US3658925A

US3658925A - Metalation of limonene and syntheses of limonene derivatives

Info

Publication number: US3658925A
Application number: US888893A
Authority: US
Inventors: William F Erman; Charles D Broaddus
Original assignee: Procter and Gamble Co
Current assignee: Procter and Gamble Co
Priority date: 1969-12-29
Filing date: 1969-12-29
Publication date: 1972-04-25
Anticipated expiration: 1989-04-25
Also published as: CH557383A; NL7018856A; GB1297569A; FR2072098A1; DE2064269A1; FR2072098B1

Abstract

DISCLOSED IS A NOVEL COMPOUND, 2-(4-METHYLCYCLOHEX-3EN-1-YL) ALLYLLITHIUM AND A PROCESS FOR ITS PRODUCTION. ALSO DISCLOSED ARE PROCESSES OF CONVERTING THIS NOVEL COMPOUND TO KNOWN AND USEFUL LIMONENE DERIATIVES. THESE DERIVATIVES FIND USE MAINLY AS PERFUME MATERIALS.

Description

United States Patent US. Cl. 260-665 R 3 Claims ABSTRACT OF THE DISCLOSURE Disclosed is a novel compound, 2-(4-methylcyclohex-3- en-lyl)allyllithium and a process for its production. Also disclosed are processes of converting this novel compound to known and useful limonene derivatives. These derivatives find use mainly as perfume materials.

BACKGROUND OF THE INVENTION This invention relates to a novel compound, 2-(4-methylcyclohex-3-en-1-yl)allyllithium, and a process for its preparation. As used hereinafter, the novel compound, 2- (4-methylcyclohex-3-en-l-yl)allyllithium will be referred to as metalated limonene. In addition, the invention concerns processes of conversion of the metalated limonene to fl-bisabolene, p-mentha 1,8() diene-9-ol, lanceol, lanceal, 9 carboXy-p-mentha-1,8(10)-diene and 9-carbomethoxy-p-mentha1,8( 10)-diene.

One of the more important classes of perfume materials has come from the class of materials known as the essential oils. These naturally occurring oils are extracts or distillates of the flowers, fruits, leaves, or roots of many different plants. Each essential oil, though, has an order or flavor that is characteristic of the plant from which it is isolated. The oils usually contain a large number of individual components, the relative proportions and nature of which differ depending on the plant source. Rather exhaustive studies in recent years have been conducted to determine the constituents found in the essential oils and, as might be expected, the studies have shown that not all of the constituents of a particular oil contribute to its aroma. Thus any attempt to duplicate the aroma of a naturally occurring essential oil does not necessarily require a synthesis of each individual constituent.

Many essential oils contain substances which have been termed the bisabolene sesquiterpenes. This class of material has been found in many important perfume essential oils such as lavender, lavandin, petitgrain, sandalwood, and various spice oils including ginger oil. These naturally occurring sesquiterpenes are known to possess a wide range of odor properties, many of which are described as being strong, woody, and/ or spicy.

In connection with the oil found in the wood of Santalum lanceolatum it was reported by Ruegg, Pfiffner, and Montavon in Recherches (:Paris), No. 15, 3 (1966) that one of the constituents, lanceol, possesses a woody odor and is consequently suitable as a perfume material. It was additionally disclosed in the same article that lanceal, the oxidation product of lanceol, possesses an odor reminiscent of sandalwood. However, the syntheses of these materials, as reported by Ruegg et al., supra and by Manjairez, Rios, and Gusman in Tetrahedron, 20, 333 1964) require many steps and are not commercially feasible. As will be described more fully later, it has now been discovered that these products can commercially be made by a relatively straight forward process through the conversion of a novel 3,658,925 Patented Apr. 25, 1972 "Ice intermediate, metalated limonene, to the desired limonene derivatives.

Other essential oils that have found wide use in the flavoring of food products, particularly baked goods, confectionery, and spicy table sauces are oil of ginger and various related spice oils. These maerials have also found use in the perfume industry where they impart an individual note to compositions of the oriental type. One of the components responsible for the aroma of these naturally occurring oils is the sesquiterpene fi bisabolene. This material has also been synthesized as reported by Ligouri and Ruzicka in Helv. Chim. Acta, 15, 3 (1932). However, this synthesis suffers from the drawback that it is awkward and commercially impractical. Such disadvantages, though, are eliminated by the novel synthesis described herein. By the present invention the desired product can be formed in a two-step process.

The invention disclosed herein also describes a novel process for the production of p-mentha-1,8(10)-dien-9-ol, a citrus oil constituent. The synthesis of this compound :as described hereinafter is simplified by conversion of the metalated limonene to the alcohol.

While the products lanceol, lanceal, and p-mentha-I, 8( 10)-dien-9-ol are useful in and of themselves as perfume materials, they are also useful in the reconstitution of natural essential oils. By reconstitution is meant the mixing together of all the various individual synthesized components in the same percentages as found in the naturally occurring oil.

Other perfume materials such as 9-carboxy-p-menthal.8(10)-diene and 9 carbomethoXy-p-mentha-1,8-(10)- diene can also be synthesized from the novel intermediate found in the instant invention, i.e., metalated limonene. The materials are known to possess a musty, earthy, minty, floral odor.

SUMMARY OF THE INVENTION Briefly stated, this invention concerns the discovery of metalation of a known and readily available compound, limonene, to form a stable intermediate and the further discovery that this intermediate can be converted to a wide variety of known and useful compounds.

Accordingly one of the objects of the present invention is to make an intermediate useful for the synthesis of known and useful perfume and flavor compounds More specifically, an object of the invention is to produce metalated limonene.

Another object of the invention is to provide a novel process for the conversion of limonene to metalated limonene Another object of the invention is to synthesize a variety of materials from metalated limonene.

More specifically, it is an object to convert metalated limonene to lanceol.

Another object is to convert metalated limonene to Ianceal.

Another object is to provide a novel process for the production of p-mentha-l,8(10)-dien-9-ol.

Another object of the invention'is to provide a process for the production of ,B-bisabolene from metalated limonene.

A further object is to produce 9-carboxy-p-menth'a-l, 8(10)-diene.

Still a further object is to provide a process for the production of 9-carboxy-p-mentha-L8(10)-diene from metalated limonene.

Another object is to produce 9-carbomethoxy-p-mentha-1,8( 10) -diene,

It is also an object to provide a process for the production of 9-carbomethoxy-p-mentha-1,8(10)-diene from metalated limonene.

Other objects of the present invention will become apparent from a reading of the following discussion and examples.

DISCUSSION AND PREFERRED EXAMPLES According to the present invention limonene is first metalated to form a stable intermediate suitable for the synthesis of many known and useful compounds. By metalation and used herein is meant a reaction involving metal-hydrogen exchange.

The starting material limonene is a readily available naturally occurring substance. It is one of the most widely distributed terpenes in nature and is found in several essential oils, in some as the main constituent, especially in citrus oils.

Limonene is found in optically active forms in both the levoand dextro-rotatory forms as well as the optically inactive or racemic-form known as dipentene. The optically inactive limonene or dipentene occurs in various wood turpentines. d-Limonene has been identified in oil of orange (about 90 percent), lemon, mandarin, lime, grapefruit, bergamot, neroli, petitgrain, elemi, caraway, dill, fennel, celery, orthodon oils, etc. l-Limonene occurs in several pine needle oils, the cone oil of Abies alaba, Russian turpentine oil, star anise, American wormseed, peppermint, spearmint, cajeput, Eucalyptus staigeriana, Congo copal resin, etc.

Separation of the limonene from essential oils is well known and need not be set out in detail here. Suflice it to say that two methods of obtaining limonene are (l) by fractional distillation; or (2) via certain crystalline adducts, e.g., the tetrabromides, which regenerate the hydrocarbons on debromination with zinc and acetic acid. d-Limonene, l-limonene, and dl-limonene are all commercially available, though, and the isolation or preparation of the starting material forms no part of this invention.

it should be recognized that both optically active forms of limonene, i.e. dand l-limonene and the optically inactive form, i.e. dl-limonene undergo the same chemical reactions and that the products obtained from each form differ only in optical activity. Thus, products obtained through this invention from the optically active forms are optically active while racemic limonene forms optically inactive products.

The optically active form of limonene used as the starting reactant would be dictated only by the absolute stereochemistry desired for the final product-It has been found that no loss of optical purity occurs during the conversion of either dor l-limonene to the stable intermediate, metalated limonene, and subsequent reactions to the final product desired. No racemization during the reactions has been detected. This is quite important where production of compounds with a specific configuration is desired. For instance, the naturally occurring ,B-bisabolene and lanceol are known to occur in nature only in the levo-form. Thus in any strict reconstitution of an essential oil containing either of these two materials it would be necessary to synthesize the levo-form. However, it should be recognized that the absolute configuration of a material is not always of importance and hence in such cases the stereochemical form of the limonene to be used is of little concern.

Metalation of limonene According to the present invention limonene is metalated by use of a strong metalating agent, for example, a complex of n-butyllithium and N,N,N',N'-tetramethylethylenediamine (TMEDA) which is suggested as a strong metalating agent in recent published articles by Langer in Trans. NY. Acad. Sci, Ser. V. 27, 741 (1965) and Eberhardt and Butte, J. Org. Chem. 29, 2928, (1964). The rnetalation of limonene is novel as well as the discovery that a stable product is formed therefrom that can be further reacted to form useful compounds. A schematic representation of the reaction is as follows:

CH Li CH2 Metalating C H; Agent CH2 I II Limonene 2(4-methylcyclohex-3-en-l-yl) allyllithiurn (metalated limonene) While the product formed upon metalation of limonene has been represented by the Formula II above, it should be noted that the product formed has not been isolated in pure form and characterized but that II has been theorized to be correct. Another possibility as to the formula of the metalation product would be on h Regardless of the correct formula of the reaction product, the resultant product of the metalation of limonene is referred to herein as 2-(4-methylcyclohex-3-en-l-yl)allyllithium or simply metalated limonene.

That metalation of limonene at the side chain position occurs is proved by derivatization of the reaction product to form known and/ or identifiable products. For instance, the mixture obtained by allowing excess limonene to react with the n-butyllithium-TMEDA complex was treated with carbon dioxide. After esterification with methanol, the product consisted predominantly of the fin -unsaturated ester represented by 111 in the following schematic equations:

This set of reactions shows that limonene undergoes metalation at the methyl group attached to the side-chain double bond to form an organolithium species represented by II. This intermediate reacts as an allylic carbam'on on derivatization with resultant substitution of a new group for a hydrogen atom found on the aforementioned methyl group.

The metalation of limonene is quite distinct in that metalation occurs at a position adjacent to only one of the olefinic bonds as noted from the above schematic equations, a result not predictable. This feature is quite important in that it allows the synthesis of very specific compounds without contamination from unrelated byproducts. Another important characteristic of the metalated limonene is that it is stable and can be stored at length prior to further reactions with various reagents.

As previously stated, the optical activity or configuration of the limonene depends only on the desired configuration of the product to be formed. If the absolute stereochemistry of the product is unimportant no care need be taken in the selection of the starting limonene.

The metalating agent referred to in the above mentioned articles by Langer and Eberhardt and Butte was found to be quite acceptable for the purpose of the present invention. However, this n-butyllithium-TMEDA complex is but one example of a strong metalating agent useful in the present metalation reaction.

In the present process of metalation many organolithium reagents can be used as the metalating agent. Preferably the organolithium is a primary alkyllithium having from 2 to carbon atoms. For example, ethyllithium n-propyllithium, or n-butyllithium are suitable. Most preferably n-butyllithium is used as the organolithium in the metalating agent.

It has been found that the metallation reaction of limonene does not occur in the presence of an organolithium alone but requires the addition of a complexing agent, preferably a ditertiary amine. Accordingly, ditertlary amine forms an important part of the metalating agent. Preferably the diamine contains 1 to 4 carbon atoms between the two amino groups. Examples of amines that are useful in the present invention are N,N,N',N-tetramethylethylenediamine (TMEDA), N,N,N,N' tetramethylmethylenediamine, N,N,N',N' tetramethylpropylenediamine, sparteine, and 1,4-diazabicyclo [2.2.2] octane (DABCO). TMEDA, DABCO, and sparteine are the preferred tertiary amines. The most preferred tertiary amine is T MEDA.

Theoretically one equivalent of an organolithium is required for each equivalent of limonene. A greater ratio of organolithium to limonene can be used, but slnce the organolithium is an expensive chemical a large excess is preferably avoided. However, excess limonene can be used with any non-reacted limonene being recovered by distillation prior to final purification of the product. The upper limit of the ratio of limonene to the organolrthium is only governed by the limitations imposed by having to separate the unreacted limonene from the final product. In practice it has been found that the range of rat1os based on mole equivalents of limonene to organolithium is preferably from one to ten equivalents of limonene for each one equivalent of organolithium. The most preferred ratio for the metalation process is two equivalents of limonene for each equivalent of organolithium.

The most preferred ratio of organolithium toamine has been found to be a 1:1 ratio based on mole equivalents.

However, mole ratios of 1:0.25-2 of organolithium to amine have been found to be satisfactory. Thus, the preferred ratios based on mole equivalents of organolithium: amine; limonene are 1:0.25-2:1-l0.

The metalation reaction of the present invention can be carried out by the following procedure. T o a container is charged a measured quantity of an organolithium in an inert solvent. While the solution is maintained under an atmosphere of dry inert gas, such as nitrogen or argon, the ditertiary amine is added. The solution should be stirred while the addition is made. Limonene is added dropwise to the resulting solution. The resulting mixture is allowed to stand under inert atmosphere for a length of time sufficient to insure a substantial completion of the reaction. Derivatization of the intermediate metalated limonene can now be effected by the direct reaction of the solution with the appropriate reagent, followed by standard work-up procedures. Excess limonene, if any, can be recovered by distillation prior to final purification of the product.

The metalated limonene of the present invention can be isolated by evaporating the solution containing metalated limonene to dryness in vacuo. Normally, it is inconvenient to do so since the metalated limonene is employed as an intermediate in the preparation of other compounds by subsequent reactions.

During the metalation reaction the reactants are preferably kept free from oxygen and moisture. For this reason a blanket of dry inert gas is maintained above the solution, such as nitrogen or argon as above mentioned. However, it should be realized these gases are but two examples of many gases that can be used. The primary criteria being that the gas preferably be free of moisture and inert.

It is not necessary to carry out the metalation in the presence of any solvent other than that in which the organolithium is dissolved. Any solvent that is used for the process should preferably be inert. The preferred solvents are the alkanes and cycloalkanes. Alkanes having having 5 to 10 carbon atoms have been found to be very suitable for the present invention. The most preferred alkane solvent is n-hexane. Cycloalkanes of from 5 to 10 carbon atoms also can be used as a solvent in the metalation reaction with cyclohexane being the most preferred solvent of the cycloalkanes. The amount of solvent used in the metalation reaction is not critical. The main consideration as to the concentration is the fact that as the dilution increases the reaction rate slows down. It has been found that when undiluted amine and limonene are added to the organolithium solution as described in the sequence above, an amount of solvent can be mixed with the organolithium prior to any limonene or amine additions to make an organolithium solution as dilute as 0.1 molar. A preferred concentration range based on the organolithium is 0.1 to 2 molar. The most preferred amount of solvent is an amount sufiicient to make a 1.5 molar solution of organolithium.

While room temperature is satisfactory for the purposes of the metalation reaction, slightly higher temperatures can be employed at atmospheric pressure as long as the boiling point of the solvent is not exceeded. The preferred temperature range at atmospheric pressure is 25 C. to 70 C. At higher temperatures some unwanted by-products begin to form. The metalation reaction is generally substantially finished after a time ranging from 1 to 24 hours depending on the temperature used. The most preferred time and temperature conditions for the reaction 32c (1:2;24 hours and room temperature (20 C. to

,H-Bisabolene Thesesquiterpene, S-bisabolene, can be prepared by derlvatlzation of metalated limonene. If it is desired to obtain the naturally occurring fl-bisabolene or to reconstitute an essential oil, consideration must be given to the optical configuration of the starting reactant used in producing metalated limonene. Once this determination is made the process can be carried out with the assurance that the final product will have the same absolute configuration as the limonene prior to any reactions. For instance, if it is desired to reconstitute an essential oil, the naturally occurring levo-form of S-bisabolene is preferred. Accordingly, the levo-form of limonene would be utilized 1n the metalation process. Further reaction of this 1- limonene would occur without any racemization with the resultant product free from any contamination by its enantiomers. Of course, frequently the absolute sterochemistry involved will be of no consequence, in which case the d-, l-, or dl-limonene can be used.

Regardless of the limonene used, however, subsequent chemical reactions will proceed in the same manner.

One of the advantages of forming fi-bisabolene according to the present process is that it can be produced by a one step process. That is, after limonene is metalated to the stable intermediate, metalated limonene, it does not have to be separated from the reaction mixture but rather, the desired reactant can simply be added with formation of the desired final product. Subsequent separation techniques are used to purify the final product.

In the present invention to form the fl-bisabolene, it is necessary to react the metalated limonene with a 1-halo-3- methyl-Z-butene according to the following:

where X=Br, C1, or I.

A process for the production of IV is carried out using metalated limonene as the starting reactant. Metalated limonene is produced in the manner discussed above. To a cooled solution containing the metalated limonene, l-halo- 3 methyl-2-butene is added dropwise. An atmosphere of inert gas is maintained during this addition. The rate of addition is adjusted so as to maintain the solution in a cooled state during the exothermic reaction. After the addition is complete the mixture is allowed to warm to room temperature and water is added dropwise. The organic phase is next diluted with ether and separated. The aqueous solution is extracted with ether. The combined organic solutions are washed successively with aqueous sodium chloride, e.-g., hydrochloric acid, e.g. 3 M, aqueous sodium bicarbonate, e.g. 5%, again with aqueous sodium chloride, and dried and evaporated. Excess limonene, if any, is separated from the resulting liquid by distillation. The colorless oil that remains comprises fl-bisa boleneand 4,4-dimethyl 2 (4-methylcyclohex-3-en-l-yl)-hexa-1,5- diene. These are separated and purified by preparative gas-liquid phase chromatography (GLPC) followed by mo lecular distillation, or 'by careful fractional distillation.

The reaction of the halide with metalated limonene is instantaneous and exothermic; thus, the reaction should be carried out at a reduced temperature. Temperatures as high as the boiling point of any inert solvent that is used can be employed but the preferred temperature range is 70 C. to 25 C. the most preferred temperature range is -70 C. to -20 C.

Oxygenation As a part of the present invention it has been discovered that the metalated limonene can also he used as an intermediate in the synthesis of a compound that is not only useful in itself, but also in the synthesis of other known and useful compounds. The oxygenation of metalated limonene followed by reduction of hydroperoxide intermediates is represented by the following schematic route:

1.1+ out on,

i 1,)02 2.)H O,Na2SO on. a OH:

on, g on,

tit

phere is maintained in the system during this reaction. When the reaction has ceased, a dropwise addition of water followed by an addition of sodium sulfite is made. The resulting two-phase mixture is next stirred vigorously, after which the layers are separated. The aqueous solution is then extracted with ether, and the combined organic solutions are washed successively with aqueous solutions of potassium iodide, sulfuric acid, and then water. The later two washings are back-extracted with ether, and the combined ether solutions are dried and evaporated. Any excess limonene can be recovered by distillation. Further distillation of the residue produces V.

In the above process itshould' be recognized that reducing agents other than sodium sulfit'e can be used. Such steps are well known in the art. a

The alcohol V has been found to have a camphoraceous, minty, soapy, piney aroma and thus finds use as perfume material. Also it can'be used in the synthesis of lanceol as reported by Ruegg et al., supra. Lanceol'itself occurs naturally in the levo-form and hence if it is desired'to obtain this specific optical configuration, l-lirnonene must be used as the starting reactant in the metalation process.

The acetate derivative of V has been reported as a constituent in many citrus oils and is also useful as an ingredient in soap perfumes. The acetate'derivativ'e is represented by the following:

E CH2 OO OCH;

The oxygenation of metalated limonene occurs instantaneously upon. addition of oxygen and is exothermic. Temperatures as high as the boiling point of the solvent, if any is used, can be employed. The preferred temperature range, however, is 70 C. to 25 C. The most preferred temperatures are 70 C. to +20? C carbonation In another aspect of the present invention metalated limonene can be used in' the synthesis of 9-carboxy-pmentha-1,8 10) -diene and 9-carbomethoxy-p-menta-l,8 (10)-diene. The reactions proceed as represented by the following schematic formulas:

I Q-carbomethQXy-pmentha-l, 8(10)-dien'e Both the acid VI and the ester III are useful as synthetic perfume ingredients possessing a fruity, musty,-earthy, floral, minty, fatty, sharp aroma.

A portion of a rnetalated solution prepared in the manner. above described is'added rapidly to a slurry of Dry Ice in ether, or in the alternative, carbon dioxide gas is passed through a cooled metalated limonene solution. When the resulting mixture warms. to room temperature, water is added, the layers separated, and the aqueous. layer is extracted with ether. The ether solution can be dried and evaporated to recover any excess limonene. The aqueous solution is acidified with dilute hydrochloric acid, extracted with ether and then the ether solution is dried and evaporated to give the acidification product, VI. A solution of this material in methanol containing sulfuric acid is heated to reflux, cooled, and poured into water. The resulting mixture is extracted with ether, and the resulting ether solution then washed with dilute aqueous sodium bicarbonate, water and dried and evaporated. Fractional distillation of the residue produces the ester III.

Compounds VI and III are both isolated by fractional distillation after their respective formations in the process as above described.

The carbonation reaction of metalated limonene is exothermic and occurs instantaneously. The temperature during the carbonation should remain below 25 C., though it is possible to use higher temperatures. The preferred temperature range when carbon dioxide gas is passed into a metalated limonene solution is 70 C. to '+25 C.

The above reactions involving the metalated limonene are preferably conducted in an atmosphere free from air or moisture to avoid unwanted by-products.

The following examples are introduced for the purpose of illustrating various processes found in the instant invention.

Example I (metalation of limonene).A flame-dried 500 ml. round-bottom flask, fitted with a magnetic stirring bar, pressure-equalized addition funnel, and gas inlet tube, was charged with 200 ml. (0.30 mole) of 1.5 M n-butyllithium in n-hexane. The contents of the flask were maintained under a static atmosphere of dry, inert gas (nitrogen) at all times. To the stirred solution was added dropwise 45 ml. (35 g., 0.30 mole) of dry TMEDA. A crystalline precipitate formed during the mildly exothermic reaction, which redissolved when the addition was complete. To the resulting yellow solution was added dropwise 100 ml. (84 g., 0.62 mole) of either dor l-limonene. Stirring was continued for 1 hour, andthe solution became dark red in color. The solution was allowed to stand overnight at room temperature (25 C.) prior to further use.

Metalated limonene is isolated by evaporating the solution to dryness in vacuo.

In the above reaction other organolithiums such as ethyllithium or n-propyllithium as well as other ditertiary amines such as tetramethymethylenediamine, tetramethylpropylenediamine, sparteine, or DA-BCO can be substituted on an equal mole basis for the n-butyllithium and/ or T MEDA, respectively, with equivalent results, i.e. metalated limonene is formed.

Example II (fi-bisabolene formation).A solution of metalated limonene was prepared in the manner described above from '67 ml. (0.10 mole) of 1.5 M n-butyllithium in n-hexane, ml. (-11.7 g., 0.10 mole) of TM-EDA, and 33 ml. (27.7 g.,- 0.20 mole) of l-limonene. The reaction flask was fitted with a low temperature thermometer and a pressure equalized addition funnel. The solution was stirred and cooled to 60 C. while static argon atmosphere in the system was maintained. 15.2 g. (0.10 mole) of 1-bromo-3-methyl-2-butene was added dropwise via the addition funnel. The rate of addition was adjusted so that the solution temperature did not exceed 40 C. The reaction mixture was allowed to warm to room temperature, and 50 ml. of water was added dropwise. The organic phase was diluted with ether and separated, and the aqueous solution was extracted with three 75-ml. portions of ether. The combined organic solutions were washed successively with 50 ml. of 5% aqueous sodium chloride, 75 ml. of 3 M hydrochloric acid (the acid-water solution wasv backwashed with ether), 50 ml. of 5% aqueous sodium bicarbonate, '50 ml. of 5% aqueous sodium chloride, and were dried and evaporated. Recovered limonene (13.8g.) was separated from the resulting liquid by distillation through a cm.

Vigreux column, B.P. 66-69 C. (17 mm.). Distillation of the residue through a short-path apparatus gave 3.0 g. of additional limonene and 8.64 g. (42% based on nbutyllithium, 53% based on limonene consumed) of a colorless oil, B.P. 60-80 C. (0.10 mm.). GLPC analysis showed that 94% of this material consisted of a 1:4 mixture of 4,4-dimethyl-2-(4-methylcyclohex-3-en-1-yl)- hexa-1,5-diene and 1/3-bisabolene. These were separated and purified by preparative GLPC followed by molecular distillation. The infrared spectrum of the l-fi-bisabolene so obtained was identical in all respects wtih published spectra of natural 1-,8-bisabolene.

Example III.-A procedure similar to Example II was carried out using d-limonene. d-fi-Bisabolene was obtained having spectral properties identical with those of the l-enantiomer.

In Examples II and III above 1-chloro-3-methyl-2- butene or 1-iodo-3-methyl-2-butene ,can be used in place of the 1-bromo-3-methyl-2-'butene with equivalent results.

Example IV.-(oxygenation of metalated limonene). A solution of metalated limonene was prepared in the manner of Example I from 50 ml. (0.075 mole) of 1.5 M n-butyllithium in hexane, 11.25 ml. (8.77 g., 0.075 mole) TMEDA, and 25.0 ml. (21.0 g., 0.154 mole) of dlimonene. The reaction flask was fitted with a low tem perature thermometer and a gas inlet tube extending beneath the surface of the liquid. The solution was stirred and cooled to 35 "C. while static argon pressure in the system was maintained. Air, which was first passed through a column of Drierite, was bubbled through the solution via the gas inlet tube, and the rate of addition of air was regulated so that the solution temperature did not exceed 20 C. When the exothermic reaction had ceased, the cooling bath was removed and the solution was allowed to warm to room temperature (the air addition was stopped when the temperature reached 0). After cautious, dropwise addition of 15 ml. of water, a solution of 18 g. of sodium sulfite in 70 ml. of water was added, and the resulting two-phase mixture was stirred vigorously for 17 hrs. The layers were separated, and the aqueous solution was extracted with three portions of ether. The combined organic solutions were washed successively with ml. of 5% sulfuric acid containing 5% potassium iodide, ml. of 5% sulfuric acid, and 100 ml. of water. The latter two washings were back-extracted with ether, and the combined ether solutions were dried and evaporated. Recovered limonene (10.8 g.) was separated from the resulting liquid by distil lation through a 20 cm. Vigreux column, B.P. =67-69'.5 (18 mm.). Distillation of the residue through a shortpath apparatus gave 3.74 g. (33%, based on n-butyllithium) of p-mentha-1,8(10)-diene-9-ol as a faintly yellow oil, B.P. 6671 C. (0.1 mm.), GLPC purity 97%. The analytical sample was obtained as a colorless oil after purification by preparative GLPC followed by molecular distillation. This alcohol possesses a camphoraceous, minty, soapy, piney odor.

'Example V (carbonation of metalated limonene). A solution of metalated limonene was prepared in the manner of Example I from 40 ml. (0.064 mole) of 1.6 M n-butyllithium in n-hexane, 9.6 ml. (7.5 g., 0.065 mole) TMEDA, and 21.2 ml. (17.8 g., 0.13 mole) of dlimonene. A 60-ml. portion of this solution was added rapidly by syringe to a slurry of Dry Ice in ether. When the resulting mixture had warmed to room temperature, water 'was added, the layers were separated, and the aqueous layer was extracted with two additional portions of ether. The combined ether solutions were dried and evaporated to give 10.2 g. of recovered limonene. The aqueous solution was acidified with dilute hydrochloric acid, extracted three times with ether, and the combined ether solutions were dried and evaporated to give 6.0 g. of the liquid acid VI. 9-carboxy-p-mentha-l, 8(l0)diene. A solution of this material in 100 ml. of methanol containing 1 ml. of concentrated sulfuric acid was heated to reflex for 2.5 hr., cooled, and poured into water. The resulting mixture was extracted with three portions of ether, and the combined ether solutions were washed successively with dilute aqueous sodium bicarbonate, Water, and'were dried and evaporated. Fractional distillation of the residue (5.3 g.) through a short Vigreux column gave a total of 1.98 g. (19% based on n-butyllithium, 25% based on limonene consumed) of 9-carbornethoxy-pmentha-1,8(10)-diene as a colorless oil in three fractions: fraction 1, 0.93 g., B.P. 6267 C. (0.2 mm.); fraction 2, 0.61 g., B.P. 6775 C. (0.2 mm fraction 3, 0.44 g., B.P. 75-9l C. (0.2 mm.). The purities of these fractions determined by GLPC were 92%, 90%, and 72%, respectively. The analytical sample was obtained from fraction 1 by preparative GLPC. This methyl ester was found to possess a fruity, musty, earthy, floral, minty, fatty, sharp aroma.

What is claimed is: 1. '2-(4methylcyclohex-3-en-l-yl)allyllithium.

2. A process of producing 2-(4-methylcyclohex-3-en-lyl)allyllithium comprising contacting limonene with a strong metalating agent consisting of a primary al-kyllithium having from 2 to 10 carbon atoms and a ditertiary amine having from 1 to 4 carbon atoms between the amino groups.

3. The process of claim 2 wherein the strong metalating agent comprises a n-butyllithium-N,N,N,N'-tetramethylethylenediamine complex.

References Cited UNITED STATES PATENTS 2,745,887 5/1956 Pines et a1. 2606'68 3,280,204 10/1966 Bloch 260- 665