Abstract:
The present invention relates to novel compounds useful as fragrance materials which have the structure ##STR1## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond; R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl; and X is halogen. The invention also provides methods of preparing these compounds from readily available cyclohexene derivatives and fragrance compositions which include the compounds.

Description:
This is a division of application Ser. No. 129,898, filed Mar. 13, 1980, now U.S. Pat. No. 4,272,412. 
    
    
     BACKGROUND OF THE INVENTION 
     There is an increased demand for materials which can be used to modify and/or enhance the organoleptic properties of consumable items. The natural oils which have traditionally been used for this purpose often suffer the disadvantages of irregular or limited supply, variable quality and high cost. Consequently the search for new and inexpensive chemicals which can be used as partial or total replacements for essential oils, or which can be used in the creation of new and unique flavor and fragrance materials has intensified in recent years. 
     The use of halogen containing compounds as fragrance materials is well documented. One example is gamma homocyclogeranyl chloride which has the general structure ##STR2## and is a component of tincture of Ambergris. 2-Chloro-3-methoxy-5-methylphenol and 2,4-dimethoxy-6-methyl chlorobenzene have been found in Evernia Prunastri. Further examples may be found in Actander, Perfume and Flavor Chemicals (1969). For example alphabromostyrol which has the structure ##STR3## is identified as compound No. 370 in Actander. Its fragrance is described therein as pungent-sweet, grassy-floral odor, reminiscent of Hyacinth in extreme dilution. Slightly softer than the odor of omega-Bromostyrol. 
     Actander compound No. 608 is 2-chloro-4,6-dinitro-1,3-dimethyl-5-tertiary-butylbenzene which has the structure ##STR4## and is described as having an odor similar to 2,4,6-trinitro-3-tertiary-butyl toluene, sweet, heavy, musky, slightly more pungent and less tenacious. 
     Actander compound No. 2272 is mononitro dibromobutylmeta-cresol methylether which has the structure ##STR5## and is described as having a sweet Ambergris musk-like odor of good tenacity. 
     SUMMARY OF THE INVENTION 
     In accordance with the present invention it has been found that compounds having the structure ##STR6## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond; R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl, and X represents a halogen group are useful as fragrance materials. 
     The present invention also provides efficient and economical processes for preparing these compounds involving reacting a substituted cyclohexene derivative having the structure ##STR7## wherein the dashed line may be either a carbon-carbon single bond or a carbon carbon double bond and R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl with a hypohalous acid having the formula HO-X wherein X is halogen. 
     Finally in accordance with the present invention it has been found that fragrance compositions can be prepared by incorporating in these compositions the novel compounds of this invention. 
     DETAILED DESCRIPTION OF THE INVENTION 
     In accordance with this invention, there have been discovered novel halogen-containing cyclohexane derivatives as represented by the structure ##STR8## wherein the dashed line may either be a carbon-carbon single bond or a carbon-carbon double bond; R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl; and X represents a halogen group have been prepared. It will be recognized that the chemicals of this invention can exist in several stereoisomeric forms. The foregoing structural formula is intended to embrace the individual stereoisomers, as well as mixtures of the various stereoisomers of the halogen compounds of this invention. The compounds exhibit clean, soft, powdery, warm, sweet, woody orris, berry-like notes rendering them useful in fine fragrances as well as perfumed products such as deodorants, cosmetic preparations and the like. 
     The compounds of this invention can be conveniently and inexpensively prepared by reacting a cyclohexene derivative having the structure ##STR9## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond and R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl with a hypohalous acid having the general formula HO-X, where X is selected from a group consisting of the halogens chlorine, bromine or iodine, preferably chlorine or bromine in the presence of an organic solvent such as methylene dichloride, ethylene dichloride, hexane or toluene, preferably methylene dichloride or ethylene dichloride. The hypohalous acid is generated in situ in accordance with standard procedures (see H. O. House, &#34;Modern Synthetic Reactions,&#34; 2nd ed., p. 434 (1972). Isolation and purification of the final products is achieved by conventional techniques including extraction, distillation, preparative chromatographic techniques and the like. 
     One or more of the halogen-containing cyclohexane derivatives of this invention and auxiliary perfume ingredients, for example, alcohols, aldehydes, ketones, nitriles, esters and essential oils may be admixed so that the combined odors of the individual components produce a desired fragrance. Such perfume compositions are carefully balanced, harmonious blends of essential oils, aroma chemicals, resinoids and other extracts of natural odorous materials. Each ingredient imparts its own characteristic effect to the composition. Thus, one or more of the halogen-containing compounds of this invention can be employed to impart novel characteristics into fragrance compositions. 
     Such compositions may contain up to about 80 weight percent of any one or more of the halogen containing cyclohexane derivatives of the invention. Ordinarily at least 0.001 weight percent of the halogen-containing cyclohexane derivative is required to impart significant odor characteristics. Amounts in the range of from about 1 to about 60 weight percent are preferred. The halogen-containing compounds of this invention may be formulated into concentrates containing about 1 to 60 weight percent of the chemical in an appropriate solvent. Such concentrates are then employed to formulate products such as colognes, deodorants, etc., wherein the concentration of the chemicals of this invention can be in the range of from about 0.001 to about 7 weight percent depending upon the final product. 
     A number of examples are provided hereinafter to illustrate the preferred embodiments of this invention, but are in no way meant to limit the scope thereof. 
     The following instrumentation was used to characterize the novel compounds of this invention. Nuclear Magnetic Resonance (NMR) spectra were recorded with a Varian Associates T-60A spectrometer using tetramethylsilane as the internal reference. Infrared (IR) spectra were obtained with a Perkin Elmer 710 B spectrophotometer. Mass spectra (MS) were obtained with a Hewlett-Packard 5985 Mass Spectrometer. Unless otherwise stated weights are in grams, temperatures are in degrees centigrade and pressures in mm Hg. 
    
    
     EXAMPLE 1 ##STR10## 
     To a mixture of commercial bleach (28.5 ml of a 5.25% solution of sodium hypochlorite) α-dihydro-ionone (3.88 g) and methylene chloride (110 ml) was added a solution of potassium phosphate (monobasic) (5.44 g) in water (40 ml) during a 15 minute period. The mixture was stirred for 1 hour at 25°. The methylene chloride solution was washed with sodium bicarbonate solution, the solvent evaporated, and the residue distilled to give 2.81 g (61% yield) of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl)-2-butanone, bp 101°-106°, 0.2 mm. NMR (CDCl 3 ) δ0.85 and 0.95 (6H, 2s, &gt;C(CH 3 ) 2 ), 0.9-2.6 (9H, m), 2.10 (3H, s, --COCH 3 ), 4.36-4.55 (1H, t, J=6 Hz, &gt;CHCl), 4.76 and 5.33 (2H, 2s, &gt;C=(CH 2 ). IR (film) γmax 2950, 1720, 1675, 1650, 1455, 1360. MS m/e 193, 175, 159, 134, 119. 
     EXAMPLE 2 
     The reaction of α-dihydro-ionone and hypochlorous acid was carried out as described in Example 1 except that hexane was substituted for methylene chloride. A 59% yield of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl-2-butanone was obtained. The spectral data was identical to that reported in Example 1. 
     EXAMPLE 3 ##STR11## 
     A solution of sodium bromide (6.17 g) in water (10 ml) and commercial bleach (31.2 ml of a solution of sodium hypochlorite) were stirred together for 5 minutes and a solution of dihydro-α-ionone (3.88 g) in methylene chloride was added. Then a solution of potassium phosphate (monobasic) (5.44 g) in water (30 ml) was added during 30 minutes. After stirring for 50 minutes at 25° a solution of sodium bromide (2.05 g) and commercial bleach (10 ml) was added, followed by a solution of potassium phosphate (monobasic) (2.72 g) in water (10 ml) and the reaction mixture stirred for 15 minutes at 25°. The methylene chloride solution was washed with sodium bicarbonate solution and the solvent evaporated to provide the crude product (5.86 g). Column chromatography gave 1.87 g of 4-(5-bromo-6-methylene-2,2-dimethylcyclohexyl)-2-butanone. NMR (CDCl 3 ) δ0.93 (6H, s, &gt;C(CH 3 ) 2 ), 0.9-2.6 (9H, m), 2.12 (3H, s, --COCH 3 ), 4.6-5.1 (1H, m, &gt;CHBr), 4.76 and 5.28 (2H, 2s, &gt;C═CH 2 ), 4.68 and 5.20 (2H, 2s, &gt;C═CH 2 , minor isomer; isomer ratio 3/1). IR (film) ν max  2960, 1720, 1675, 1650, 1455, 1360. 
     EXAMPLE 4 ##STR12## 
     To a mixture of commercial bleach (42.6 ml of a 5.25% solution of sodium hypochlorite), α-irone (6.24 g), and methylene chloride (200 ml) was added a solution of potassium phosphate (monobasic) (8.16 g) in water (40 ml) during a 30 minute period. The mixture was stirred for 1 hour at 25°. The methylene chloride solution was washed with sodium bicarbonate solution and evaporated to give 7.8 g of crude product. Purification by column chromatography gave 4.59 g of 4-(5-chloro-6-methylene-2,2,3-trimethylcyclohexyl)-3-buten-2-one. NMR (CDCl 3 ) δ0.70-0.78 (2H, d, J=5 Hz, &gt;CHCH 3 ), 0.90, 0.93 and 0.99 (6H, 3s, &gt;C(CH 3 ) 2 ), 0.9-1.3 (1H, m, &gt;CHCH 3 ), 1.5-2.1 (2H, m, --CH 2  --), 2.25, 2.26 and 2.28 (3H, 3s, --COCH 3 ), 2.67 and 2.83 (1H, 2s, &gt;CH--CH═CH--), 4.6-4.9 (1H, m, &gt;CHCl), 4.93 and 5.12 (2H, 2s, &gt;C═CH 2 , 5.8-6.3 (1H, m, --CH═CH--CO--), 6.6-7.6 (1H, m, --CH═CHCO--). IR (film) ν max  2960, 1695, 1675, 1620, 1460, 1430 cm -1 . MS m/e 207, 163. 
     EXAMPLE 5 ##STR13## 
     To a mixture of commercial bleach (28.5 ml of a 5.25% solution of sodium hypochlorite), α-ionone (3.84 g), and methylene chloride (330 ml) was added a solution of potassium phosphate (monobasic) (5.44 g) in water (40 ml) during a 30 minute period. The mixture was stirred for 30 minutes at 25°, the methylene chloride solution washed with sodium bicarbonate solution and evaporated to give 4.1 g of crude product. Purification by column chromatography gave 2.35 g of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl)-3-buten-2-one. NMR (CDCl 3 ) δ0.90 and 0.93 (6H, 2s, &gt;C(CH 3 ) 2 ), 0.9-2.1 (4H, m), 2.27 (3H, s, --COCH 3 ), 2.53 and 2.71 (1H, 2s, &gt;CH--CH═CH--), 4.35-4.68 (1H, m, &gt;CHCl), 4.70, 4.83, 5.15 and 5.33 (2H, 4s, &gt;C═CH 2 ), 5.9-6.4 (1H, m, --CH═CH--CO--), 6.7-7.3 (1H, --CH═CH--COCH 3 ). IR (film) ν max  2960, 1695, 1675, 1630, 1450, 1430 cm.sup. -1. MS m/e 191, 149. 
     EXAMPLE 6 
     The following illustrates the utility of 4-(5-chloro-6-methylene-2,2-dimethyl-1-cyclohexyl)-2-butanone, the compound of Example 1, in a fantasy floral composition. 
     
         ______________________________________FANTASY FLORALpts/wt       Component______________________________________10           Oil Patchouly10           Eugenol Extra10           Geranyl Acetate10           Anisyl Acetate20           Iso Eugenol20           Hexyl Cinnamic Aldehyde20           Hydroxy Citronellal20           Oil Ylang Extra25           1% Sol. Aldehyde C-12 MNA in        D.E.P. Odorless30           Geraniol30           Vetiveryl Acetate40           Phenyl Ethyl Alcohol50           Coumarin50           Musk Ketone50           Oil Bergamot60           Oil Lemon70           Vanillin75           Compound of Example 1100          Heliotropin Extra100          Benzyl Acetate100          Linalool100          Linalyl Acetate1000______________________________________ 
    
     EXAMPLE 7 
     The following illustrates the utility of 4-(5-bromo-6-methylene-2,2-dimethyl-1-cyclohexyl)-2-butanone, the compound of Example 3, in fragrance compositions of the fougere type. 
     
         ______________________________________FOUGEREpts/wt       Component______________________________________20           Oil Vetiver Reunion20           10% Sol. Rose Oxide in D.E.P.        Colorless20           Labdanum Resinoid Absolute30           Coumarin30           10% Sol. Aldehyde C-11 in D.E.P.        Odorless30           Oil Patchouly30           Oil Geranium Maroc30           Citronellal Extra30           Geraniol30           Iso Amyl Salicylate30           Eugenol40           Linalool FCC50           Oil Lemon50           Oil Fir Needles Canadian50           Linalyl Acetate50           Phenyl Ethyl Alcohol50           Hexyl Cinnamic Aldehyde100          Oil Lavandin Abrial Extra100          Cedryl Acetate100          Compound of Example 3110          Diethyl Phthalate1000______________________________________ 
    
     EXAMPLE 8 
     A fantasy woody floral fragrance may be prepared containing the compound of Example 4. 
     
         ______________________________________FANTASY WOODY FLORALpts/wt       Component______________________________________60           Rhodinol Extra10           Phenylethyl Phenylacetate100          Phenyl Ethyl Alcohol50           Oil Rose Bulgarian30           Oil Ylang Extra40           Jasmin Absolute60           Linalool50           Benzyl Acetate140          Oil Vetiver Reunion50           Acetyl Cedrene30           10% Aldehyde C-11 in D.E.P.        Odorless70           Musk Ketone40           Coumarin30           Amyl Cinnamic Aldehyde130          Hydroxycitronellal110          Compound of Example 41000______________________________________