Introduction

[0001] This application claims the benefit of priority of U.S. Provisional Application Nos. 61/587,716, filed January 18, 2012; 61/587,720, filed January 18, 2012; 61/587,722, filed January 18, 2012; 61/587,726, filed January 18, 2012; 61/587,728, filed January 18, 2012; 61/587,740, filed January 18, 2012; 61/587,742, filed January 18, 2012; 61/587,747, filed January 18, 2012; 61/587,749, filed January 18, 2012; 61/587,753, filed January 18, 2012; 61/587,754, filed January 18, 2012; 61/587, 755, . filed January 18, 2012; 61/587,757, filed January 18, 2012; and 61/587,759, filed January 18, 2012, the contents of each of which are incorporated herein by reference in their entirety.

Background of the Invention

[0002] There is an ongoing need in the fragrance industry to provide new chemicals to give perfumers and other persons the ability to create new fragrances for perfumes, colognes and personal care products. Those with skill in the art appreciate how differences in the chemical structure of the molecule can result in significant differences in the odor, notes and characteristics of a molecule. These variations and the ongoing need to discover and use the new chemicals in the development of new fragrances allow the perfumers to apply the new compounds in creating new fragrances.

Summary of the Invention

[0003] The present invention provides novel compounds and their unexpected advantageous use in enhancing, improving or modifying the fragrance of perfumes, colognes, toilet water, fabric care products, personal products and the like.

[0004] In certain embodiments, the compound is 1- (2,4,6- trimethyl-cyclohex-3-enyl) -propan-l-one; 2- (3-methyl- butyl) -3-vinyl-cyclopentanone; 2,5, 5-trimethyl-2-propyl-

[1,3] dioxane; 1 _/ 2, 4-trimethyl-bicyclo [2.2.1] heptane-2- carboxylic acid methyl ester 8-ethoxy-2 , 6-dimethyl-nona- 2, 6-diene; 4-cyclopropylmethoxymethyl-5-methyl~cyclohexene; cyclopropanecarboxylic acid 1-methyl-hexyl ester; 3- isopropenyl-6-methyl-2-propenyl-tetrahydro-pyran; acetic acid 3-isopropyl-l, 2-dimethyl-cyclopentyl ester; 4- (2, 4- dimethyl-cyclohex-3-enylidene) -butan-2-one; 1,1,3,3,5- pentamethyl-1 , 3, 3a, 4, 7, 7a-hexahydro-isobenzofuran; or 2-

(hex-3-enyl ) -5-methyl-tetrahydro-furan .

[0005] In other embodiments, the compound is a 2-oxa- bicyclo [2.2.2 ] octane represented by Formula II:

Formula II

wherein R ¹ is selected from the group consisting of hydrogen and methyl; and R ² is a C1-C3 alkyl group. In' particular embodiments, the compound of Formula II is 4-isopropyl-l, 5- dimethyl-2-oxa-bicyclo [2.2.2] octane or 4- ( 1 , 2-dimethyl- propyl) -l-methyl-2-oxa-bicyclo [2.2.2] octane.

[0006] In further embodiments, the compound is an octahydro-benzofuran represented by Formula VII:

Formula VII

wherein R ³ , R ⁴ R ⁵ , and R ⁶ are independently selected from the group consisting of hydrogen and methyl; and R ⁷ is a C ₁ -C ₃ alkyl group. In accordance with some embodiments, the compound of Formula II is 2 , 2 , 3a, 7-tetramethyl-octahydro- benzofuran or 3a-isopropyl-2 , 6-dimethyl-octahydro- benzofuran .

[0007] Another embodiment of the present invention relates to a fragrance composition containing one or more of the novel compounds provided above.

[0008] Another embodiment of the present invention relates to a fragrance product containing one or more of the compounds provided above .

[0009] Another embodiment of the present invention relates to a method of improving, enhancing or modifying a fragrance formulation through the addition of an olfactory acceptable amount of one or more of the compounds provided above .

[0010] These and other embodiments of the present invention will be apparent by reading the following specification.

Detailed Description of the Invention

[0011]- 1- (2, 4, 6-Trimethyl-cyclohex-3-enyl) -propan-l-one represented by Formula I has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, animalic, civet, chrysanthemum leaves, and honey notes .

Formula I

[0012] Another embodiment of the present invention relates to novel 2-oxa-bicyclo [2.2.2] octanes that exhibit unexpected strong fragrance effect of herbal, camphor, woody, minty, patchouli, anisic, green, powdery, and fruity characters, and a method of improving, enhancing or modifying a fragrance formulation through the addition of an olfactory acceptable amount of an 2-oxa- bicyclo [2.2.2] octane represented b Formula II:

. Formula II

wherein R ¹ is selected from the group consisting of hydrogen and methyl; and R ² is a C ₁ -C ₃ alkyl group.

[0013] In particular embodiments, a compound of Formula II has the

Formula Ila Formula lib Those with the skill in the art will recognize that Formula Ha represents 4-isopropyl-l, 5-dimethyl-2-oxa- bicyclo [2.2.2] octane; and Formula lib represents 4- (1,2- dimethyl-propyl) -l-methyl-2-oxa-bicyclo [2.2.2] octane. 4- Isopropyl-1, 5-dimethyl-2-oxa-bicyclo [2.2.2] octane has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, herbal, camphor, woody, minty, and patchouli aspects, whereas 4- (1,2- Dimethyl-propyl) -l-methyl-2-oxa-bicyclo [2.2.2] octane has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, woody, anisic, green, powdery, and fruity notes.

[0014] 2- (3-Methyl-butyl) -3-vinyl-cyclopentanone

represented by Formula III has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, lactonic, peach, buttery, floral, fruity, marigold, green, herbaceous, and minty notes. Therefore, this compound is also of use in improving, enhancing or modifying a fragrance formulation.

Formula III

[0015] 2, 5, 5-Trimethyl-2-propyl- [1, 3] dioxane represented by Formula IV has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, fruity and anise notes. Therefore, an olfactory acceptable amount of this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula IV

[0016] 1,2, 4-trimethyl-bicyclo [2.2.1] heptane-2-carboxylic acid methyl ester represented by Formula V has been surprisingly found to possess a strong and unexpected fragrance effect of woody, pine, camphor, herbal, and earthy notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation .

Formula V

[0017] 8-Ethoxy-2 , 6-dimethyl-nona-2 , 6-diene represented by Formula VI has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, grapefruit, citrus, fresh, lemonile, lemonalva, and metallic notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation .

Formula VI

[0018] Another embodiment of the present invention relates to novel octahydro-benzofurans that exhibit unexpected strong fragrance effect of herbal, sweet, camphor, woody, fresh, green, spice, flora, eucalyptus, and slight piney notes, and a method of improving, enhancing or modifying a fragrance formulation through the addition of an olfactory acceptable amount of octahydro-benzofurans represented by Formula VII:

Formula VII

wherein R ³ , R ⁴ R ⁵ , and R ⁶ are independently selected from the group consisting of hydrogen and methyl; and R ⁷ is a C ₁ -C3 alkyl group.

[0019] In particular embodiments, the compound of Formula VII has the structure of Formula Vila or Vllb:

Formula Vila Formula Vllb

Those with the skill in the art will recognize that Formula Vila represents 2 , 2 , 3a, 7-tetramethyl-octahydro-benzofuran; and Formula Vllb represents 3a-isopropyl-2 , 6-dimethyl- octahydro-benzofuran . 2,2, 3a, 7-Tetramethyl-octahydro- benzofuran has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, herbal, sweet, camphor, woody, fresh, and green notes, whereas 3a-isopropyl-2 , 6-dimethyl-octahydro-benzofuran has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, cedar wood, green, spice, flora, eucalyptus, and slight piney notes. [0020] 4-Cyclopropylmethoxymethyl-5-methyl-cyclohexene represented by Formula VIII has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong fruity and green notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula VIII

[0021] Cyclopropanecarboxylic acid l-methyl-hexyl ester represented by Formula IX has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong fruity, herbal, seaweed, chamomile, and ambrette seed notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation .

Formula IX

[0022] 3-Isopropenyl-6-methyl-2-propenyl-tetrahydro-pyran represented by Formula X has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong woody, fresh, cinnamon, and spicy notes. Therefore, this compound is of use in a method of improving, enhancing or modif ing a fragrance formulation.

Formula X

[0023] Acetic acid 3-isopropyl-l, 2-dimethyl-cyclopentyl ester represented by Formula XI has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong woody, fresh, cinnamon, and spicy notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula XI

[0024] 4- (2, -Dimethyl-cyclohex-3-enylidene) -butan-2-one represented by Formula XII has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong woody and spicy notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula XII

[0025] 1, 1, 3, 3, 5-Pentamethyl-l, 3, 3a, 4,7, 7a-hexahydro- isobenzofuran represented by Formula XIII has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong woody, camphor, fresh and mushroom notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula XIII

[0026] 2- (Hex-3-enyl ) -5-methyl-tetrahydro-furan represented by Formula XIV has been surprisingly found to possess strong and unexpected fragrance effect such as, for example, strong floral and vegetable notes. Therefore, this compound is of use in a method of improving, enhancing or modifying a fragrance formulation.

Formula XIV

[0027] It is intended that the compounds described herein include isomeric mixtures of such compounds, as well as those isomers that may be separated using techniques known to those having skill in the art. Suitable techniques include chromatography such as high performance liquid chromatography, referred to as HPLC, and particularly silica gel chromatography and gas chromatography trapping known as GC trapping. Yet, commercial products are mostly offered as isomeric mixtures.

[0028] The preparation of the compounds of the present invention is detailed in the Examples. Materials were purchased from Aldrich Chemical Company unless noted otherwise .

[0029] The use of the compounds of the present invention is widely applicable in current perfumery products, including the preparation of perfumes and colognes, the perfuming of personal care products such as soaps, shower gels, and hair care products, fabric care products, air fresheners, and cosmetic preparations. The present invention can also be used to perfume cleaning agents, such as, but not limited to detergents, dishwashing materials, scrubbing compositions, window cleaners and the like.

[0030] In these preparations, the compounds of the present invention can be used alone or in combination with other perfuming compositions, solvents, adjuvants and the like. The nature and variety of the other ingredients that can also be employed are known to those with skill in the art. Many types of fragrances can be employed in the present invention, the only limitation being the compatibility with the other components being employed. Suitable fragrances include but are not limited to fruits such as almond, apple, cherry, grape, pear, pineapple, orange, strawberry, raspberry; musk, flower scents such as lavender-like, roselike, iris-like, carnation-like. Other pleasant scents include herbal and woodland scents derived from pine, spruce and other forest smells. Fragrances may also be derived from various oils, such as essential oils, or from plant materials such as peppermint, spearmint and the like.

[0031] A list of suitable fragrances is provided in US Pat. No. 4,534,891, the contents of which are incorporated by reference as if set forth in its entirety. Another source of suitable fragrances is found in Perfumes, Cosmetics and Soaps, Second Edition, edited by W. A. Poucher, 1959. Among the fragrances provided in this treatise are acacia, cassie, chypre, cyclamen, fern, gardenia, hawthorn, heliotrope, honeysuckle, hyacinth, jasmine, lilac, lily, magnolia, mimosa, narcissus, freshly-cut hay, orange blossom, orchid, reseda, sweet pea, trefle, tuberose, vanilla, violet, wallflower, and the like.

[0032] The compounds of the present invention can be used in combination with a complementary fragrance compound. The term "complementary fragrance compound" as used herein is defined as a fragrance compound selected from the group consisting of 2- [ ( 4-methylphenyl) methylene] -heptanal

(Acalea) , iso-amyl oxyacetic acid allylester (Allyl Amyl Glycolate) , (3, 3-dimethylcyclohexyl) ethyl ethyl propane- 1,3-dioate (Applelide) , (E/Z ) -1-ethoxy-l-decene (Arctical) , 2-ethyl-4- { 2 , 2 , 3-trimethyl-3-cyclo-penten-l-yl) -2-buten-l- ol (Bacdanol), 2-methyl-3- [ (1, 7, 7- trimethylbicyclo [2.2.1] hept-2-yl) oxy] exo-l-propanol (Bornafix) , 1,2,3,5,6, 7-hexahydro-l, 1,2,3, 3-pentamethyl-4H- inden-4-one (Cashmeran) , trimethylcyclopentenylmethyloxabicyclooctane (Cassiffix) , 1, l-dimethoxy-3, 7-dimethyl-2, 6-octadiene (Citral DMA), 3,7- dimethyl-6-octen-l-ol (Citronellol) , 3A, 4, 5, 6, 7, 7A- hexahydro-4 , 7-methano-liJ-inden-5/6-yl acetate (Cyclacet) , 3A, 4,5,6,7, 7A-hexahydro-4 , 7-methano-lH-inden-5/6-yl

propinoate (Cyclaprop) , 3A, 4 , 5, 6, 7 , 7A-hexahydro-4 , 7- methano-lG-inden-5/6-yl butyrate (Cyclobutanate) , 1- (2,6,6- trimethyl-3-cyclohexen-l-yl) -2-buten-l-one (Delta Damascone) , 3- ( 4-ethylphenyl ) -2 , 2-dimethyl propanenitrile (Fleuranil), 3- (O/P-ethylphenyl) 2, 2-dimethyl propionaldehyde (Floralozone) , tetrahydro-4-methyl-2- (2- methylpropyl) -2H-pyran-4-ol (Floriffol) , 1,3,4,6,7,8- hexahydro-4 , 6,6,7,8, 8-hexamethylcyclopenta-gamma-2- benzopyran (Galaxolide) , 1- (5, 5-dimethyl-l-cyclohexen-l- yl) ent-4-en-l-one (Galbascone) , E/Z-3, 7-dimethyl-2 , 6- octadien-l-yl acetate (Geranyl Acetate), D-methyl-l , 3- benzodioxole-5-propanal (Helional) , 1- (2, 6, 6-trimethyl-2- cyclohexen-l-yl) -1, 6-heptadien-3-one (Hexalon) , (Z)-3- hexenyl-2-hydroxybenzoate (Hexenyl Salicylate, CIS-3) , 4- (2, 6, 6-trimethyl-2-cyclohexen-l-yl) -3-buten-2-one (Ionone □) , 1- (1,2, 3, 4, 5, 6, 7, 8-octahydro-2, 3, 8, 8-tetramethyl-2- naphthalenyl) -ethan-l-one (Iso E Super), methyl 3-oxo-2- pentylcyclopentaneacetate (Kharismal) , 2 , 2 , 4-trimethyl-4~ phenyl-butanenitrile (Khusinil) , 3, 4, 5, 6, 6-pentamethylhept- 3-en-2-one (Koavone) , 3/4- (4-hydroxy-4-methyl-pentyl) cyclohexene-l-carboxaldehyde (Lyral) , 3-methyl-4- (2, 6, 6- trimethyl-2-cyclohexen-l-yl) -3-buten-2-one (Methyl Ionone □) , 1- (2, 6, 6-trimethyl-2-cyclohexen-l-yl) pent-l-en-3-one (Methyl Ionone □ Extra, Methyl Ionone N) , 3-methyl-4- phenylbutan-2-ol (Muguesia) , cyclopentadec-4-en-l-one (Musk Z4) , 3, 3, 4, 5, 5-pentamethyl-ll, 13- dioxatricyclo [7.4.0.0<2, 6>] tridec-2 (6) -ene (Nebulone) , 3,7- dimethyl-2 , 6-octadien-l-yl acetate (Neryl Acetate), 3,7- dimethyl-1, 3, 6-octatriene (Ocimene) , ortho-tolylethanol (Peomosa) , 3-methyl-5-phenylpentanol (Phenoxanol) , 1- methyl-4- (4-methyl-3-pentenyl) cyclohex-3-ene-l- carboxaldehyde (Precyclemone B) , 4-methyl-8-methylene-2- adamantanol (Prismantol) , 2-ethyl-4- (2, 2, 3-trimethyl-3- cyclopenten-l-yl) -2-buten-l-ol (Sanjinol), 2-methyl-4- (2,2, 3-trimethyl-3-cyclopenten-l-yl) -2-buten-l-ol

(Santaliff) , Terpineol, 2 , 4-dimethyl-3-cyclohexene-l- carboxaldehyde (Triplal) , decahydro-2 , 6, 6, 7 , 8 , 8-hexamethyl- 2H-indeno [4 , 5-B] furan (Trisamber) , 2-tert-butylcyclohexyl acetate (Verdox) , 4-tert-butylcyclohexyL acetate

(Vertenex) , acetyl cedrene (Vertofix) , 3,6/4,6- dimethylcyclohex-3-ene-l-carboxaldehyde (Vertoliff) , and (3Z) -1- [ (2-methyl-2-propenyl ) oxy] -3-hexene (Vivaldie) .

[0033] The term "hydrocarbon group" means a chemical group that contains only hydrogen and carbon atoms. The hydrocarbon group of the present invention can be a straight, branched and/or cyclic, saturated or unsaturated group .

[0034] The terms "fragrance formulation", "fragrance composition", and "perfume composition" mean the same and refer to a consumer composition that is a mixture of compounds including, for example, alcohols, aldehydes, ketones, esters, ethers, lactones, nitriles, natural oils, synthetic oils, and mercaptans, which are admixed so that the combined odors of the individual components produce a pleasant or desired fragrance. The fragrance formulation of the present invention is a consumer composition including a compound of the present invention. The fragrance formulation of the present invention includes a compound of the present invention and can further include a complementary fragrance compound as defined above.

[0035] The term "fragrance product" means a consumer product that adds a fragrance or masks a malodor. Fragrance products may include, for example, perfumes, colognes, personal care products such as soaps, shower gels, and hair care products, fabric products, air fresheners, cosmetic preparations, and perfume cleaning agents such as detergents, dishwashing materials, scrubbing compositions, and window cleaners. The fragrance product of the present invention is a consumer product that contains a compound of the present invention. The fragrance product of the present invention contains a compound of the present invention and can further include a complementary fragrance compound as defined above.

[0036] The term "improving" in the phrase "improving, enhancing or modifying a fragrance formulation" is understood to mean raising the fragrance formulation to a more desirable character. The term "enhancing" is understood to mean making the fragrance formulation greater in effectiveness or providing the fragrance formulation with an improved character. The term "modifying" is understood to mean providing the fragrance formulation with a change in character. [0037] The term "olfactory acceptable amount" is understood to mean the amount of a compound in a fragrance formulation, wherein the compound will contribute its individual olfactory characteristics. However, the olfactory effect of the fragrance formulation will be the sum of effect of each of the fragrance ingredients. Thus, the compound of the present invention can be used to improve or enhance the aroma characteristics of the fragrance formulation, or by modifying the olfactory reaction contributed by other ingredients in the formulation. The olfactory acceptable amount may vary depending on many factors including other ingredients, their relative amounts and the olfactory effect that is desired.

[0038] The amount of the compounds of the present invention employed in a fragrance formulation varies from about 0.005 to about 70 weight percent, preferably from 0.005 to about 50 weight percent, more preferably from about 0.5 to about 25 weight percent, and even more preferably from about 1 to about 10 weight percent. Those with skill in the art will be able to employ the desired amount to provide desired fragrance effect and intensity. In addition to the compounds of the present invention, other materials can also be used in conjunction with the fragrance formulation. Well known materials such as surfactants, emulsifiers, polymers to encapsulate the fragrance can also be employed without departing from the scope of the present invention.

[0039] When used in a fragrance formulation these ingredients provide additional notes to make a fragrance formulation more desirable and noticeable, and add the perception of value. The odor qualities found in these materials assist in beautifying and enhancing the finished accord as well as improving the performance of the other materials in the fragrance.

[0040] The following are provided as specific embodiments of the present invention. Other modifications of this invention will be readily apparent to those skilled in the art. Such modifications are understood to be within the scope of this invention. As used herein all percentages are weight percent unless otherwise noted, ppm is understood to stand for parts per million, L is understood to be liter, mL is understood to be milliliter, Kg is understood to be kilogram, g is understood to be gram, mol is understood to be mole, psi is understood to be pound-force per square inch, and mmHg be millimeters (mm) of mercury (Hg) . IFF as used in the examples is understood to mean International Flavors & Fragrances Inc., New York, NY, USA. he invention will be further described in the following examples, which do not limit the scope of the invention described in the claims .

Example 1: Preparation of 1- (2 ,4 , 6-Trimethyl-Cyclohex-3-Enyl) - Prop n-l-One (Formula I)

1 -(2,4,6-trimethyl-cyclohex 1 -(2,4,6-trimethyl-cyclohex -3-enyl)-propan-1-ol -3~enyl)-propan-1 -one

[0041] 1- (2, 4, 6-Trimethyl-cyclohex-3-enyl) -propan-l-ol (182 g, 1.0 mol) dissolved in acetone (400 mL) was added dropwise to a solution of chromium trioxide (CrC>3 , 108 g, 1.08 mol) in aqueous sulfuric acid (H ₂ S0 ₄ , 400 mL, 172 g in water) at -10 °C. The resulting mixture was aged for 2 hours as the mixture warmed to 0°C. The mixture was then diluted with water and extracted with toluene. The organic layer was concentrated by rotary evaporation and distilled via fractionation to provide 1- (2, 4, 6-trimethyl-cyclohex-3- enyl) -propan-l-one (113 g, 63% yield) as a colorless liquid. ¹ H NMR and ¹³ C NMR data matched those reported previously (See, J. Am. Chem. Soc. 1997, 119, pages 3507- 3512). 1- (2, 4, 6-Trimethyl-cyclohex-3-enyl) -propan-l-one was described as having animalic, civet, chrysanthemum leaves, and honey characteristics.

Example 2: Preparation of 3-Methyl-2-Methylene- Butyraldehyde

3-methyl-butyraldehyde 3-methyl-2-methylene-butyraldehyde

[0042] Di-n-butylamine (75 g, 0.58 mol) and acetic acid (70 g, 1.16 mol) were mixed in a 5 L round bottom flask. Formaldehyde (1.411 Kg, 17.4 mol) was then added and the resulting mixture was heated to 50 °C. Isovaleraldehyde (1 Kg, 11.6 mol) was fed into the reaction mixture at 50 °C for over 2.5 hours. After the feed was completed, gas chromatograph analysis (GC analysis) indicated that the reaction was 92% complete. The reaction mixture containing 3-methyl-2-methylene-butyraldehyde was cooled to room temperature and washed with a saturated sodium carbonate solution.

Example 3: Preparation of l-Isopropyl-2 , 4-Dimethyl- Cyclohex-3-Enecarbaldehyde

3-methyl-2-methylene 1-isopropyl-2,4-dimethyl- -butyraldehyde cyclohex-3-enecarbaldehyde

[0043] ethylpentadiene (428 g, 5.1 mol) was placed in a stainless-steel autoclave containing the reaction mixture of 3-methyl-2-methylene-butyraldehyde (500 g, 5.1 mol, obtained in Example 2) and heated to 200 °C. The reaction was monitored by GC analysis and stopped when a 75% conversion rate was observed. The resulting mixture was then cooled to room temperature and removed from the autoclave. The crude product l-isopropyl-2 , 4-dimethyl- cyclohex-3-enecarbaldehyde was dissolved in toluene and azeotroped to dryness under a reduced pressure.

Example 4 : Preparation of (l-Isopropyl-2 , 4-Dimethyl- Cyclohex-3-Enyl) -Methanol

1 -isopropyI-2,4-dimethyl- (1 -isopropyl-2,4-dimethyl- cyclohex-3-enecarbaldehyde cyclohex~3-enyl)-methanol

[0044] Isopropylmagnesium chloride ( (CH ₃ ) ₂ HC gCl) in tetrahydrofuran (THF) (1.6 L, 3.2 mol) was loaded into a flame-dried 5 L round bottom flask. Additional THF (1 L) was added. l-Isopropyl-2 , 4-dimethyl-cyclohex-3- enecarbaldehyde (obtained in Example 3) was then fed for over 2 hours at 0°C under nitrogen. The reaction mixture was aged at 0°C for another 3 hours and then quenched by pouring the reaction mixture onto a sulfuric acid solution (10%) on crushed ice. The organic layer was separated, washed with sodium carbonate solution, and distilled to provide ( l-isopropyl-2 , -dimethyl-cyclohex-3-enyl) - methanol.

Example 5: Preparation of 4-Isopropyl-l , 5-Dimethyl-2-Oxa- Bicyclo[2.2.2] Octane (Formula Ila)

(1-isopropyl-2,4-dimethyl- 4-isopropyl-1 ,5-dimethyl-2 cyclohex-3-enyl)-methanol -oxa-bicyclo[2.2,2]octane

[0045] (l-Isopropyl-2, 4-dimethyl-cyclohex-3-enyl) -methanol (165 g, 0.9 mol, obtained in Example 4) was dissolved in toluene with methanesulfonic acid (MSA, 5 g, 0.05 mol). The resulting solution was heated to 70°C and aged at 70°C for 2 hours. GC analysis showed the completion of cyclization. The reaction mixture was cooled to room temperature, washed with sodium carbonate solution, and distilled to provide 4- isopropyl-1 , 5-dimethyl-2-oxa-bicyclo [2.2.2] octane .

4-Isopropyl-l, 5-dimethyl-2-oxa-bicyclo [2.2.2] octane was described as having herbal, camphor, woody, minty, and patchouli aspects.

Example 6: Preparation of 3 , 4-Dimethyl-2-Methylene-Pentanal

3,4-dimethyl-pentanal 3,4-dimethyl-2-methylene-pentanal

[0046] Dibutylamine (34 g) , acetic acid (15.78 g) , and formaldehyde (230 g) were charged to a reaction flask and heated to 70°C. 3 , 4-Dimethyl-pentanal (500 g) was fed over 2 hours and aged for another hour. The reaction mixture was cooled down and toluene (200 mL) was added. The reaction mixture was sequentially washed with water (2 L) , sodium carbonate solution (1 L) , and brine (1 L) to provide the crude product 3 , 4-dimethyl-2-methylene-pentanal .

Example 7: Preparation of 1- (1 , 2-Dimethyl-Propyl) -3-Methyl- Cyclohex-3-Enecarbaldehyde

1-(1 ,2-dimethyl-propyl)-4-methyl

3,4-dimethyl-2-methylene-pentanal

-cyclohex-3-enecarbaldehyde

[0047] 3, 4-Dimethyl-2-methylene-pentanal (550 g, obtained in Example 6) and 393g of isoprene were charged to a Parr Bomb, heated to 160 °C, and aged for 12 hours. The rushed over material provided ~32% recovery of 1- (1, 2-dimethyl- propyl) -4-methyl-cyclohex-3-enecarbaldehyde (415 g) .

Example 8: Preparation of [1- (1 , 2-Dimethyl-Propyl) -4- Methyl-Cyclohex-3-Enyl] -Methanol

1 -(1 ,2-dimethyl-propyl)-4-methyl [1 -(1 ,2-dimethyl-propyl)-4-methyl -cyclohex-3-enecarbaldehyde -cyclohex-3-enyl]-methanol

[0048] 1- ( 1, 2-Dimethyl-propyl) -4-methyl-cyclohex-3- enecarbaldehyde (415 g, obtained in Example 7) and methanol (300 mL) were charged into a reaction flask. Sodium borohydride (15 g) was added slowly and the temperature was kept at 35 °C with an ice bath. The reaction mixture was aged for 2 hours and quenched onto HC1 (42 g) and ice and extracted with toluene. The reaction mixture was washed until neutral. The rushed over material provided the recovery of [1- (1, 2-dimethyl-propyl) -4-methyl-cyclohex-3- enyl] -methanol (366 g) .

Example 9: Preparation of 4- (1 , 2-Dimethyl-Propyl) -1-Methyl- 2-Oxa-Bicyclo [2.2.2]Octane (Formula lib):

[1 -(1 ,2-dimethyl-propyl)- -methyl 4-(1 ,2-dimethyl-propyl)-1 -methyl

-cyclohex-3-enyl]-methanol -2-oxa-bicyclo[2.2.2]octane

[0049] [1- (1, 2-Dimethyl-propyl) -4-methyl-cyclohex-3-enyl] - methanol (268 g, obtained in Example 8), MSA (10 g) , and toluene (300 mL) were charged to a 2 L reaction flask, heated to 60 °C, and aged for 12 hours. The reaction mixture was cooled, washed with saturated sodium carbonate solution, and distilled to provide 4- (1, 2-dimethyl-propyl) - l-methyl-2-oxa-bicyclo [2.2.2] octane (146 g) . 4-(l,2-

Dimethyl-propyl) -l-methyl-2-oxa-bicyclo [2.2.2] octane was described as having woody, anisic, green, powdery, and fruity notes.

Example 10: Preparation of 2- [3-Methyl-Butylidene] - Cyclopentanone

2-[3-methyl-butylidene] cyclopentanone

-cyclopentanone

[0050] Water (1.9 L) and sodium hydroxide (NaOH, 40 g, 50% caustic) were charged in a flask and heated to 80°C. A cyclopentanone 10 mol] and isovaleraldehyde (1.05 Kg, 12 mol) was slowly fed for over 5 hours. The reaction mixture was aged at 80°C for another 30 minutes, cooled to room temperature, and quenched with acetic acid (120 g, 2 mol) . A rushover process provided the crude product 2- [3-methyl-butylidene] -cyclopentanone .

Example 11: Preparation of 2- (3-Me hyl-Butyl) -Cyclopent-2- Enone

2-[3-methyl-butylidene] 2-(3-methyl-butyl)- -cyclopentanone cyclopent-2-enone

[0051] 2- (3-Methyl-butyllidene) -cyclopentanone (1.093 Kg, 7.19 mol, obtained in Example 10), acetic anhydride (300 mL, 3.17 mol), p-toluenesulfonic acid (PTSA, 10 g) , and toluene (500 mL) were charged into a flask and heated to 120-130°C. When gas chromatography analysis indicated the completion of the reaction, the reaction mixture was cooled to room temperature and quenched with Na ₂ C0 ₃ solution (100 mL) . The resulting mixture was washed twice with brine (1 L) . A rushover process provided the crude product 2- (3- methyl-butyl) -cyclopent-2-enone . Example 12 : Preparation of 2- (3-Methyl-Butyl) -3-Vinyl- Cyclopentanone (Formula III)

2-(3-methyl-butyl)- 2-(3-methyl-butyl)-3- cyclopent-2-enone vinyl-cyclopentanone

[0052] Vinylmagnesium chloride (H ₂ CHCClMg, 1 L) and cuprous chloride were charged to a dried flask under nitrogen and cooled to -25°C with a dry ice bath. The resulting mixture was fed with 2- (3-methyl-butyl) -cyclopent-2-enone (226 g, 1.49 mol, obtained in Example 11) slowly for over 4 hours, aged for another 4 hours, and allowed to warm to 0°C. The reaction mixture was then poured into acetic acid solution and washed to neutral with saturated Na ₂ C0 ₃ solution. The distillation process provided the product 2- (3-methyl- butyl) -3-vinyl-cyclopentanone . 2- (3-Methyl-butyl) -3-vinyl- cyclopentanone was described as having lactonic, peach, buttery, floral, fruity, marigold, green, herbaceous, and minty notes.

Example 13 : Preparation 2 , 5 , 5-Trimethyl-2-Propyl- [l,3]Dioxane (Formula IV) :

- _ ,. , .„ .. , 2,5,5-trimethyl-2-propyl

2,2-dimethyl-propane-1 _> 3-diol -[1 ,3]dioxane

[0053] 2-Pentanone, 2 , 2-dimethyl-propane-l, 3-diol, and a catalytic amount of p-toluenesulfonic acid (PTSA) were refluxed in toluene to provide a crude product. Distillation provided the product 2, 5, 5-trimethyl-2-propyl- [1, 3] dioxane. ¹ HNMR: 3.54 ppm (d, 2H, J=ll.l Hz), 3.44 ppm (d, 2H, J=10.7Hz), 1.67 ppm (m, 2H) , 1.44 ppm (m, 2H) , 1.35 ppm (s, 3H) , 1.00 ppm (s, 3H) , 0.93 ppm (t, 3H, J=7.4Hz), 0.90 ppm (s, 3H) . 2, 5, 5-Trimethyl-2-propyl- [1, 3] dioxane was described as having fruity and anise notes.

Example 14: Preparation of 1 , 2 , 4-Trimethyl-

Bicyclo [2.2.1] He tane-2-Carboxylic Aci

fenchol 1,2,4-trimethyl-bicyclo[2.2.1]

heptane-2-carboxylic acid

[0054] A solution of fenchol (179 g) in formic acid (90%, 157 g) was added to sulfuric acid (98%) at 0-15°C with slow stirring. Upon finish, the reaction mixture was stirred for another 2 hours and then poured into ice. The reaction mixture was extracted three times with toluene (100 mL) . The organic phases were combined and extracted with aqueous sodium hydroxide (10%, 500 mL) . The organic phase was discarded. The aqueous phase was acidified with sulfuric acid till pH<l, and then extracted with toluene. The resulting organic phase was concentrated to provide 1,2,4- trimethyl-bicyclo [2.2.1] heptane-2-carboxylic acid (135 g, 73% yield) as a white solid.

Example 15: Preparation of 1 , 2 , 4-Trimethyl-

Bicyclo[2.2.1]Heptane-2-Carboxylic Acid Methyl Ester (Formula V)

1 ,2,4-trimethyl-bicyclo[2.2.1] 1 ,2,4-trimethyl-bicyclo[2.2.1]heptane heptane-2-carboxylic acid -2-carboxylic acid methyl ester

[0055] 1,2, 4-Trimethyl-bicyclo [2.2.1] heptane-2-carboxylic acid (obtained in Example 14) was dissolved in methylene chloride (50 mL) , and added dropwise to thionyl chloride (100 mL) at 50°C. After 1 hour, excessive thionyl chloride was distilled out and methanol (100 mL) was added. The reaction mixture was stirred overnight and then poured into saturated aqueous sodium bicarbonate. The resulting mixture was extracted with toluene and the organic phase was distilled to provide 1, 2, 4-trimethyl-bicyclo [2.2.1] heptane- 2-carboxylic acid methyl ester (65 g, 45% yield). 1,2,4- Trimethyl-bicyclo [2.2.1] heptane-2-carboxylic acid methyl ester was described as having woody, pine, camphor, herbal, and earthy notes.

Example 16: Preparation of 8-Hydroxy-2 , 6-Dimethyl-Nona-2 , 6- Diene

[0056] Methyl lithium in tetrahydrofuran (THF) (1.6 L, 1 M) was charged to a flame dried 3 L reaction flask equipped with a thermometer, a mechanical stirrer, condenser, and an addition funnel. Citral was added dropwise for over 2-2.5 hours. The reaction mixture was aged until the conversion rate was greater than 90%. The reaction mixture was cooled to lower than 30 °C and quenched by the slow addition of HCl (pH < 5. 10%) . The aqueous phase was extracted three times with toluene (100 mL) and the extracts were added to the crude reaction mixture. The crude reaction mixture was then washed with saturated sodium bicarbonate (500 mL) followed by saturated salt solution and dried over anhydrous sodium sulphate. The crude reaction mixture was concentrated. The solvents were recovered via a rotary evaporator to provide 8-hydroxy-2, 6-dimethyl-nona-2, 6-diene.

Example 17: Preparation of 8-Ethoxy-2 , 6-Dimethyl-Nona-2 , 6- Diene (Formula VI)

[0057] THF (500 mL) and sodium hydride (60%, 52 g, 1.3 mol) were charged to a flame dried 2 L reaction flask equipped with a thermometer, a mechanical stirrer, a condenser, and an addition funnel. 8-Hydroxy-2 , 6-dimethyl-nona-2 , 6-diene

(obtained in Example 16) was added dropwise while allowing the temperature to rise no higher than 50 °C. After the addition was completed, the reaction mixture was aged for 1 hour. Ethyl bromide (142 g, 1.3 mol.) was added dropwise for over 2 hours. The reaction mixture was then heated to 60 °C and aged until the conversion rate was shown to be over 90%. The reaction mixture was cooled to lower than 30 °C and quenched by the slow addition of HC1 (pH < 5, 10%) . The layers were split. The aqueous phase was extracted three times with toluene (100 mL) . The extracts were added to the crude reaction mixture, which was then washed with saturated sodium bicarbonate followed by saturated salt solution and dried over anhydrous sodium sulphate. The crude reaction mixture was concentrated. The solvents were recovered via a rotary evaporator. Fractional distillation provided the compound 8-ethoxy-2 , 6-dimethyl-nona-2 , 6-dien with a boiling point of 125°C at a pressure of 4.5 mmHg. ^NMR: 5.06-5.13 ppm (m, 2H) ; 4.09-4.18 ppm (m, 1H) ; 3.43- 3.53 ppm (m, 1H) ; 3.27-3.37 ppm (m, 1H) ; 2.00-2.16 ppm (m, 4H) ; 1.60-1.74 ppm (m, 9H) ; 1.15-1.20 ppm (m, 6H) . 8- Ethoxy-2, 6-dimethyl-nona-2, 6-dien was described as having fresh, grapefruit, citrus, lemonuile, lemonalva with pamplemouse-like odor.

Example 18: Preparation of 2 , 6-Dimethyl-2- (2-Me hyl-Allyl) - Cyclohexanone

2 ,6-d imethyl- 2 ,6-dimethyl-2-(2-methyl cyclohexanone -allyl)-cyclohexanone

[0058] 2, 6-Dimethyl-cyclohexanone (1 kg, 4 mol) , trimethyl orthoformate (TMOF, 880 g) , and methanol (800 mL) were charged to a 5 L reaction flask. HC1 was added quickly.

Reaction exothermed and the temperature increased from 14 °C to 20 °C. The reaction mixture was heated to 60 °C and aged for 7 hours. When the reaction was about 75% complete, the reaction mixture was quenched with NaOCH ₃ (25%, 25 g) , heated to 90 °C, and applied to a Bidwell-Sterling trap. The reaction mixture was then cooled to room temperature followed by sequential addition of methallyl alcohol (1.25

Kg, 8.5 moles), HOAc (50 g) , and methane sulfonic acid

(MSA, 10 g) . The resulting mixture was heated to 110°C, applied to a Bidwell-Sterling trap, and aged for 4 hours until gas chromatograph analysis indicated that the reaction was 95% completed. The reaction mixture was then cooled and washed with saturated sodium carbonate solution

(3 L) to provide the crude product 2 , 6-dimethyl-2- (2- methyl-allyl) -cyclohexanone .

Example 19: Preparation of 2 , 2 , 3a, 7-Tetramethyl-Octahydro- Benzofuran (Formula Vila)

2 ,6-d imethyl-2-(2-methyl 2,2,3a,7-tetramethyl- -allyl)-cyclohexanone octahydro-benzofuran

[0059] A 3 L reaction flask was charged with vitride (325 g, 0.9 mol) and toluene (500 mL) , heated to 100°C, fed with 2, 6-dimethyl-2- (2-methyl-allyl) -cyclohexanone (200 g, 1.1 mol, obtained in Example 18) for over 2 hours, and aged for another 2 hours. After the reaction completed, the reaction mixture was cooled to room temperature, quenched with IPA (100 mL) . NaOH (50%, 300 g) and water (200 mL) were then added, heated to 80 °C, and aged for another hour. The reaction mixture was cooled to room temperature and more water (200 mL) was added. Layers were split to dispose the aqueous waste. The organic layer was charged back to the flask. Toluene (300 mL) was added and water was removed with a Bidwell-Sterling trap through azeotrope. The resuling mixture was cooled to 50 °C. MSA (28 g, 0.3 mol) was added and the reaction mixture was heated to reflux. The consumption of the starting material was indicated after 3 hours. The resulting mixture was then cooled to room temperature and washed with saturated sodium carbonate solution (1 L) followed by brine (1 L) . Distillation and fractionation provided the product 2 , 2 , 3a, 7-tetramethyl- octahydro-benzofuran (125 g) . 2 , 2 , 3a, 7-Tetramethyl- octahydro-benzofuran was described as having herbal, sweet, camphor, woody, fresh, and green notes.

Example 20: Preparation of 3a-Isopropyl-2 , 6-Dimethyl- Octahydro-Benzofuran (Formula Vllb) [0060] Menthone (500 g) , trimethylorthoformate (377 g) and methanol (400 mL) were charged to a 3 L reaction flask. In one portion, hydrochlorioc acid (3 g) was added and the mixture exothermed from 22 °C to 40 °C. The reaction mixture was aged 6 hours and quenched with sodium methoxide solution (35 g) . Low boiling materials were removed while the reaction mixture was heated to 90°C. Allyl alcohol (404 g) and acetic acid (195 g) were added and the reaction mixture was heated to 160 °C. The reaction mixture was held at 160 °C for 3 hours, cooled to 25 °C, and washed with brine

(500 mL) . The crude product was distilled to provide a mixture of allyl menthone isomers .

[0061] Red-Al® (397 g) was charged to a 2 L reaction flask and heated to 55 °C. Allyl menthone isomers (248 g, obtained in above) were fed into the flask and the reaction was allowed to exotherm to 70 °C. The reaction mixture was aged for 8 hours and quenched with isopropanol (100 mL) followed by aqueous sodium hydroxide solution (50%, 307 g) . The resulting organic layer was washed with brine (500 mL) . The crude alcohol was distilled to provide a mixture of allyl menthol isomers.

[0062] Allyl menthol isomers (200 g, obtained in above) , toluene (500 mL) , and methanesulfonic acid (MSA, 5 g) were charged to 1 L reaction flask. The reaction mixture was heated to 80°C, aged for 8 hours, then cooled to 22°C, and washed with aqueous sodium carbonate solution (10%, 300 mL) . The resulting crude mixture was purified by distillation to afford 3a-isopropyl-2 , 6-dimethyl-octahydro- benzofuran. 3a-Isopropyl-2 , 6-dimethyl-octahydro-benzofuran was described as having cedar wood, green, spice, flora, eucalyptus, and slight piney notes. Example 21: Preparation of 4-Cyclopropylmethoxymethyl-5- Methyl-Cyclohexene (Formula VIII)

4-cyclopropylmethoxymethyl

(6-methyl-cyclohex- -5-methyl-cyclohexene

3-enyl)-methanol

[0063] A reaction flask was charged with tetrahydrofuran (THF, 500 mL) and sodium amide (NaNH ₂ , 100 g, 2.6 mol) and heated to reflux (~65°C). ( 6- ethyl-cyclohex-3-enyl ) - methanol (300 g, 2.3 mol) was fed in. The reaction mixture was aged for a half-hour. Bromomethyl-cyclopropane (526 g, 3.9 mol) was then fed for over 2 hours at the reflux temperature. The reaction was monitored by gas chromatography. A sample the reaction mixture was quenched in isopropyl alcohol, water, and toluene. After the feed of bromomethyl-cyclopropane was completed, the reaction was aged for a total of 6 hours . The reaction mixture was then cooled to 10 °C and quenched with isopropyl alcohol (100 mL) , water (1 L) , and toluene (500 mL) . On the work-up, the reaction mixture was acidified with HC1 (300 mL) and washed with sodium carbonate solution (5%, 500 mL) in a separatory funnel followed with warm H ₂ 0 until the pH was neutral. Distillation of the resulting mixture provided the product 4-cyclopropylmethoxymethyl-5-methyl-cyclohexene . 4- Cyclopropylmethoxymethyl-5-methyl-cyclohexene was described as having fruity and green notes.

Example 22: Preparation of Cyclopropanecarboxylic Acid 1- Methyl-Hexyl Ester (Formula IX)

[0064] 2-Heptanol (200 g, 1.72 mol) and cyclopropanecarboxylic acid (163 g, 1.90 mol) were added into toluene (500 mL) , followed by p-toluenesulfonic acid (3.2 g, 0.0172 mol) . The reaction mixture was heated to reflux for 6 hours, cooled to room temperature, and quenched with aqueous sodium bicarbonate (1 L) . The reaction mixture was then washed with brine (0.5 L) and dried over sodium sulfate (50 g) . The solvent was removed and the reaction mixture was distilled to provide _, the product cyclopropanecarboxylic acid 1-methyl-hexyl ester (253 g) . Cyclopropanecarboxylic acid 1-methyl-hexyl ester was described as having fruity, herbal, seaweed, chamomile, and ambrette seed notes.

Example 23: Preparation of 3-Isopropenyl-6-Methyl-2- Propenyl-Tetrahydro-Pyran (Formula X) :

6-methyl-hept 3-isopropenyl-6-methyl-2- crotonaldehyde

-5-en-2-oI propenyl-tetrahydro-pyran

[0065] 6-Methyl-hept-5-en-2-ol (512 g, 3.8 mol, 96%), toluene (750 ml), and p-toluenesulfonic acid (pTSA, 2.6 g) were charged in a flask and heated to 122 °C. Crotonaldehyde

(350 g, 5 mol) was fed into the mixture for over 3-4 hours at reflux. Water was removed with a Bidwell-Sterling trap. The reaction mixture was aged for l.hour. Standard addition and gas chromatography (GC) analysis indicated that about 11% of the starting material 6-methyl-hept-5-en-2-ol was left. Additional crotonaldehyde (35 g, 0.5 mol) was added. The reaction mixture was at reflux for another 45 minutes. About 70 ml water was collected and the final temperature was about 118 °C. GC analysis indicated that about 8% of the starting material 6-methyl-hept-5-en-2-ol was left. The reaction mixture was quenched with water and wash one time with dilute carbonate solution. The consequent rush-over process provided the product 3-isopropenyl-6-methyl-2- propenyl-tetrahydro-pyran (493 g) with a boiling point of 109°C at a pressure of 25 mmHg. 3-Isopropenyl-6-methyl-2- propenyl-tetrahydro-pyran was described as having woody, fresh, cinnamon, and spicy notes.

Example 24: Preparation of Acetic Acid 3-Isopropyl-l , 2- Dimethyl-Cyclopentyl Ester (Formula XI)

[0066] Trans-dihydroplinol (165 g) and dimethylaminopyridine (2 g) were charged into a 1 L round bottom flask and heated to 80 °C. Acetic anhydride (143 g) was added to the resulting mixture and was stirred at the same temperature until the majority of the starting material was consumed. The reaction mixture was then cooled to room temperature, washed with water and sodium carbonate, and extracted with toluene. The organic solvents were removed in vacuo and fractional distillation provided the product acetic acid 3-isopropyl-l, 2-dimethyl- cyclopentyl ester (45 g, 21% yield) . Acetic acid 3- isopropyl-1, 2-dimethyl-cyclopentyl ester was described as having woody, fresh, cinnamon, and spicy notes.

Example 25: Preparation of 4- (2 , 4-Dimethyl-Cyclohex-3- Enylidene) -Butan-2-One (Formula XII)

[0067] Ketoester (780 g) was added into a 2 L round bottom flask and heated to 200°C. Water (2 equivalents) was added drop-wise and the lighter solvent was removed via a Bidwell-Sterling trap. The reaction mixture was then cooled to room temperature. The crude product was dried over anhydrous sodium sulfate. Fractional distillation provided product 4- (2, 4-dimethyl-cyclohex-3-enylidene) -butan-2-one (231 g) . 4- (2 , 4-Dimethyl-cyclohex-3-enylidene) -butan-2-one was described as having strong woody and spicy characteristics .

Example 26: Preparation of 4-Methyl-Cyclohex-4-Ene- Dicarboxylic Acid Dimethyl Ester

isoprene dimethyl maleate 4-methyl-cyclohex- -ene-1 ,2- dicarboxylic acid dimethyl ester

[0068] Isoprene (350 g, 5.1 mol) and dimethyl maleate (741 g, 5.1 mol) were loaded into a stainless steel autoclave. The autoclave was sealed and heated to 150 °C. The temperature of the autoclave increased to 195 °C due to the heat of the reaction. The temperature was held at 160 °C for 1 hour. Gas chromatography (GC) analysis indicated the completion of the reaction. The auto ^' clave was then cooled to room temperature. Simple distillation of the resulting mixture provided 4-methyl-cyclohex-4-ene-l , 2-dicarboxylic acid dimethyl ester (725 g, 3.4 mol, 66% yield) as a light yellow liquid.

Example 27: Preparation of 2- [6- (1-Hydroxy-1-Methyl-Ethyl) - 4-Methyl-Cyclohex-3-Enyl] -Propan-2-Ol

4-methyl-cyclohex-4-ene-1 ,2- 2-[6-(1 -hydroxy-1 -methyl-ethyl)-4- dicarboxylic acid dimethyl ester methyl-cyclohex-3-enyl]-propan-2-ol

[0069] ethylmagnesium chloride (MeMgCl, 3 M, 4.6 L, 13.6 mol) and tetrahydrofuran (THF, 2.5 L) were placed in a 12 L round bottom flask under nitrogen. The resulting solution was cooled to 0-10 °C using an automatic dry ice bath. The 4-methyl-cyclohex-4-ene-l, 2-dicarboxylic acid dimethyl ester (725 g, 3.4 mol, obtained in Example 26) was then fed into the reaction flask under nitrogen while the temperature was held steady. The completion of the reaction was monitored by GC analysis. After the feed was complete, the reaction mixture was quenched by pouring onto sulfuric acid solution (10%) and ice. The resulting layers were then split and the organic layers were washed with saturated sodium carbonate solution. The resulting mixture was then reduced in volume using a rotovap to provide the crude product 2- [6- (1-hydroxy-l-methyl-ethyl) -4-methyl-cyclohex- 3-enyl] -propan-2-ol (720 g, 3.3 mol).

Example 28: Preparation of 1 , 1 , 3 , 3 , 5-Pentamethy1- 1 , 3 , 3 4 , 7 , 7a-Hexahydro-Isobenzofuran (Formula XIII)

2-[6-( 1 -hydroxy-1 -methyl-ethyl)-4- 1 ,1 ,3,3,5-pentamethyM ,3,3a,4,7,7a methyl-cyclohex-3-enyl]-propan-2-ol -hexahydro-isobenzofuran [0070] 2- [6- (1-Hydroxy-l-methyl-ethyl) -4-methyl-cyclohex-3- enyl] -propan-2-ol (720 g, 3.3 mol, obtained in Example 27) was loaded into a round bottom flask fitted with a Bidwell- Sterling trap and dissolved in toluene (1 L) . An acid catalyst p-toluenesulfonic acid (pTSA, 40 g, 0.18 mol) was added and the mixture was heated to reflux. The reflux was maintained for 1.5 hours. Water was collected in the Bidwell-Sterling trap during this period. GC analysis indicated the completion of the reaction. The resulting mixture was reduced in volume and purified by fractional distillation to provide 1, 1, 3, 3, 5-pentamethyl-

1, 3, 3a, 4 , 7 , 7a-hexahydro-isobenzofuran (60 g, 9% yield). 1,1,3, 3, 5-Pentamethyl-l, 3, 3a, 4,7, 7a-hexahydro-isobenzofuran was described as having woody, camphor, fresh and mushroom notes.

Exam le 29: Preparation of Undec-8-Ene-2 , 5-Diol

but-3-yn-2-ol hept-4-enal undec-8-en-3-yne-2,5-diol

[0071] But-3-yn-2-ol was added into a solution of ethyl maganesium bromide (EtMgBr) in tetrahydrofuran (THF) . Hept- 4-enal was then dropped into the mixture at room temperature and aged for 2 hours. The rush over process provided the product undec-8-en-3-yne-2 , 5-diol .

undec-8-en-3-yne-2, 5-diol undec-8-ene-2, 5-diol [0072] Undec-8-en-3-yne-2, 5-diol (obtained in Example 29) was hydrogenated under hydrogen and 10 percent palladium on barium sulphate and quinoline. The rush over process provided the product undec-8-ene-2 , 5-diol .

Example 31: Preparation of 2- (Hex-3-Enyl) -5-Methyl- Tetrahydro-Furan (Formula XIV) undec-8-ene-2, 5-diol 2-(hex-3-enyl)-5-methyl-tetrahydro-furan

[0073] Undec-8-ene-2, 5-diol (obtained in Example 30) was heated to 150 °C with KHSO ₄ . The resulting mixture was distilled to provide the product 2- (hex-3-enyl) -5-methyl- tetrahydro-furan . 2- (Hex-3-enyl) -5-methyl-tetrahydro-furan was described as having floral and vegetable notes.