pyridine, picoline, lutidine, collidine; mono-, di-, and tri-alkylamines, for example, methyl amine, trimethylamine, triethanolamine; alkali metal and alkaline earth metal hydrides, for example, lithium hydride, sodium hydride; alkali metal alkoxides, for example, sodium ethoxide, sodium methoxide; alkali metal and alkaline earth metal carbonates and bicarbonates, for example sodium carbonate, potassium carbonate; organo metallic compounds, for example, butyl lithium, t-butyl lithium; alkali metal and alkaline earth metal hydroxides, for example, sodium hydroxide, potassium hydroxide. Preferred bases are pyridine and sodium hydride.

Depending upon the reaction conditions desired by the formulator, Step (a) can be conducted in the presence of a suitable solvent. Non-limiting examples of suitable solvents include dichloromethane, 1,2-dichloroethane, 1,2,3-trichloroethane, pentane, hexane, tetrahydrofuran, diethyl ether, benzene, toluene, xylene, 1,4- dioxane, acetonitrile, and mixtures thereof. In addition, the formulator may wish to adjust the reaction conditions to stabilize the formation of charged reaction species in which the use of solvents such as N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), hexamethyl phosphoramide (HMPA), and the like may be used alone or in combination with other suitable solvents. However, the formulator may generate the 1,3-dioxan-4,6-dione anion in water followed by isolation of the 1,3-dioxan-4,6-dione salt typically followed by thorough drying.

The reaction of Step (a) may be successfully conducted, depending upon the reactivity of the reagents, the scope of the reaction, and other mitigating parameters, at a temperature of from about-70° C, preferably from about-33° C, more preferably from about 0° C, most preferably from about 22 C (approximately room temperature), to about 100° C, preferably to about 80° C, more preferably to about 60 C, most preferably to about 40° C. The reaction of Step (a) may be conducted at more than one temperature, for example, during the addition of reagents the temperature of the reaction may be held at a first temperature, for example 0° C, and allowed to warm to a second temperature after the addition is complete.

Alternatively, the reaction may be warmed to generate the 1,3-dioxane-4,6-dione anion, then cooled during the addition of the activated acyl adduct.

The reaction of Step (a) may be conducted in any order which insures formation of the desired acyl 1,3-dioxan-4,6-dione intermediate. For example, in a first reaction vessel a suitable 1,3-dioxan-4,6-dione is reacted with sufficient base to form a 1,3-dioxan-4,6-dione anion. This can be accomplished by first charging a dry reaction vessel with an equivalent of a base such as sodium hydride in a suitable solvent such as tetrahydrofuran (THF). In a second reaction vessel a suitable 1,3- dioxan-4,6-dione is dissolved in a suitable solvent, for example, 2,2-dimethyl-1,3- dioxan-4,6-dione in a sufficient amount of dry THF Next the contents of the second reaction vessel is added to the contents of the first reaction vessel while cooling the admixture. Once the 1,3-dioxan-4,6-dione anion is sufficiently formed, in a third reaction vessel, an activated acyl unit is dissolve in a sufficient amount of solvent, for example, 2-naphthoyl chloride, is dissolved in THF, and this solution is subsequently added to the solution of 1,3-dioxan-4,6-dione anion.

However, in other embodiments of the present invention, it may be necessary to warm the admixture of base, suitable 1,3-dioxan-4,6-dione, and solvent in a reaction vessel in order to fully generate the 1,3-dioxan-4,6-dione anion prior to addition of the activated acyl unit.

Also included in Step (a) of the present invention is neutralization of any remaining base prior to proceeding to Steps (b) or (c). In a preferred embodiment of the present process, Step (a) is conducted under an inert atmosphere.

Step (b) Optionallv Isolating the 2-acvl-1, 3-dioxan-4, 6-dione formed in Step (a).

The formulator may choose to optionally isolate the 2-acyl-1,3-dioxan-4,6- dione form in Step (a) of the process of the present invention. Isolation may include, distillation, crystallization, chromatography and the like. However, it is not necessary that the intermediate 2-acyl-1,3-dioxan-4,6-dione be isolated prior to Step (c). <BR> <BR> <BR> <P> Step (c): Reacting the acvl 1, 3-dioxane-4, 6-dione formed in Step (a) or alternatively isolated in Step (b) with a fragrance raw material alcoho. l The 2-acyl-1,3-dioxan-4,6-dione form in Step (a) is then reacted with a fragrance raw material alcohol to form a (3-ketoester having the formula: wherein-OR represents a unit derived form a fragrance raw material alcohol an dR3, R4, and R5 are the same as define herein above.

For the purposes of the present invention"fragrance raw material alcohols" are herein defined as alcohols having a molecular weight of at least about 100 g/mol and which are useful in imparting an odor, fragrance, essence, or scent either alone or in combination with other"fragrance raw material alcohols".

Non-limiting examples of preferred fragrance raw material alcohols include 2,4-dimethyl-3-cyclohexene-1-methanol (Floralol), 2,4-dimethyl cyclohexane methanol (Dihydro floralol), 5,6-dimethyl-1-methylethenylbicyclo [2.2.1] hept-5-ene- 2-methanol (Arbozol), a, a,-4-trimethyl-3-cyclohexen-1-methanol (a-terpineol), 2,4,6-trimethyl-3-cyclohexene-1-methanol (Isocyclo geraniol), 4- (1- methylethyl) cyclohexane methanol (Mayol), a-3,3-trimethyl-2-norborane methanol, 1,1-dimethyl-1- (4-methylcyclohex-3-enyl) methanol, 2-phenylethanol, 2-cyclohexyl ethanol, 2- (o-methylphenyl)-ethanol, 2- (m-methylphenyl) ethanol, 2- (p- methylphenyl) ethanol, 1] hept-2-ene-2-ethanol (nopol), 2- (4-methylphenoxy)-ethanol, 3,3-dimethyl-A2-ß-norbornane ethanol (patchomint), 2- methyl-2-cyclohexylethanol, I- (4-isopropylcyclohexyl)-ethanol, 1-phenylethanol, 1,1-dimethyl-2-phenylethanol, 1,1-dimethyl-2- (4-methyl-phenyl) ethanol, 1- phenylpropanol, 3-phenylpropanol, 2-phenylpropanol (Hydrotropic Alcohol), 2- (cyclododecyl) propan-1-ol (Hydroxy-ambran), 2,2-dimethyl-3- (3-methylphenyl)- propan-1-ol (Majantol), 2-methyl-3-phenylpropanol, 3-phenyl-2-propen-1-ol (cinnamyl alcohol), 2-methyl-3-phenyl-2-propen-1-ol (methylcinnamyl alcohol), a- n-pentyl-3-phenyl-2-propen-1-ol (a-amyl-cinnamyl alcohol), ethyl-3-hydroxy-3- phenyl propionate, 2- (4-methylphenyl)-2-propanol, 3- (4-methylcyclohex-3- ene) butanol, 2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) butanol, 2-ethyl-4- (2,2,3-trimethyl-cyclopent-3-enyl)-2-buten-1-ol, 3-methyl-2-buten-1-ol (prenol), 2- methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol, ethyl 3- hydroxybutyrate, 4-phenyl-3-buten-2-ol, 2-methyl-4-phenylbutan-2-ol, 4- (4- hydroxyphenyl) butan-2-one, 4- (4-hydroxy-3-methoxyphenyl)-butan-2-one, 3- methyl-pentanol, 3-methyl-3-penten-1-ol, 1-(2-propenyl) cyclopentan-l-ol (plinol), 2-methyl-4-phenylpentanol (Pamplefleur), 3-methyl-5-phenylpentanol (Phenoxanol), 2-methyl-5-phenylpentanol, 2-methyl-5- (2,3- dimethyltricyclo [2.2.1.0 (2n6)] hept-3-yl)-2-penten-1-ol (santalol), 4-methyl-1-phenyl- 2-pentanol, 5- (2,2,3-trimethyl-3-cyclopentenyl)-3-methylpentan-2-ol (sandalore), (1- methyl-bicyclo [2.1.1] hepten-2-yl)-2-methylpent-1-en-3-ol, 3-methyl-1- phenylpentan-3-ol, 1,2-dimethyl-3- (l-methylethenyl) cyclopentan-l-ol, 2-isopropyl- 5-methyl-2-hexenol, cis-3-hexen-1-ol, trans-2-hexen-1-ol, 2-isoproenyl-4-methyl-4- hexen-1-ol (Lavandulol), 2-ethyl-2-prenyl-3-hexenol, 1-hydroxymethyl-4-iso- propenyl-1-cyclohexene (Dihydrocuminyl alcohol), 1-methyl-4- isopropenylcyclohex-6-en-2-ol (carvenol), 6-methyl-3-isopropenylcyclohexan-1-ol (dihydrocarveol), 1-methyl-4-iso-propenylcyclohexan-3-ol, 4-isopropyl-1- methylcyclohexan-3-ol, 4-tert-butylcyclo-hexanol, 2-tert-butylcyclohexanol, 2-tert- butyl-4-methylcyclohexanol (rootanol), 4-isopropyl-cyclohexanol, 4-methyl-1- (1- methylethyl)-3-cyclohexen-1-ol, 2- (5,6,6-trimethyl-2-norbornyl) cyclohexanol, isobornylcyclohexanol, 3,3,5-trimethylcyclohexanol, 1-methyl-4- isopropylcyclohexan-3-ol, 1-methyl-4-isopropylcyclohexan-8-ol (dihydroterpineol), 1,2-dimethyl-3- (1-methylethyl) cyclohexan-1-ol, heptanol, 2,4-dimethylheptan-1-ol, 6-heptyl-5-hepten-2-ol (isolinalool), 2,4-dimethyl-2,6-heptandienol, 6,6-dimethyl-2- oxymethyl-bicyclo [3.1.1] hept-2-ene (myrtenol), 4-methyl-2,4-heptadien-1-ol, 3,4,5,6,6-pentamethyl-2-heptanol, 3,6-dimethyl-3-vinyl-5-hepten-2-ol, 6,6-dimethyl- 3-hydroxy-2-methylenebicyclo [3.1.1] heptane, 1,7,7-trimethylbicyclo [2.2.1] heptan- 2-ol, 2,6-dimethylheptan-2-ol (dimetol), 2,6,6-trimethylbicyclo [1.3.3] heptan-2-ol, octanol, 2-octenol, 2-methyloctan-2-ol, 2-methyl-6-methylene-7-octen-2-ol (myrcenol), 7-methyloctan-1-ol, 3,7-dimethyl-6-octenol, 3,7-dimethyl-7-octenol, 3,7-dimethyl-6-octen-1-ol (citronellol), 3,7-dimethyl-2,6-octadien-1-ol (geraniol), 3,7-dimethyl-2,6-octadien-1-ol (nerol), 3,7-dimethyl-7-methoxyoctan-2-ol (osyrol), (linalool), 3,7-dimethyloctan-1-ol (pelargol), 3,7- dimethyloctan-3-ol (tetrahydrolinalool), 2,4-octadien-1-ol, 3,7-dimethyl-6-octen-3- ol (dihydrolinalool), 2,6-dimethyl-7-octen-2-ol (dihydromyrcenol), 2,6-dimethyl- 5,7-octadien-2-ol, 4,7-dimethyl-4-vinyl-6-octen-3-ol, 3-methyloctan-3-ol, 2,6- dimethyloctan-2-ol, 2,6-dimethyloctan-3-ol, 3,6-dimethyloctan-3-ol, 2,6-dimethyl-7- octen-2-ol, 2,6-dimethyl-3,5-octadien-2-ol (muguol), 3-methyl-1-octen-3-ol, 7- hydroxy-3,7-dimethyloctanal, 3-nonanol, 2,6-nonadien-1-ol, cis-6-nonen-1-ol, 6,8- dimethylnonan-2-ol, 3- (hydroxymethyl)-2-nonanone, 2-nonen-1-ol, 2,4-nonadien-1- ol, decanol, 9-decenol, 2-benzyl-M-dioxa-5-ol, 2- decen-1-ol, 2,4-decadien-1-ol, 4-methyl-3-decen-5-ol, 3,7,9-trimethyl-1,6-decadien- 3-ol (isobutyl linalool), undecanol, 2-undecen-1-ol, 10-undecen-1-ol, 2-dodecen-1- ol, 2,4-dodecadien-1-ol, 10-dodecatrien-1-ol (farnesol), 3,7,11- trimethyl-1,6,10,-dodecatrien-3-ol (nerolidol), 3,7,11, 15-tetramethylhexadec-2-en-1- ol (phytol), 3,7,11,15-tetramethylhexadec-1-en-3-ol (iso phytol), benzyl alcohol, p- methoxy benzyl alcohol (anisyl alcohol), para-cymen-7-ol (cuminyl alcohol), 4- methyl benzyl alcohol, 3,4-methylenedioxy benzyl alcohol, methyl salicylate, benzyl salicylate, cis-3-hexenyl salicylate, n-pentyl salicylate, 2-phenylethyl salicylate, n- hexyl salicylate, 2-methyl-5-isopropylphenol, 4-ethyl-2-methoxyphenol, 4-allyl-2- methoxyphenol (eugenol), 2-methoxy-4- (1-propenyl) phenol (isoeugenol), 4-allyl- 2,6-dimethoxy-phenol, 4-tert-butylphenol, 2-ethoxy-4-methylphenol, 2-methyl-4- vinylphenol, 2-isopropyl-5-methylphenol (thymol), pentyl-ortho-hydroxy benzoate, ethyl 2-hydroxy-benzoate, methyl 2,4-dihydroxy-3,6-dimethylbenzoate, 3-hydroxy- 5-methoxy-1-methylbenzene, 2-tert-butyl-4-methyl-1-hydroxybenzene, 1-ethoxy-2- hydroxy-4-propenylbenzene, 4-hydroxytoluene, 4-hydroxy-3-methoxybenzaldehyde, 2-ethoxy-4-hydroxybenzaldehyde, decahydro-2-naphthol, 2,5,5-trimethyl-octahydro- 2-naphthol, 1,3,3-trimethyl-2-norbornanol (fenchol), 3a, 4,5,6,7,7a-hexahydro-2,4- dimethyl-4,7-methano-lH-inden-5-ol, 3a, 4,5,6,7,7a-hexahydro-3,4-dimethyl-4,7- methano-1 H-inden-5-ol, 2-methyl-2-vinyl-5-(1-hydroxy-1-methylethyl)(1-hydroxy-1-met hylethyl) tetra- hydrofuran, P-caryophyllene alcohol, vanillin, ethyl vanillin, and mixtures thereof.

More preferably, the fragrance raw material alcohol is selected from the group consisting of cis-3-hexen-1-ol, hawthanol [admixture of 2- (o-methylphenyl)- ethanol, 2- (m-methylphenyl) ethanol, and 2- (p-methylphenyl) ethanol], heptan-1-ol, decan-1-ol, 2,4-dimethyl cyclohexane methanol, 4-methylbutan-1-ol, 2,4,6- trimethyl-3-cyclohexene-1-methanol, 4- (l-methylethyl) cyclohexane methanol, 3- (hydroxy-methyl)-2-nonanone, octan-1-ol, 3-phenylpropanol, Rhodinol 70 [3,7- dimethyl-7-octenol, 3,7-dimethyl-6-octenol admixture], 9-decen-1-ol, a-3,3- trimethyl-2-norborane methanol, 3-cyclohexylpropan-l-ol, 4-methyl-1-phenyl-2- pentanol, 3,6-dimethyl-3-vinyl-5-hepten-2-ol, phenyl ethyl methanol; propyl benzyl methanol, 1-methyl-4-isopropenylcyclohexan-3-ol, 4-isopropyl-1- methylcyclohexan-3-ol (menthol), 4-tert-butylcyclohexanol, 2-tert-butyl-4- methylcyclohexanol, 4-isopropylcyclo-hexanol, trans-decahydro-p-naphthol, 2-tert- butylcyclohexanol, 3-phenyl-2-propen-1-ol, 10-dodecatrien-1- ol, 3,7-dimethyl-2,6-octadien-1-ol (geraniol), 3,7-dimethyl-2,6-octadien-1-ol (nerol), 4-methoxybenzyl alcohol, benzyl alcohol, 4-allyl-2-methoxyphenol, 2-methoxy-4- (1-propenyl) phenol, vanillin, and mixtures thereof.

Step (c) of the present process can be conducted in the presence of a suitable solvent or an excess amount of the fragrance raw material alcohol may be used as a solvent. Non-limiting examples of suitable solvents include dichloromethane, 1,2- dichloroethane, 1,2,3-trichloroethane, pentane, hexane, tetrahydrofuran, diethyl ether, benzene, toluene, xylene, 1,4-dioxane, acetonitrile, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), hexamethyl phosphoramide (HMPA), and mixtures thereof.

The reaction of Step (c) may be successfully conducted, depending upon the reactivity of the reagents, the scope of the reaction, and other mitigating parameters, at a temperature of from about 0° C, preferably from about 22° C (approximately room temperature), more preferably from about 40 C, to about 200° C, preferably to about 150° C, more preferably to about 1000 C, most preferably to about 80° C.

Included in Step (c) of the present invention is a provision for neutralizing any base present from Step (a) above. In a preferred embodiment of the present process, Step (c) is conducted under an inert atmosphere. In addition, an amount of a suitable acid catalyst may be added to the reaction of Step (c).

The product thus obtained from Step (c) of the present process can be purifie by any conventional means depending upon the form physical form of the obtained P-ketoester. Non-limiting examples include chromatography, crystalizedion, distillation, sublimation, etc.

The following non-limiting example illustrates the present process.

Preparation of 3S7-dimethvl-1*6-octadien-3-yl 3-(ß-naphthvl)-3-oxo-propionate (linalyl (2-naphthoyl) acetoacetate) Sodium hydride (1.26 g, 0.057 mol, 95%) is charged to a 250 mL three- necked round-bottomed flask fitted with a magnetic stirrer, ice bath, addition funnel, internal thermometer and argon inlet. The contents of the reaction vessel are slurried with 50 mL of tetrahydrofuran (THF) and subsequently cooled to 0 °C. 2,2- dimethyl-1,3-dioxan-4,6-dione (Meldrum's acid) (3.78 g, 0.026 mol) is dissolved in 20 mL of THF and the solution is subsequently added over 15 min. The evolution of gas indicates the reaction is ensuing. After 30 min, 2-naphthoyl chloride (5.00 g, 0.026 mol) which is dissolved in 30 mL of THF is added over 15 min. The mixture is allowed to warm to room temperature and stirred for 72 h. A solution of 3,7- dimethyl-1,6-octadien-3-ol (linalool) (4.05 g, 0.026 mol) dissolved in 30 mL of THF is added over 30 min. The mixture is heated to reflux for 18 h. The cooled mixture is poured into 100 mL of water and extracted with ether (50 mL) three times. The organic layers are washed with saturated NaHC03 solution, water, dried over MgSO4, filtered, concentrated by rotary evaporation and purified by flash chromatography to yield 3-(ß-naphthyl)-3-oxo- propionate.