States Patent Office 2,868,845 United faiented Jan. 3, 1959 1. 2 vacrol, a phenol known to possess valuable antioxidant properties, or reduced to carvomenthone. Carvenol can 2,868,845 be reduced to carvomenthol. I further find that esters of piperitol, as well as esters PREPARATION OF 2-MENTHENE-1-OL of 2-menthene-1-ol and 3-menthene-2-ol, will be pro Robert L. Webb, Jacksonville, Fla., assignor to The duced from the terpinene-hydrochloride if it is treated Gidden Company, Cleveland, Ohio, a corporation of under displacement conditions with sodium acetate or Ohio other salt of an organic acid rather than under solvolytic No Drawing. Application April 25, 1955 conditions. By solvolytic conditions I refer to the pres Serial No. 503,783 0. ence of a substantial aqueous phase whereby the chloride to carbon linkage is broken in the presence of water 5 Claims. (Ci. 260-631) molecules which tend to "solvolyze' the chloride ion and assist in its complete detachment from the organic por tion of the molecule. Under such hydrolysis conditions, It is the purpose of this invention to provide a method 5 little or no piperitol results from the treatment. How for treating alpha-terpinene-monohydrochloride to obtain ever, if the terpinene-monohydrochloride is treated with valuable terpene alcohols, esters and ethers, which are sodium acetate in the absence of water and suitably in useful intermediates for manufacture of thymol, carvacrol, the presence of a solvent such as acetic acid, then under piperitone, menthone, menthol and related compounds. these conditions menthenyl esters will be formed which Alpha-terpinene-monohydrochloride was prepared by 20 may be saponified to yield piperitol, as well as the two Wallach, Annalen, vol. 356, p. 198 (1907), by treating alcohols produced under Solvolytic conditions. the hydrocarbon with an equivalent weight of dry hy Further, either or both of the 2-menthene-1-ois can be drogen chloride. He found that the product he obtained converted to a mixture of the two piperitols by careful could be treated with a second molar equivalent of hy esterification with formic acid, suitably in the presence drogen chloride to form a dichloride of M. P. 52° C., but 25 of a buffer such as sodium acetate. There is formed by he did not otherwise investigate the monohydrochloride this esterification piperityl esters which can be readily as to reactions or structure. saponified to the mixed piperitols. Piperitols are readily Alpha-terpinene is readily produced by acid isomeriza hydrogenated to menthols, as is known. tion of turpentine, the pinenes, limonene and commer Further, when terpinene-monohydrochloride is reacted cially-available monocyclic hydrocarbon mixtures such 30 with sodium alcoholate or alcoholic alkali, a major por as originate as by-products in the synthesis of camphene, tion of the oxygenated material produced consists of terpineol and the like. From such acid isomerization ethers of carvenol and piperitol. Such ethers are valu mixtures, alpha-terpinene of high purity can be frac able because they are readily hydrolyzed by treatment tionated. with formic acid buffered with sodium acetate, and there It is therefore an object to convert alpha-terpinene to 35 by yield the formates of piperitol and carvenol, which in intermediates for synthesis of menthol and other flavor turn are readily saponified to the alcohols. and perfume chemicals. While I prefer to employ fairly pure alpha-terpinene It is a further object to convert alpha-terpinene to for preparation of the hydrochloride, in order to simplify piperitol. recovery of pure products, it is not necessay to employ It is a further object to convert alpha-terpinene to p 40 a highly purified material. Such impurities as cymene menthane derivatives oxygenated at the 1-, 2- and 3-po do not react with hydrogen chloride. Limonene would sitions of the p-menthane skeleton. yield limonene-monohydrochloride, which in turn would It is an additional object of this invention to provide yield alpha-terpineol on hydrolysis, and this could be a process for converting alpha-terpinene-monohydro readily separated from the 2-menthene-1-ol resulting from chloride to a mixture of 3-menthene-2-ol and 2-menthene 45 alpha-terpinene conversion because of its higher boiling 1-ol. - - point, but the terpineol would be more difficult to sep I have found that alpha-terpinene-monohydrochloride arate from the carvenol because the boiling points of these can be hydrolyzed in the presence of an aqueous alkaline lie close together. substance capable of neutralizing the hydrochloric acid Alpha-terpinene is converted to the monohydrochloride produced on hydrolysis, and thereby there is produced a in any convenient manner. The hydrocarbon can be mixture of alcohols consisting of 2-p-menthene-1-ol and 50 treated with dry hydrogen, chloride or aqueous hydrogen 3-p-menthene-2-ol, carvenol. chloride and in the presence or absence of solvent. The The 2-p-menthene-1-ol has been reported in the liter temperature employed is not critical. It will be found ature, Simonsen, The Terpenes, vol. , 2nd ed., p. 337, that any excess alpha-terpinene present above that re but the reported synthesis is of academic interest only quired to react with the available hydrogen chloride is because of the unavailability of commercial quantities readily recovered after the hydrolysis step. of the starting material and its high cost. This alcohol In carrying out the process of this invention, the alpha can be oxidized with Beckmann's chromic acid mixture terpinene-monohydrochloride is treated with a compound to piperitone. Piperitone is a valuable constituent of capable of replacing the chlorine atom with a hydroxyl various essential oils, and in addition, as is well known, group, an ester group or an ether group. Thus, the it can be hydrogenated to menthone and menthols which 60 chloride will be removed with formation of alcohols if are valued for their flavor and odor. - the reagent chosen is an alkali such as sodium or potas The 3-p-menthene-2-ol, carvenol, is also a known com sium hydroxide or an alkaline earth such as calcium hy pound, Simonsen, The Terpenes, vol. I, 2nd ed., p. 348, droxide. The corresponding carbonates and bicarbonates but the method of synthesis employed is of no commer can also be employed. While it is possible to operate . cial value. Carvenol is not known to occur in nature, 65 under Substantially anhydrous conditions, we prefer to . nor is the corresponding ketone, carvenone, which can employ aqueous systems whereby the alkaline hydrolysis be produced by Beckmann chromic acid oxidation of the agent, when used, is dissolved in water if it is soluble alcohol. Carvenone possesses an odor similar to car or Suspended in water if it is insoluble. Since calcium vone, an important constituent of oil of spearmint, car hydroxide and calcium carbonate are both cheap and away, etc., and is therefore useful as an odor and flavor 70 effective, they are preferred. Sodium acetate, formate chemical. Further, carvenone can be oxidized to car or other carboxylic acid salt can also be employed, and 2,868,845 3 4. if anhydrous conditions are employed, esters will result The hydrocarbon fraction was 50-60% ox-terpinene and from displacement of the chlorine. Such treatment is not 15-20% phellandrenes, as shown by comparison of its preferred, however, since the yields obtained of conversion infrared spectrum with spectra of the two pure hydro products are somewhat lower and no particular advantage carbons. Iesults. When using the alcoholates, anhydrous conditions The chloride fraction was stirred with H2O, Na2CO are necessary if ethers are desired, since in the presence and CaCO3 at the boiling point of the mixture to produce of water the alcoholates hydrolyze to the hydroxide and a hydrolysate containing the same alcohols as listed the alcohol. below. The temperatures employed in the hydrolysis step are The alcohol fractions were identified as 35% cis-2- not critical, but hydrolysis below 60° C. is slow; and it menthene-1-ol, 30% trans-2-menthene-1-ol and 35% 3 will be found that temperatures above about 140 C. menthene-2-ol, carvenol, by comparing them with spectra may result in undesirable decomposition. Temperatures of the known compounds. of 80 to 125 C. are satisfactory and convenient. While the published literature on 2-menthene-1-ol does After substantial or complete hydrolysis has taken not distinguish between the cis- and trans-forms, these place, the oil layer is separated from the aqueous layer i 5 isomers do exist, as shown in Example 2 of the copending and separated into its constituent parts, suitably by i3ain et al. application Serial No. 377,000, filed August 27, vacuum distillation. The lower boiling hydrocarbon 953. fractions consisting largely of phellandrene and alpha The residue contained a small amount of 3-menthene terpinene may be recycled to a succeeding hydrochlorina 2-cl and a trace of high boiling chlorides. The remainder tion step, so that the starting quantity of alpha-terpinene 20 was presumably polymeric material. can be finally converted to high yields of the mixed The more vigorous hydrolysis conditions employed alcohols. The presence of pheland rene as an impurity here resulted in isolation of less of the desired product in the recovered alpha-terpinene is not objectionable, since than was attained by operating under the milder condi it is convertible through its hydrochloride to 2-menthene-1- tions specified in Example 1. ol according to the copending application of Bain et al., Example 3 Serial No. 397,465, filed December 10, 1953, now Patent No. 2,827,499. 1000 grams of c-terpinene and 750 grams of 36% hy it is evident that alpha-terpinene-monohydrochloride is drochloric acid were stirred together at 20-30 C. for not a pure compound, as shown by the nature of its hy 24 hours. i. 127 grams of oil layer was recovered. Titra drolysis product. It is assumed that the terpinene and 30 tion of the recovered aqueous acid layer showed that it phellandrene recovered from the hydrolysis product result was 20-22% hydrochloric acid. from dehydrochlorination of the chloride product and 200 grams of the oil layer, 75 grams of CaCO3 and 300 possibly also to some extent from dehydration of the ml. of water were stirred for 18 hours at 95-105 C. The alcohols in working up the hydrolysis mixture. unreacted CaCO was then dissolved by adding sufficient Upon working up the hydrolysis mixture by fractiona 50% acetic acid, and the oil layer was separated to yield tion, some undecomposed terpinene-hydrochloride will 177 grams of hydrolyzed oil. The hydrolyzed oil was usually be found, and this may be recycled to a new batch fractionated through an efficient glass packed column. for hydrolysis. The next higher boiling fraction will be Infrared spectroanalysis of the fractions indicated that rich in 2-menthene-1-ol and finally 3-menthene-2-ol will the hydrolysate had the following composition: distill. Little high boiling residue or polymer will remain 40 65% hydrocarbons, B. P. 100 mm., 104-106 C. in the still. The alcohols may be further purified by re 3-5% organic monochlorides, B. P. 10 mm., 83-85 C. distiliation, crystallization, etc. 18-20% 2-p-menthene-1-ol, B. P. 10 mm., 88-90° C. The following examples are illustrative of the invention: 10-12% 3-p-menthene-2-ol, B. P. 10 mm., 101-103 C. Example I Example 4 100 grams, 0.662 mole, of 90% ox-terpinene was hydro chlorinated by bubbling HCl into the hydrocarbon at 200 grams of cy-terpinene-chloride, prepared as in Exam 25-30° C. When 24 grams of HCl, 0.662 mole, had ple 2, 100 grams of sodium acetate and 800 grams of been absorbed, the hydrochlorination was stopped. glacial acetic acid were mixed and heated for 6 hours The hydrochlorinated mixture, 200 ml. of H2O, 35 at 50-60° C. The oil was then recovered by diluting grams of NaCOs and 35 grams of CacO3 were stirred with water. The oil layer was saponified using a 20% at 100-105 C. for 18 hours. The oil layer was separated solution of KOH in methanol. The saponified oil was and analyzed by infrared analysis. This analysis showed fractionated through an efficient glass packed column. that the hydrolysate contained 70-75% alcohols and Infrared spectroanalysis of the fractions showed that the 20-25% hydrocarbons. The hydrocarbons were a mix 55 saponified oil was 60-65% hydrocarbons, 5-8% organic ture of the pheland renes and cy-terpinene. monochlorides, 6-8%. 2-p-menthene-1-ol, 8-10% 1-p- Example 2 menthene-3-ol, piperitols, and 8-10% 3-p-menthene-2-ol. 2808 grams of 80% ox-terpinene, 20.3 moles, was held Example 5 at 25-30 C, while HCl was bubbled into it. When the 200 grams of the organic chloride prepared as in hydrocarbon had absorbed 376 grams, 10.3 moles, the 60 Example 2, 50 grams NaOH and 500 ml. of methanol hydrochlorination was stopped. were mixed and allowed to stand 24 hours at 20-25 C. 3100 grams of the hydrochlorination product, 3000 ml. The oil was recovered by diluting with water. The oil HO and 763 grams of Ca(OH)2 were agitated at recovered was fractionated through an efficient glass 130-140° C. in an autoclave for 15 hours. The hydrolysis , packed column. infrared spectroanalysis of the fractions product was recovered by dissolving the excess lime by indicated that the hydrolysis product was 65-70% hydro d addition of HC and separating the oil layer. carbons, ox-terpinene containing some o-phellandrene, 2830grams of hydrolysate was recovered, indicating a weight loss of 8.8% during hydrolysis. The hydrolysate 3-5% organic monochlorides, 8-10% unsaturated ethers, was fractionated and the fractions were analyzed by in B. P. 10 mm., 83-85 C., and 10-12% alcohols, com 70 posed of 60-70% 2-p-menthene-1-ol and 30-40% of 3-p- frared analysis. This analysis indicated that they hy menthene-2-ol. drolysate had the following composition: Example 6 73% hydrocarbons 10 grams of 2-p-menthene-1-ol and a solution of 4 3-5% chlorides of c-terpinene grams of anhydrous sodium acetate in 25 grams of 90% 18-20% alcohols 75 4.7% residue formic acid were cooled separately to 0° C. and then 2,868,845 5 6 mixed. The mixture was agitated at 0-10 C. for 18 hours. Having described the invention, what is claimed is: The mixture was then saponified by refluxing it with a so 1. The process of preparing 2-menthene-1-ol which lution of excess 10% KOH in methanol. Infrared spectro comprises treating ox-terpinene with not more than one analysis of the saponification product showed that it was mole of HCl to form a monohydrohalide, and hydrolyzing a mixture of 90-95% piperitols and 5-10% 2-p-men the resulting chloride with water in the presence of a basic thene-1-ol. The piperitols were a mixture of about equal compound, said basic material being present in an amount quantities of cis- and trans-forms. Sufficient to neutralize HCl formed during the hydrolysis. It will be understood that the foregoing examples 2. The process of claim 1 in which the basic com are merely illustrative and that many variations can be pound is selected from the class consisting of alkali metal made therein without departing from the invention. IO and alkaline earth metal hydroxides, carbonates, car Thus, while only sodium compounds have been em boxylic acid salts and alcoholates. ployed as the alkali metal compounds in the examples, 3. The process of claim 1 in which the basic com other analogous alkali metal compounds such as the pound is calcium carbonate. potassium and lithium hydroxides and carbonates can be 4. The process for producing 2-menthene-1-ol which substituted therefor. Similarly, other alkaline earth metal comprises hydrolyzing ox-terpinene monohydrochloride bases such as barium and strontium hydroxides and car with water in the presence of a basic material, said base bonates can be used. being sufficient to neutralize hydrochloric acid formed Also salts of other alkali metals with other acids than during the hydrolysis. acetic can be employed, as can alcoholates of other 5. The process for preparing 2-p-menthene-1-ol which metals and other alcohols, the choice of which is pri 20 comprises treating c-terpinene with not more than one marily determined by economics and convenience. mole of HCl to form a monohydrohalide and hydrolyzing It will be appreciated, of course, that when water is the resulting monohydrohalide in the presence of a basic present, the alkali metal and alkaline earth metal oxides inorganic hydroxide in an amount sufficient to neutralize can be employed for the treatment of the C-terpinene the HCl formed during the hydrolysis. hydrochloride. This is because in the presence of water 25 the hydroxide is formed. In fact, any compound of the References Cited in the file of this patent general formula MX, wherein M is a positive radical, UNITED STATES PATENTS which when combined with the -OH radical forms a 1478,690 Andreau ------Dec. 25, 1923 relatively strong base, X is a monovalent negative radical, 2,609,388 Knapp et al. ------Sept. 2, 1952 which when combined with hydrogen forms a compound 30 of relatively weak acidity, a is a small whole number FOREIGN PATENTS equal to the valence of X, and b is a small whole num 532,614 Great Britain ------Jan. 28, 1941 ber equal to the valence of M, or which forms such a OTHER REFERENCES compound under the conditions employed, can be used Wallach: Annalen, vol. 356, pp. 198-9 (1907). for the treatment. It will also be appreciated that for Weygand: Organic Preparations, Interscience, N. Y., the highest yields of replacement products, it will be 1945; pp. 154-155. preferred not to use the strong bases, at least exclusively, . Wagner: "Manufacture of Terpineol-1,” Manufactur because of the dehydrochlorinating side reaction. ing Chemist XXII, March 1951, p. 99. When employing replacement conditions, other sol 40 Tishchenko et al.: J. Gen. Chem. (Russia), vol. 22, pp. vents of low dielectric constants can be employed, or, 798-802; (1952), Chem. Abs. 47, 5383e. if desired, the treatment can be carried out in the absence Royals: “Advanced Organic Chemistry,” Prentice-Hall, of solvent. The use of a solvent is preferred, however. Englewood Cliffs, N.J., 1954; pp. 264, 404, 405.