-- 2,800,511 United States Patent Office Patented July 23, 1957 2

(3) C3 CEis C3 C3 2,800,511 / E. H S CHO SUBSTITUTED TETRAHYDRONAPHTHALENE -- (CH2)N --> ALDEHYDES E. R Marion S. Carpenter, Nutley, William M. Easter, Jr., \ H Hasbrouck Heights, and Thomas F. Wood, Little Falls, CH CE N. J., assignors to The Givaudan Corporation, New in which R represents a lower alkyl group. York, N. Y., a corporation of New Jersey Examples of specific compounds we have prepared in No Drawing. Application January 28, 1955, 10 clude 7-formyl 1, 14,4,6-pentamethyl 1,2,3,4-tetrahydro Seria No. 484,835 naphthalene, 7-formyl 1,1,4,4-tetramethyl 6-ethyl 1,2,3,4- tetrahydronaphthalene and 7-formyl 1, 1,4,4-tetramethyl 9 Claims. (C. 260-599) 6-isopropyl. 1,2,3,4-tetrahydronaphthalene. 5 The following examples are given in order more fully This invention relates to novel chemical compounds, to illustrate this invention, without, however, limiting the and more especially to substituted tetrahydronaphthalene same to them. aldehydes having musk-like odors. EXAMPLE 1. Most of the known synthetic musk-like compounds fall Preparation of 7-formyl 1,1,4,4,6-pentamethyl 1,2,3,4- into two classes: (1) nitrated aromatic hydrocarbons, such 20 as musk xylene, and (2) macrocyclic ketones, lactones tetrahydronaphthalene or esters, such as cyclopentadecanone, cyclopentadecanol A mixture of 275 grams of toluene and 10 grams of ide and ethylene brassylate. While members in the first aluminum chloride was cooled to 20 C. and to it was group are inexpensive to manufacture, they suffer from added a solution of 183 grams of 2,5-dichloro 2,5-dimeth the disadvantage that they are not light-stable or alkali ylhexane in 185 grams of toluene during 45 minutes, stable, frequently causing discoloration in products such keeping the temperature at 20-25 C. and agitating con as soap. Members of the second group, while reasonably tinuously. After the evolution of hydrogen chloride had stable to light and alkalies, are difficult to manufacture ceased the solution was quenched in water, washed to and are relatively costly. neutrality and distilled. There was obtained, in addition We have found that certain novel chemical compounds 30 to the excess of toluene, 197 g. of a colorless practically which we have synthesized have the desirable property of odorless oil boiling at 78 C./1.5 mm. Hg and melting at being musk-like in olfactory character and yet are extreme 29 C., which is 1,14,4,6-pentamethyl 1,2,3,4-tetrahydro ly stable to light and alkalies, and, at the same time, are naphthalene. inexpensive to manufacture and hence not relatively costly. A mixture of 202 grams of 1,1,4,4,6-pentamethyl 12, Our novel chemical compounds are lower alkyl-sub 35 3,4-tetrahydronaphthalene, 20 grams of paraformalde stituted, formyl - 1, 1,4,4-tetramethyl-1,2,3,4-tetrahydro hyde and 140 grams of 31% hydrochloric acid was agitated naphthalenes. They are soluble in benzene, ethyl alcohol, vigorously and warmed to 53° C. Then 250 grams of ethylene dichloride and similar solvents. All possess musk 93% sulfuric acid was added during 4 hours, maintaining like odors per se or in solution and all are light-stable vigorous agitation and gradually increasing the tempera and alkali-stable. 40 ture to 65° C. Agitation was continued 8 hours further in general, our novel musk-like compounds are prepared While the temperature was gradually increased to 72 C. in three steps: After cooling and settling the lower acid layer was dis (1) Condensation of 2,5-dichloro 2,5-dimethyl hexane carded, the upper oily layer was diluted with an equal with a lower alkyi-substituted benzene in the presence of volume of benzene and washed with 200 grams of water. a Suitable condensing agent Such as aluminum chloride or The benzene solution was dried over anhydrous soda ash, ferric chloride to produce a 6-alkyl. 1,1,4,4-tetramethyl filtered and distilled in the presence of 2 grams of anhy 1,2,3,4-tetrahydronaphthalene; drous soda ash, first at atmospheric pressure to remove (2) Treatment of the product of the first step with the solvent and finally in vacuo. There was collected, formaldehyde and hydrochloric acid to produce the cor in addition to 75 grams of recovered 1,14,4,6-pentamethyl responding 7-chloromethyl derivative, and 50 1,2,3,4-tetrahydronaphthalene, 104 grams of 7-chloro (3) Treatment of the product of the second step with methyl 1, 1,4,4,6-pentamethyl 1,2,3,4-tetrahydronaphtha hexamethylenetetramine to convert the chloromethyl lene as a colorless oil boiling at 131° C./2.5 mm. Hg which group to the corresponding formyl (or aldehyde) group. rapidly solidified. After crystallization from half its These reactions may be illustrated graphically by the weight of naphtha, 93 grams was obtained in the form of following equations: 55 colorless, odorless crystals melting at 89-90.5 C. A mixture of 124 grams of 7-chloromethyl 1,14,4,6- (1) CH3 CH3 pentamethyl 1,2,3,4-tetrahydronaphthalene, 70 grams of N c^ H. CH3Y CHs hexamethylenetetramine and 43 grams of water was re fluxed with vigorous agitation for 3 hours at a tempera H.c? Yol E 60 ture of 118-119 C. The viscous mixture was then Hé2 Cl -- H steam-distilled by passing through it a current of super N/ R R heated steam until the inside temperature had reached /S "e2S about 155 C., at which point all volatile material had CHs CHs CEI CEI been driven over. The crystalline portion of the distillate 65 was separated from the aqueous portion and dissolved in benzene. The benzene solution was washed with 5% sul furic acid to remove amines, then with water to neutrality and the solvent was evaporated off, leaving 63 g. of crude crystalline material. After crystallization from alcohol 70 there was obtained 47 grams of 7-formyl 1, 1,4,4,6-penta methyl 1,2,3,4-tetrahydronaphthalene as colorless crystals having a strong, musk-like odor and melting, in a capillary 2,800,511. 3 4 tube at 85-91° C. This wide range in melting point is anhydrous ferric chloride was cooled to 10° C. and to it indicative, not of an impure product but rather of a product was added a solution of 366 grams of 2,5-dichloro 2,5-di having a double melting point. Freezing point analysis methylhexane in 520 grams of cumene during 1 hour, showed the crystals to be 99-96 pure and to have a freez keeping the temperature at 10-15 C. and agitating con ing point of 92 C. The semicarbazone melted at tinuously. After the evolution of hydrogen chloride had 213.5-214.5 C, then resolidified and finally melted at ceased the solution was quenched in water, Washed to 275° C. The oxime melted at 151.5-153 C. The crystal neutrality and distilled to yield, in addition to 408 grams line aldehyde exhibits a phototropic effect, that is, the of recovered cumene, 392 grams of a colorless, practi originally colorless crystals rapidly become yellow upon cally odorless oil boiling at 94-95 C./1 mm. Hg which exposure to light. Upon storing in the dark or upon melt O congealed upon cooling and melted at 28 C., and which ing, the color disappears. Upon dissolving the yellow is 1,1,4,4-tetramethyl 6-isopropyl 1,2,3,4-tetrahydronaph crystals in any colorless solvent, the yellow color dis thalene. appears and the solution remains colorless after long ex A mixture of 477 grams of 1,1,4,4-tetramethyl 6-iso posure to sunlight. Thus the product may be said to be propyl. 1,2,3,4-tetrahydronaphthalene, 41 grams of para 5 formaldehyde and 290 grams of 31% hydrochloric acid light-stable insofar as concerns its use as an ingredient of was agitated vigorously and warmed to 85 C. Then 580 a perfume composition. grams of 93% sulfuric acid was added during 7 hours, EXAMPLE 2 maintaining vigorous agitation and gradually increasing Preparation of 7-formyl 1,1,4,4-tetramethyl 6-ethyl the temperature to 90° C. Agitation was continued 17 1,2,3,4-tetrahydronaphthalene 20 hours further at 90° C. After cooling and settling, the A mixture of 93 grams of ethylbenzene and 2 grams of lower acid layer was discarded and the upper oil layer anhydrous ferric chloride was cooled to -5° C. and to it was dried over anhydrous soda ash, filtered and distilled was added a solution of 61 grams of 2,5-dichloro 2,5-di in vacuo in the presence of 4 grams of anhydrous Soda ash. methylhexane in 83 grams of ethylbenzene during 30 There was collected, in addition to 384 grams of recov minutes, maintaining the temperature at -5° C. and agi 25 ered 1,1,4,4-tetramethyl 6-isopropyl 1,2,3,4-tetrahydro tating continuously. After the evolution of hydrogen naphthalene, 76 grams of 7-chloromethyl 1, 1,4,4-tetra chloride had ceased the solution was quenched in Water, methyl 6-isopropyl 1,2,3,4-tetrahydronaphthalene as a washed to neutrality and distilled to yield, in addition to colorless oil boiling at 135 C./3.5 mm. Hg which rapidly the excess of ethylbenzene, 69 grams of a colorless oil solidified and had a melting point of 65-67 C. boiling at 90° C./1.5 mm. Hg and having Sp. Gr. (25 C.) 30 A mixture of 109 grams of 7-chloromethyl 1, 1,4,4- 0.920, n20 1.5165, which is 1,1,4,4-tetramethyl 6-ethyl tetramethyl 6-isopropyl 1,2,3,4-tetrahydronaphthalene, 55 1,2,3,4-tetrahydronaphthalene. grams of hexamethylenetetramine and 33 grams of water A mixture of 800 grams of 1,1,4,4-tetramethyl 6-ethyl was refluxed with vigorous agitation for 5 hours at a 1,2,3,4-tetrahydronaphthalene, 71 grams of paraformalde temperature of 118-132 C. The viscous mixture was hyde and 495 grams of 31% hydrochloric acid was agi 35 then steam distilled as in Example 1, carrying the inside tated vigorously and warmed to 64° C. Then 995 grams temperature finally to 170° C. The oily portion of the of 93% sulfuric acid was added during 8 hours, maintain distillate was washed as in Example 1 and distilled in ing vigorous agitation and gradually increasing the tem vacuo to produce 41 grams of 7-formyl 1, 1,4,4-tetra perature to 67° C. Agitation was continued 16 hours methyl 6-isopropyl 1,2,3,4-tetrahydronaphthalene as a further while the temperature was gradually increased to 40 colorless oil having a musk-like odor somewhat weaker 72° C. After cooling and settling, the lower acid layer than those of the products prepared in Examples 1 and 2, was discarded and the upper oily layer was dried over and boiling at 135 C./2 mm. Hg. The oil congealed anhydrous soda ash, filtered and distilled in vacuo in the upon standing and after crystallization from alcohol presence of 5 grams of anhydrous soda ash. There was yielded 36 grams of colorless crystals melting at 61.5-63 collected, in addition to 433 grams of recovered 1,1,4,4- 45 C. The crystals did not become yellow upon exposure to tetramethyl 6-ethyl 1,2,3,4-tetrahydronaphthalene, 379 light, as did those of Examples 1 and 2. The semicarba grams of 7-chloromethyl 1, 1,4,4-tetramethyl 6-ethyl Zone melted at 179-180 C. 1,2,3,4-tetrahydronaphthalene as a colorless oil boiling It will be readily apparent that our novel musk-like at 130° C./2 mm. Hg which rapidly solidified. After compounds can be employed in widely-varying formula crystallization from half its weight of naphtha, 340 grams 50 tions, depending upon the type of formulation, the odor was obtained in the form of colorless, odorless crystals effect desired, the desires of the compounder of the for melting at 64.5-66 C. mulation, etc. Conesquently, we do not wish to confine A mixture of 396 grams of 7-chloromethyl 1,1,4,4- ourselves to any particular formulation, but wish it to be tetramethyl 6-ethyl 1,2,3,4-tetrahydronaphthalene, 210 understood that our products can be employed as musks grams of hexamethylenetetramine and 129 grams of water 55 in perfume-containing formulations in general. By the was refluxed with vigorous agitation for 4/2 hours at a term "perfume-containing' we include, inter alia, per temperature of 116-124° C. The viscous mixture was fumes, cosmetics, soaps. then steam-distilled as in Example 1, carrying the inside Each of the musk materials made in accordance with temperature finally to 170° C. The oily portion of the this invention exhibits a desirable musk odor of high distillate was washed as in Example 1 and distilled in 60 order of persistence and not only has a marked ability to vacuo to produce 170 grams of 7-formyl 1,1,4,4-tetra "fix" the odor of perfume compositions containing it, but methyl 6-ethyl 1,2,3,4-tetrahydronaphthalene as a color also exhibits a subtle power to enhance the odor of such less oil having a strong, musk-like odor, boiling at compositions, even when used in very small amounts. 139 C./3 mm. Hg, congealing at 28 C. and melting at In this connection, each of the foregoing compounds 31 C. The semicarbazone melted at 1935-195 C. In 65 made in accordance with Examples 1 to 3, inclusive, the solid form the material turned yellow upon exposure exhibited a desirable and persistent musk odor when in to light, but in the liquid form, or in solution it remained corporated in ethyl alcohol to make a 5% by weight colorless. Thus, as in the case of the lower homologue solution. Soap cakes made by incorporating 0.1 percent described in Example 1, it may be said to be light-stable by weight of each of the compounds of Examples 1 to 3, insofar as concerns its use as an ingredient of a perfume 70 inclusive, to - white milled soap retained their sweet, composition. musk-like odors after exposure to light and air for 2 days, EXAMPLE 3 without discoloration. Rose and Muguet compositions Preparation of 7-formyl 1, 1,4,4-tetramethyl 6-isopropyl containing a small quantity (1% of a 5% alcohol solution 1,2,3,4-tetrahydronaphthalene by weight of total composition) of the compounds of A mixture of 200 grams of cumene and 10 grams of 75 Examples 1 to 3, inclusive, were made and found to 2,800,511. 5 6 possess increased floweriness, realism and smoothness, in the presence of a condensing agent, reacting the result as well as materially enhanced odor persistence. ing condensation product with formaldehyde and hydro The term “formaldehyde' in the claims includes prod chloric acid to yield the corresponding chloromethyl de lucts, such as paraformaldehyde, which yield formalde rivative, and finally converting the chloromethyl group of hyde during the reaction. the resulting compound into a CHO group by treatment The foregoing illustrates the practice of this invention of the chloromethyl derivative with hexamethylene tetra which, however, is to be construed as broadly as per C. missible in view of the prior art and limited solely by the 8. The process for preparing 7-formyl-1,1,4,4-tetra appended claims. methyl-6-ethyl-1,2,3,4-tetrahydronaphthalene, which com We claim: 0 prises condensing 2,5-dichloro-2,5-dimethyl hexane with 1. 6 - lower - alkyl - substituted, 7 - formyl - 1, 1,4,4- ethyl benzene in the presence of a condensing agent, re tetramethyl-1,2,3,4-tetrahydronaphthalenes. acting the resulting condensation product with formalde 2. 7 - formyl - 1,1446 - pentamethyl - 1,2,3,4 - hyde and hydrochloric acid to yield the corresponding tetrahydronaphthalenes. chloromethyl derivative, and finally converting the chloro 3. 7 - formyl- 1,1,4,4-tetramethyl - 6 - ethyl-1,2,3,4- 5 methyl group of the resulting compound into a CHO tetrahydronaphthalene. group by treatment of the chloromethyl derivative with 4. 7 - formyl - 1,144 - tetramethyl - 6 - isopropyl - hexamethylene tetramine. 1,2,3,4 - tetrahydronaphthalene. 9. The process for preparing 7-formyl-1,1,4,4-tetra 5. The process for preparing 6-lower-alkyl-substituted, methyl - 6 - isopropyl - 1,2,3,4 - tetrahydronaphthalene, 7 - formyl - 1,144 - tetramethyl - 1,2,3,4 - tetrahydro 20 which comprises condensing 2,5-dichloro-2,5-dimethyl naphthalenes, which comprises condensing 2,5-dihalo-2,5- hexane with cumene in the presence of a condensing dimethyl hexane with a lower-alkyl-substituted benzene agent, reacting the resulting condensation product with in the presence of a condensing agent, halomethylating formaldehyde and hydrochloric acid to yield the corre the resulting condensation product, and finally converting sponding chloromethyl derivative, and finally converting the halomethyl group of the resulting compound into a 25 the chloromethyl group of the resulting compound into CHO group. a CHO group by treatment of the chloromethyl derivative 6. The process for preparing 6 - lower - alkyl - sub with hexamethylene tetramine. stituted, 7-formyl-1,1,4,4-tetramethyl-1,2,3,4-tetrahydro naphthalenes, which comprises condensing 2,5-dichloro References Cited in the file of this patent 2,5-dimethyl hexane with a lower-alkyl-substituted ben 30 zene in the presence of a condensing agent, reacting the UNITED STATES PATENTS resulting condensation product with formaldehyde and 2,628,256 Campbell et al. ------Feb. 10, 1953 hydrochloric acid to yield the corresponding chloromethyl derivative, and finally converting the chloromethyl group FOREIGN PATENTS of the resulting compound into a CHO group by treat 35 452,537 France ------Mar. 8, 1913 ment of the chloromethyl derivative with hexamethylene tetramine. OTHER REFERENCES 7. The process for preparing 7-formyl-1,1,4,4,6-pen Brunson et al.; Jour. Am. Chem. Soc., vol. 62, pp. tamethyl-1,2,3,4-tetrahydronaphthalene, which comprises 37-44 (1940). condensing 2,5-dichloro-2,5-dimethylhexane with toluene 40 Hoffman-La Roche, 42 Chem. Abst, 7339 (1948).