US3671558A - Novel esters and derivatives - Google Patents

Abstract

Novel aliphatic hydrocarbon esters, acids and alcohols having a backbone of at least 12 carbon atoms, a lower alkyl group at C-3, C-7 and C-11 and unsaturation or saturation at C-2,3, C-6,7 and/or C-10,11 which are substituents with, for example, halo, hydroxy, methylene, oxido, dihalo-methylene, and the like, and the esters and ethers of said hydroxy substituent useful as arthropod maturation inhibitors.

Description

United States Patent Siddall et al.

[ 51 June 20, 1972 [54] NOVEL ESTERS AND DERIVATIVES [72] Inventors: John B. Siddall, Palo Alto, Calif.; Jeans Pierre Calame, Locamo, Switzerland [73] Assignee: Zoecon Corporation, Palo Alto, Calif.

[22] Filed: July 22, 1969 [21] App1.N0.: 843,818

Related us. Application Data [52] US. Cl. ..260/410.9 R, 260/413, 260/468 P, 260/514 P, 260/294.3, 260/340.9, 260/345.7,

R, 260/473 C, 260/476 R, 260/482 R, 260/484 R,

260/486 R, 260/487, 260/488 H, 260/488 R,

260/493 R, 260/611 R, 260/612 D, 260/614 R,

[51] Int. Cl. ..C07c 69/74, C07c 61/16, AOln 9/24 [58] Field ofSearch ..260/410.9,4l3,408,405,468 P, 260/514 P [56] References Clted UNITED STATES PATENTS 3,413,351 11/1968 Eschenmoser et al ..260/586 Primary Examiner-Lewis Gotts Assistant ExaminerDiana G. Rivers AttorneyDonald W. Erickson [57] ABSTRACT Novel aliphatic hydrocarbon esters, acids and alcohols having a backbone of at least 12 carbon atoms, a lower alkyl group at C-3, C-7 and C-1 1 and unsaturation or saturation at C-2,3, C- 6,7 and/or C-10,11 which are substituents with, for example, halo, hydroxy, methylene, oxido, dihalo-methylene, and the like, and the esters and ethers of said hydroxy substituent useful as arthropod maturation inhibitors.

13 Claims, No Drawings NOVEL ESTERS AND DERIVATIVES This is a continuation-in-part of U.S. application Ser. No. 800,266, filed Feb. 18, 1969, which is a continuation-in-part of U.S. application Ser. No. 618,351, filed Feb. 24, 1967, which, in turn, is a continuation-in-part of the following U.S. applications: Ser. No. 579,490, filed Sept. 15, 1966; Ser. No. 590,195, filed Oct. 28, 1966; Ser. No. 592,324, filed Nov. 7, 1966; Ser. No. 594,664, filed Nov. 16, 1966; Ser. No. 605,566, filed Dec. 29, 1966; and Ser. No. 605,578, filed Dec. 29, 1966, each now abandoned.

This invention relates to novel aliphatic hydrocarbon ester derivatives and to processes for their preparation.

More particularly, the present invention relates to novel substituted aliphatic hydrocarbon esters, substituted aliphatic hydrocarbon acids and substituted aliphatic hydrocarbon alcohols (and the ethers and esters of said alcohols) having a backbone chain of 12 to 17 carbon atoms and a lower alkyl group at positions C-3, C-7 and C-1 1. These substituted aliphatic hydrocarbons can be prepared according to several methods described hereinafter. One method is to first prepare a substituted aliphatic hydrocarbon ester and then convert the substituted ester into the acid or alcohol to obtain novel substituted aliphatic hydrocarbon acids and alcohols (the alcohol, thereafter, can be converted into the ether or ester). Altematively, an unsubstituted aliphatic hydrocarbon ester is first converted into the corresponding acid or alcohol and thereafter the acid or alcohol is substituted according to the procedures described hereinafter.

' The terms aliphatic hydrocarbon ester, aliphatic hydrocarbon acid, and aliphatic hydrocarbon alcohol," as used herein, refers to compounds characterized by the following fonnula:

wherein each of R, R, R and R is a lower alkyl group and R represents the group -0R A a-on 1 wherein,

each of R- R R and R is lower alkyl; Z is hydrogen, hydroxy and ethers thereof, bromo, chloro or fluoro;

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-2,3 or one of the groups in which X is chloro or fluoto;

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro or fluoro;

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-6,7 or one of the groups 0, 0ir o012 or \()F1;

Z" is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro or fluoro;

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z', is a in which X is chloro or fluoro; and p R is the group COOR' or CH OR" in which R is hydrogen or lower alkyl and R is hydrogen, lower alkyl or cabboxylic acyl group; and the acid addition salts of the free acids, provided that when Z is hydrogen then Z is hydrogen.

Included within the present invention are the alkali metal and alkaline earth metal salts of the substituted aliphatic hydrocarbon acids. The salts of these acids include sodium, potassium, calcium, magnesium, barium, and the like.

As indicated above, the novel substituted aliphatic hydrocarbon esters, acids and alcohols (including the esters and ethers of said alcohols) can be derived from the compounds of formula XV. The compounds of formula XV can be prepared according to a process outlined as follows wherein R, R, R and R are as defined above, Alk is a lower alkyl group and D is phenyl.

In the practice of the above process (1- X), a dialkyl ketone (I) is reacted with an equal molar quantity, preferably an excess, of the Wittig reagent of Formula II in an organic solvent, e.g., dimethyl sulfoxide, at reflux temperatures to furnish the corresponding substituted Wittig reaction adduct of Formula Ill.

The Wittig reagent of Formula II can be prepared by conventional procedures, such as is described by Tripett, Advances in Organic Chemistry, Vol. 1, pp. 83-102, Trippett, Quarterly Review, Vol. 16-17, pp. 406-410; and Greenwald et al., Journal ofOrganic Chemistry 28, 1128 (1963) from the 4-ethylene ketal of a 1-halo-4-alkanone .by treatment with triphenylphosphinc followed by treatment with butyl or phenyl lithium.

The 4-ethylene ketal of the 1-halo-4-alkanone is obtained by subjecting the 4-keto compound to conventional ketalysis with ethylene glycol in benzene in the presence of an aryl sulfonic acid. The 1-halo-4-a1kanone, particularly the l-bromo derivative, can be prepared by known procedures such as that described in German Pat. No. 801,276 (Dec. 28, 1950), vide Chemical Abstracts 45, 2972h and by Jager et al., Arch. Pharm. 293, 896 (1960), vide Chemical Abstracts 55, 3470g. Briefly, these procedures involve treating butyrolactone with the desired alkyl alkanoate to provide the corresponding aacylbutyrolactone adduct. Treatment of the latter adduct with alkali metal halide, particularly sodium bromide, in aqueous sulfuric acid then provides the corresponding l-bromo-4-alkanone. Thus butyrolactone when treated with ethyl acetate gives a-acetylbutyrolactone which is, in turn, converted to lbromo-4-pentanone.

Hydrolysis of the Wittig reaction adduct (III) with aqueous acid affords the free ketone (IV).

By repeating the Wittig reaction just described on the thus formed ketone (IV) with the Wittig reagent (V) (prepared as described above), the corresponding diene adduct (V1) is obtained which is then hydrolyzed with aqueous acid to the dienone (VII).

The dienone of Formula Vll is then converted into the trienoate of Formula Vlll by treatment with a diethyl carboalkoxymethylphosphonate, such as diethyl carbomethoxymethylphosphonate '(VlII; Alk is methyl), in the presence of an alkali metal hydride, e.g., sodium hydride.

The aliphatic hydrocarbon ester (trienoate) of Formula VlIl can then be converted into the corresponding aliphatic hydrocarbon acid of Formula XX by treatment with an alkali metal salt, e,g., sodium carbonate, in aqueous alcohol, e.g., aqueous methanol or into the corresponding aliphatic hydrocarbon alcohol of Formula X by trgatment with, for example, lithium aluminum hydride.

Typical of the substituted aliphatic hydrocarbon esters, acids and alcohols which can be obtained from the above prepared starting materials are those of the following formulas:

(XVI) wherein R is hydrogen or lower alkyl; each of R, R, R and R is lower alkyl;

Z is hydrogen, hydroxy, chloro, fluoro or bromo;

Z is hydrogen, hydroxy, lower alkoxy, chloro, fluoro, or bromo, or when taken together with Z, a carbon-carbon double bond or one of the groups O, \CH2, \COIQ or CF 7' provided that when Z is hydroxy, chloro, fluoro or bromo, Z is other than hydrogen and when Z is hydrogen, Z is hydrogen;

Z is defined the same as Z; and Z is defined the same as Z and Z together with Z is defined the same as Z together with Z.

wherein, R, R, R and R are defined the same as above;

2" is hydrogen, hydroxy, chloro, fluoro or bromo; Z" is hydrogen, hydroxy, lower alkoxy, chloro, fluoro, or bromo, or when taken together with 2 a group, provided that when Z is hydroxy, chloro, fluoro or bromo, Z" is other than hydrogen and when Z" is hydrogen, 2 is hydrogen;

Z is defined the same as Z Z' is defined the same as Z" together with Z" is defined the same as Z" together with Z'; and R is the group COOR' or -CH,OR", wherein R is hydrogen or lower alkyl and R" is hydrogen lower alkyl or a carboxylic acyl group. I

wherein R, R R, R, Z, Z, Z and Z are as defined above in connection with Formula XVI; R" is hydrogen, lower alkyl,

or a carboxylic acyl group; and A is methylene, difluoromethylene, or dichloromethylene.

wherein, in the above formulas XlX through XXVlII,

each of R, R, R", R, R R and R is as defined above; R is hydrogen, lower alkyl or a carboxylic acyl group;

R is oxa, methylene, difluoromethylene, or dichloromethylene;

each of R and R is a lower alkyl of two to six carbon atoms;

and X is chloro, fluoro or bromo.

The term lower alkyl, as used herein, refers to straight or branched chain saturated aliphatic hydrocarbons having a chain length of one to six carbon atoms, e.g., methyl, ethyl, propyl, i-propyl, s-butyl, i-butyl, and the like. The term lower alkoxy, as used herein, refers to straight chain alkyloxy groups of one to six carbon atoms.

The carboxylic groups herein are derived from the corresponding carboxylic acids containing from 1 to 12 carbon atoms and possess straight, branched, cyclic or cyclicaliphatic chain structure which may be saturated, unsaturated, or aromatic and optionally substituted by groups, such as hydroxy, alkoxy containing up to five carbon atoms, acyloxy containing up to six carbon atoms, nitro, amino, halogeno, and the like. Typical esters thus include formate, acetate, propionate, enanthate, benzoate, trimethylacetate, t-butyl acetate, phenoxyacetate, cyclopentylpropionate, aminoacetate, B-chloropropionate, adamantoate, and the like, preferably a lower hydrocarbon carboxylic acyl group such as acetyl, propionyl, butyryl, and the like, containing up to about six carbon atoms.

The addition of a methylene group to an unsaturated position of the molecule can be performed selectively at C-2,3 by the reaction of. an unsaturated compound with dimethylsulfoxonium methylide base [prepared in the manner of Corey et al., Journal of the American Chemical Society 87, 1353 (1965)] in dimethylsulfoxide. Addition of the fused methylene group at the C-6,7 and C-l0,1l positions follows upon reaction of the unsaturated linkages with methylene iodide and a zinccopper couple in the manner of Simmons and Smith, .1. Am. Chem. Soc. 81, 4256 (1959). Preferably, the addition of the methylene group is conducted on an aliphatic hydrocarbon ester and thereafter the ester can be converted into the corresponding acid or alcohol by the procedures described hereinabove to obtain methylene substituted aliphatic hydrocarbon acids and methylene substituted aliphatic hydrocarbon alcohols. The thus obtained alcohol can then be etherified or esterified according to conventional etherification and esterification processes.

Similarly, the formation of the epoxide is selectively performed at the C-2,3position by reaction with hydrogen peroxide in aqueous alkali medium, such as is usually provided by sodium hydroxide. Addition of the oxido group at the 06,7 and C-l0,l1 positions is performed with m-chloroperbenzoic acid, preferably in methylene chloride or chloroform solution. The formation of an epoxide at C-2,3, C-6,7 and/or C-l0,l 1 in the case of acids and alcohols is preferably accomplished via the appropriate or desired epoxidation of an aliphatic hydrocarbon ester and then conversion of the ester into the acid or alcohol. If a methylene substituent and epoxide are to be introduced on the same backbone, it is preferable to perform the methylene addition first and then carry out epoxidation.

A difluoromethylene group at positions C-6,7 and C-10,l1 of an aliphatic hydrocarbon ester can be added by reacting the starting monoene, diene or triene with about 1.2 molar equivalents of trimethyltrifluoromethyl tin in the presence of sodium iodide in benzene/monoglyme solvent at reflux over a period of a few hours. By varying the mole ratio of the two reactants and the temperature and time of reaction, the reaction can be favored toward one or the other 6,7 and 10,11 mono adducts and the 6,7;l0,l1 bis adduct. The C-2,3 position is not attacked except under forcing conditions. Thereafter, the ester group can, if desired, be converted into the corresponding acid or alcohol by the procedures described above.

ln the case of adding difluoromethylene to an aliphatic hydrocarbon alcohol, introduction at any one of positions C- 2,3; 06,7; and C-l0,ll can be accomplished by using about 1.2 molar equivalents of trimethyltrifluoromethyl tin and sodium iodide in monoglyme and refluxing for about 2 hours. Similarly, the bis adducts at C-2,3;6,7, C-2,3;10,1l and C- 6,7;10,l1 can be prepared by following the above procedure with the exception of using about 2.5 molar equivalents of trimethyltrifluoromethyl tin and sodium iodide and refluxing for about 3 hours. Similarly, the tris adduct can be obtained by using about 5 to 10 molar equivalents of the reagents and refluxing for about 5 to 15 hours. The mono, his and tris adducts are separable by preparative gas-liquid chromatography.

A fused dichloromethylene group is introduced into an aliphatic hydrocarbon ester by reacting the C-6 or C-lO monoene; C-2,6, C-2,10 or C-6,10 diene; or C-2,6,l0 triene thereof with phenyldichlorobromomethyl mercury in benzene at reflux for from one to five hours. The relative yield of the C- 6,7 and C-l0,ll mono adducts and the C-6,7;10,11 bis adduct varies with the amount of mercury reagent and the reaction conditions employed. Generally, about or slightly more than one molar equivalent provides the mono adducts predominantly, the his adduct being favored by use of about 2.5 molar equivalents. The mono and his adducts are separable by gasliquid chromatography. These adducts can be converted into the correspondingly substituted aliphatic hydrocarbon acids and alcohol via the procedure described above. In the case of aliphatic hydrocarbon alcohol starting materials, dichloromethylene can be added at C-2,3 in addition to the formation of bis adducts (C-2,3;6,7, C-2,3;l0,l1, C- 6,7;l0,ll) by following the methods described above for aliphatic hydrocarbon esters and thereafter separating the adducts by gas-liquid chromatography. In addition, by using about four to six molar equivalents of the mercury reagent and refluxing for about 5 hours, the tris adduct can be obtained from corresponding 2,6,10- triene starting material.

A hydroxy, lower alkoxy, chloro, fluoro or bromo group at one or more positions on the backbone as indicated by formulas XVI through XXVllI can be introduced via a number of methods.

At the C-2,3-position, a monohydroxy substituent is introduced by treating a 2,3-oxido substituted aliphatic hydrocarbon ester with a mole or less of lithium aluminum hydride under mild conditions such as at temperatures of from 0 C to about 30 C for a few minutes, e.g., about 15-30 minutes to furnish the corresponding 1,3-diol and the corresponding 2,3-oxido-1-o1. For the preparation of 3-Ol-l derivatives of aliphatic hydrocarbon esters and acids, a ketone of formula Vll above is subjected to Reformatsky reaction (see for example, US. Pat. No. 3,031,481).

Etherification is thereafter conducted by methods known per se. For example, the hydroxy group can be treated with sodium hydride followed by an alkyl halide, such as ethyl bromide, to form the desired (lower)alkoxy group. 2- l-lalotetrahydropyran and 2-halotetrahydrofuran are utilized for the corresponding tetrahydropyran-Z-yl and tetrahydrofuran-Z-yl ethers. Acylation is likewise accomplished by known chemical processes, such as through the use of an acid anhydride in the presence of acid catalyst, for example, ptoluenesulfonic acid.

A 2,3-dihydroxy substitution can be accomplished by treating a 2,3-oxido substituted aliphatic hydrocarbon ester with 0.1 to 0.001 N perchloric acid in aqueous solution at room temperature for about 16 hours. A 2-hydroxy-3-lower alkoxy (straight chain) can be formed by similar perchloric acid treatment in a lower straight chain alcohol solvent medium. Alternatively, the 2,3-oxido starting material can be an aliphatic hydrocarbon acid or alcohol to furnish the corresponding C-2 and C-3 substituted compounds.

A 2-hydroxy-3-chloro, fluoro or bromo substitution can be similarly accomplished by treating a 2,3-oxido substituted aliphatic hydrocarbon ester/acid or alcohol with I-lCl, HF or I-lBr, respectively.

Each of the'C-6,7 and C-10,11 positions can be similarly substituted. Alternatively, monohydroxy substitution at C-7 and/or C-ll can be carried out by treating the unsaturated aliphatic hydrocarbon with aqueous formic acid as described more fully hereinafter. Thereafter, etherification or esterification can be carried out by the methods described above.

Monohalo (chloro, fluoro or bromo) substitution or introduction can be accomplished by treating an unsaturated aliphatic hydrocarbon ester or acid with hydrogen halide. Selective introduction at C-ll is obtained by treatment of the unsaturated compound with the appropriate hydrogen halide in carbon tetrachloride or other halogenated hydrocarbon solvents of low dielectric constant. Introduction at C-7 and C- 7,11 is favored by performing the reaction in diethyl ether or benzene. This halo introduction can be performed using as the starting material either a 6 or 10 monene, 2,10-diene, 2,6- diene, 6,10 -diene or 2,6,l-triene unsaturated aliphatic hydrocarbon ester, acid, or alcohol.

Dihalo (Cl, F or Br) introduction at C-10,ll or C-6,7 or

tetrahalo introduction at C-6,7,l0,l1 can be accomplished by treating an unsaturated aliphatic hydrocarbon ester, acid or alcohol with chlorine, fluorine or bromine in a chlorinated hydrocarbon solvent. A mixture of the dihalo and tetrahalo products is obtained which is separable by chromatography. The starting material can be either a monene, diene or triene. The 2-ene is unaffected by the reaction except in the case of aliphatic hydrocarbon alcohols in which case halo substitution at C-2 and 03 also takes place.

The bishydroxy derivatives (Z"=Z =hydroxy and/or Z=Z =hydroxy) are prepared from the precursor epoxide (introduced as described above) with aqueous acid as set forth above. Similarly, the procedure given above in the insertion of the 6(10)-hydroxy-7( 1 1 )-alkoxy and 6( 10)-hydroxy-7(l l halo substituents analagously apply.

In the preparation of the 6(10)-bromoand 6(10)-chloro- 7(1l)-hydroxy compounds, the starting unsaturated compound is treated with the appropriate quantity of N-bromoor N-chlorosuccinimide in aqueous organic solvent, such as dioxane. The 1 corresponding 7(l1)-alkoxy compounds are similarly prepared in the presence of dry alkanol solvent. Use of hydrogen fluoride starting with the corresponding oxido compounds affords some of the 6(10)-fluoro-7(1l)-hydroxy derivatives. Treatment thereof with acidified alkanol solution affords the corresponding (lower) alkoxy compounds.

In the practice of the above described elaborations on the compounds hereof, relative sensitivities of various groups to certain reaction conditions dictates the preference for a general pattern of reaction sequence. Thus, in accordance herewith, the methyleneation reaction is usually performed initially on the triene. As mentioned, this can be done selectively.

Theremaining sites of elaboration are generally epoxidized as the next step. This is particularly true for epoxidations at C- 2,3 position for which it is preferred not to have present a halo substituent on the backbone chain. However, since the acidic conditions required for the addition of hydrogen halides cleave the epoxide, it is preferred to insert the oxide after such reactions are performed unless, of course, the epoxide is required for the insertion of the hydroxy(alkoxy)-halo bis substituents, and the like.

With the exception of the above proviso for the oxido group, the fused halomethylene groups are preferably introduced after the fused methylene and oxido' groups are present since these reactions are compatible with these groups.

After all desired elaboration is complete, hydrogenation of any of the unsubstituted double bonds is, if desired, carried out. lilalogenation in the instance of introducing a tertiary halo atom is preferably conducted on the desired olefin isolated after hydrogenation.

Certain exceptions to the above general and preferred sequence exist; however, upon slight modification of the reactions according to the purposes desired in the preparation of particular compounds embraced by the present invention, chemical obstacles are overcome. These modifications are, as a whole, obvious to one skilled in the art and/or apparent by the preparative procedures set forth in the examples contained hereinafter.

Separation of the various geometric isomers can be performed at any appropriate or convenient point in the overall process. An advantageous and particular synthetically valuable point at which isomers can be separated by chromatography and the like is at the conclusion of each step of the backbone synthesis, that is, after preparing each of the compounds represented by formulas (VIII), (IX), and (X). Another advantageous point includes that just after the selective addition of the methylene group at C-2,3.

The novel substituted aliphatic hydrocarbon esters, acids and alcohols (including the esters and ethers of said alcohols) of the present invention are arthropod maturation inhibitors. They possess the ability to inhibit the maturation of members of the phylum Arthropoda, particularly, insects, in the passage from metamorphic stage to the next metamorphic stage. Thus, in the case of insects passing from the embryo stage to the larva stage, thence to the pupa stage, and thence to the adult stage, contact with an effective amount of a compound of the present invention, at any of the first three stages, inhibits passage to the next developmental stage with the insect either repeating passage through its present stage or dying. Moreover, these compounds exhibit ovidical properties with insects and are accordingly useful in combating them. These compounds are very potent and thus can be used at extremely low levels, for example, from 10 to 10- g. and are thus ad vantageously administered over large areas in quantities suitable for the estimated insect population. Generally the substances are liquids and for the purposes herein described, they can be utilized in conjunction with liquid or solid carriers. Typical insects against which these compounds are effective include mealworm, housefly, bollweevil, cornborer, mosquito, cockroach, moth, and the like.

Although not intending to be limited by any theoretical explanation, it appears that the effectiveness of these derivatives can be traced to their ability to mimic the activity of certain so-called juvenile hormone" substances, such as those described in US. Pat. Ser. No. 2,981,655 and Law et al. Proc. Nat. Acad. Sci. 55, 576 (1966). Because of the potency of the compounds of the present invention, they can be employed at extremely low concentrations, as noted above, to obtain reproducible and predetermined levels of activity. Juvenile hormone substances have been referred to as growth hormone also. Juvenile hormone was identified as methyl 10,11-oxido- 7-ethyl-3,l1-trimethyltrideca-2,6-dienoate using an extract of cecropia moths by Roeller et al., Angew. Chem. internat. Edit. 6, 179 (Feb., 1967) and Chemical & Engineering News, 48-49 (Apr. 10, 1967). A second juvenile hormone from the same source has been identified as methyl 10,1 l-oxido-3,7,1 1- trimethyltrideca-2,b-dienoate by Meyer et al., The Two .luvenile Hormones from the Cecropia Silk Moth, Zoology (Proc. N.A.S.) 60, 853 (1968). In addition to the natural juvenile hormones and the unidentified mixture of Law et al. above, some synthetic terpenoids have been reported to exhibit juvenile hormone activity Bowers et al., Life Sciences (Oxford) 4, 2323 (1965) methyl 10,11-oxido-3,7,11- trimethyldodeca-Z,o-dienoate; Williams et al., Journal of Insect Physiology 11, 569 (1965 BioScience 18, No. 8, 791 (Aug, 1968); Williams, Scientific American 217, No. l, 13 (July, 1967); Science 154, 248 (Oct. 14, 1966); Romanuk et al., Proc. Nat. Acad. Sci. 57, 349 (Feb, 1967) 7,11- dichloro of esters of farnesoic acid Canadian Pat. No.

795,805 (1968); Masner et al., Nature 219, 395 (July 27, 1968); US. Pat. No. 3,429,970 and 3,453,362 farnesene derivatives.

The compounds embraced by the terms "substituted Z is hydrogen, hydroxy and esters and ethers thereof,

aliphatic hydrocarbon ester,substituted aliphatic hydrocar- 5 bromo, h1 fluoro or h k n together with Z'", is u bon acid," substituted aliphatic hydrocarbon alcohol," formulas A, XVI through XXVllI and the examples are represented by the following formulas in which R, R', R, R", R, Z Z Z, Z and Z are as defined hereinabove.

in which,

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-l0,l1 or one of the groups and Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with 2, is a carbon-carbon double bond between C-6,7 or one of the groups in which,

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between 06,7 or one of the groups Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-2,3 or one of the groups carbon-carbon double bond between C-l0,ll or one of the groups OCh or CF2;

and V Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-6,7 or one of the groups bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-6,7 or one of the groups Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-2,3 or one of the groups diethylaminoacetate,

in which,

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-10,l 1;

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z", is a carbon-carbon double bond between C-6,7; and

Z is hydrogen, hydroxy and esters and ethers thereof, bromo, chloro, fluoro, or, when taken together with Z, is a carbon-carbon double bond between C-2,3, provided that at least one of Z, Z, Z, Z and Z is bromo, chloro or fluoro.

in which,

Z is hydrogen, hydroxy and esters and ethers thereof, or, when taken together with Z, is a carbon-carbon double bond between C-2,3;

Z is hydrogen, or hydroxy and esters and ethers thereof;

Z is hydrogen, hydroxy and esters and ethers thereof, or, when taken together with Z, is a carbon-carbon double bond between C-6,7;

Z is hydrogen or hydroxy and esters and ethers thereof; and

Z is hydrogen, hydroxy and esters and ethers thereof, or, when taken together with Z, is a carbon-carbon double bond, provided that at least one of Z Z, Z, Z and Z is hydroxy or the ester or ether thereof.

in which,

2*" is hydrogen; Z is hydrogen, or, when taken together with Z is a carbon-carbon double bond between 02,3; 2" is hydrogen; Z is hydrogen, or, when taken together with Z is a carbon-carbon double bond between C-6,7; 2 is hydrogen; and Z" is hydrogen, or, when taken together with Z'", is a carbon-carbon double bond between 010,1 1, provided that in formula XL at least one of R, R or R is lower alkyl of at least two carbon atoms.

The tenn "hydroxy and esters and ethers thereof, as used herein, refers to free hydroxyl and esters and ethers which are hydrolyzable to free hydroxyl. Typical esters are carboxylic esters of up to 12 carbon atoms which are saturated or unsaturated and of straight chain aliphatic, branched chain aliphatic, and cyclic or cyclic aliphatic structure, such as acetate, propionate, butyrate, valerate, caproate, enanthate, pelargonate, acrylate, undecanoate, phenoxyacetate, benzoate, phenylacetate, diethylacetate, trimethylacetate, trichloroacetate, t-butylacetate, trimethylhexanoate, methylneopentylacetate, cyclohexylacetate, cyclopentylpropionate, adamantoate, methoxyacetate, acetoxyacetate, aminoacetate,

B-chloropropionate, 2-chloro-4- nitrobenzoate, piperidinoacetate, and the like, preferably a lower hydrocarbon carboxylic ester containing up to six carbon atoms. Typical ethers are formed by etherification of the hydroxy group by tetrahydrofuran-Z-yl, tetrahydropyran-2-yl or by a monovalent hydrocarbon group of up to eight carbon atoms which can be of straight, branched, cyclic or cyclic aliphatic structure, such as alkyl, alkenyl, cycloalkyl, or am!- kyl, e.g., methyl, ethyl, propyl, butyl, pentyl, butenyl, phenethyl, benzyl, cyclopentyl, cyclohexyl, and the like.

The presence of at least one and optionally two double bonds in the foregoing compounds permits the existence of geometric isomerism in the configuration of these compounds. This isomerism occurs with regard to the double bond bridging the C-2,3 carbon atoms, the C-6,7 atoms, and C- 10,ll atoms. Obviously, isomerism at the C-l0,l I carbon atoms occurs only when R and R are different alkyl groups.

Thus, the isomers are the cis and trans of the monoene series and the cis,cis; cis,trans; trans,cis; and trans,trans of the diene series; each of which isomers in each series being in cluded within the scope of this invention. Preferably, the isomerism relative to the double bond between C-2 and C-3 is trans. Each of these isomers are separable from the reaction mixture by which they are prepared by virtue of their different physical properties via conventional techniques, such as chromatography, including thin-layer and gas-liquid chromatography, and fractional distillation.

The following examples will serve to further typify the nature of this invention. In some instances, the various isomeric forms are specified; however, in any of the reaction steps, the carbon-carbon double bonds can be cis or trans independent of the other or, isomeric mixtures can be employed.

EXAMPLE 1 Part A To a solution of 20.9 g. of the ethylene ketal of l-bromo-4- pentanone (obtained by treating l-bromo-4-pentanone with ethylene glycol in benzene in the presence of p-toluene-sulfonic acid) in ml. of benzene is added 20 g. of triphenylphosphine. This mixture is heated at reflux temperature for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo, and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until an orange solution is obtained and 3.8 g. of methyl ethyl ketone is then added. This mixture is stirred at about 25 C for about 8 hours, poured into water, and this mixture is extracted with ether. The ethereal extracts are concentrated and the residue thus obtained is added to a 0.1 N solution of hydrochloric acid in aqueous acetone and stirred for about 15 hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to yield a mixture of the cis and tans isomer of 6-methyl-5-octen-2-one which is separated by preparative gas-liquid chromatography into the individual isomers.

Part B To a solution of 20.9 g. of the ethylene ketal of l-bromo-4- pentanone in 100 ml. of benzene is added 20 g. of triphenylphosphine. This mixture is heated at reflux temperature for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo, and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until an orange solution is obtained and 5.5 g. of trans 6-methyl-5-octen-2-one (the ketone obtained in Part A) is then added. This mixture is stirred at about 25 C for about 8 hours, poured into water, and this mixture is extracted with ether. The ethereal extracts are concentrated and the residue thus obtained is added to a (H N solution of hydrochloric acid in aqueous acetone and stirred for about 15 hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to furnish a mixture of the trans, trans and cis, trans isomers of 6,10- dimethyldodeca-S,9-dien-2-one which is separated by preparative gas-liquid chromatography to the individual isomers.

By repeating the above procedure with the exception of using cis 6-methyl-5-octen-2-one in place of trans 6-methyl-5- octen-2-one, there is obtained a mixture of the cis, cis and trans, cis isomers of 6,10-dimethyldodeca-S,9-dien-2-one which is separated as described above.

Similarly, in the above procedure, instead of using either the trans or cis isomers of 6-methyl-5-octen-2-one as the starting material, there can be used a mixture of the isomers obtained in Part A in which case a mixture of the four isomers is obtained which can then be separated by preparative gas-liquid chromatography into the four isomers.

Part C A mixture of 11.2 g. of diethyl carbomethoxy methylphosphonate in 100 ml. of diglyme is treated with 2.4 g. of sodium hydride. This mixture is stirred until the evolution of gas ceases and 7.5 g. of trans, trans 6,10-dimethyldodeca- 5,9-dien-2-one is then slowly added with stirring, maintaining a temperature below 30 C. The mixture is stirred for about 15 minutes and then diluted with water and extracted with ether. These ethereal extracts are washed well with water, dried over sodium sulfate and evaporated to remove the solvent to furnish a mixture of the trans,trans,trans and cis,trans,trans isomers of methyl 3,7,11-trimethyltrideca-2,6,lO-trienoate which is separated by preparative gas-liquid chromatography.

The above procedure is repeated with the exception of using cis,trans 6,10-dimethyldodeca-5,9-dien-2-one as the starting material in place of the trans,trans isomer and there is obtained a mixture of the cis,cis,trans and trans,cis,trans isomers of methyl 3,7,1 1-trimethyltrideca-2,6,lO-trienoate.

Similarly, in the above procedure, in place of using either the trans,trans or cis,trans isomer of 6,10-dimethyldodeca- 5,9-dien-2-one as the starting material, there can be used as the starting material a mixture of isomers obtained in Part B and thereafter separating the individual isomers by preparative gas-liquid chromatography.

In the examples which follow, in some instances the isomeric forms are not specified; however, in each of the procedures set forth in the following examples, reference to the compound or compounds named is inclusive of each isomer or isomeric mixtures thereof. In other words, the following examples are illustrative of procedures which are applicable to compounds embracing individual isomers or isomeric mixtures of the type set forth hereinabove.

EXAMPLE 2 By repeating the process of Example 1 with the exceptions that in Part A thereof, methyl ethyl ketone is replaced with the ketones listed in column I and the ketone thus obtained is used in place of 6-methyl-5-octen-2-one in Part B, there is obtained the acid esters listed in column 11.

acetone methyl n-propyl ketone diethyl ketone methyl i-propyl ketone methyl n-butyl ketone ethyl n-propyl ketone methyl t-butyl ketone methyl i butyl ketone methyl s-butyl ketone ethyl i-propyl ketone methyl n-amyl ketone ethyl n-butyl ketone 3-ethy1-2- pentanone diisopropyl ketone methyl n-hexyl ketone S-ethyl-3- heptanone II methyl 3,7,l1-trimethyldodeca-2,6,10-trienoate methyl 3,7,1 l-trimethyltetradeca-2,6,10-trienoate methyl 3,7-dimethy1-1 l-ethyltrideca-2,6,10-trienoate methyl 3,7,11,12-tetramethyltrideca-2,6,10-trienoate methyl 3,7,1 l-trimethylpentadeca-2,6,l-trienoate methyl 3,7-dimethyl-l l-ethyltetradeca-2,6,10-trienoate methyl 3,7,11,12,12-pentamethyltrideca-2,6,l0- trienoate methyl 3,7,11,13-tetramethyltetradeca-2,6,10-trienoate methyl 3,7,11,12-tetramethyltetradeca-2,6,l0-trienoate methyl 3,7,12-trimethyl-1lethyltrideca-2,6,IO-trienoate methyl 3,7,11-trimethylhexa' deca-2,6,l0-trienoate methyl 3,7-dimethyl-l l-ethylpentadeca-2,6,lO-trienoate methyl 3,7,1l-trimethyl-l2- ethyltetradeca-2,6, 1 0- trienoate methyl 3,7,l2-trimethyl-l l- (i-propyl)-trideca-2,6,10- trienoate methyl 3,7,1 l-trimethylheptadeca'2,6,10-trienoate methyl 3,7-dimethyl-1 1,13-diethyltetradeca-2,6,l0- trienoate 4-deeanone methyl 3,7-dimethyl-1l-(npropyl)-heptadeca-2,6,l0- trienoate di-n-amyl methyl 3,7-dimethyl-l1-(nketone amyl)-hexadeca-2,6,10-

trienoate di-n-hexyl methyl 3,7-dimethyl-11-(nketone hexyl)-heptadeca-2,6,l0-

trienoate EXAMPLE 3 The process of Example 1 is repeated with the exception that in Part A thereof, l-bromo-4-pentanone is replaced with the l-bromo-4-ketones listed in Column III to furnish the acid esters listed in Column IV.

l-bromo-4- methyl 3,1l-dimethyl-7-ethy1- hexanone trideca-2,6,10-trienoate l-bromo-4- methyl 3,11-dimethyl-7-(nheptanone propyl)-trideca-2,6,l0-

trienoate l-bromo-4 methyl 3,11-dimethy17-(noctanone butyl)-trideca-2,6,10-

trienoate l-bromotmethyl 3,11-dimethyl-7-(nnonanone amyl)-trideca-2,6,l0-

trienoate methyl 3,11-dimethyl-7-(ipropyl)trideca 2,6,10- trienoate methyl 3,1l-dimethyl-7-(ibutyl)-trideca-2,6,10- trienoate methyl 3,1l-dimethyl-7-(tbutyl)-trideca-2,6,10- trienoate 1-bromo-5-methyl 4-hexanone l-bromo-6-methyl -heptanone l-bromo-5,5-dimethyl 4-hexanone methyl 3,1 l-dimethyl-7-(n-propyl)-tetradeca-2,6,l0- trienoate,

methyl 3 ,1 1-dimethyl-7-(n-butyl)-tetradeca-2,6,10- trienoate,

methyl 3 ,1 1-dimethyl-7-(n-amyl )-tetradeca-2,6 l 0- trienoate,

methyl 3 ,1l-dimethyl-7-(i-propyl)-tetradeca-2,6 ,10- trienoate,

methyl 3,1 1-dimethyl-7-(i-butyl)-tetradeca-2,6,l0- trienoate,

methyl 3 ,1 1-dimethyl-7-(t-butyl)-tetradeca-2,6, l0- trienoate,

methyl 3-methyl-7,l l-diethyltrideca-2,6,10-trienoate,

methyl 3-methyl-7-(n-propyl)-l1-ethyltrideca-2,6 ,10- trienoate,

methyl 3.-methyl-7-( n-butyl )-l l-ethyltrideca-2,6,10- trienoate,

methyl 3-methy1-7-(n-amy1)-1 l-ethy1trideca-2,6,l0- trienoate,

methyl 3-methyl-7-( i-propyl )-l 1-ethyltrideca-2,6 ,10- trienoate,

methyl 3-methyl-7-(i-butyl)-l 1-ethy1trideca-2,6,l0- trienoate,

methyl 3 -methyl-7-(t-butyl )-1 1-ethyltrideca-2,6 l 0- trienoate,

methyl 7-ethyl'3 ,1 1 ,l2-trimethyltrideca-2,6,10-trien0ate,

methyl 7-(n-propy1 )-3 ,1 1,1 2-trimethyltrideca-2,6,10- trienoate,

methyl 7-(n-butyl )-3,1 1,12-trimethyltricleca-2,6,10- trienoate,

methyl 7-(i-propyl)-3-3-ethyll1-methyltetradeca-2,6,l0- trienoate,

methyl 7-(i-butyl)-3-ethyl-1 lmethyltetradeca-2,6,ltrienoate,

methyl 7-(tbutyl)-3-ethyl-l l-methyltetradeca-2,6, l 0- trienoate,

methyl 3,7,1 1-triethyltrideca-2,6,10-trienoate,

methyl 7-(n-propyl)-3,1 l-diethyltrideca-2,6,IO-trienoate, methyl 7-(n-butyl)-3,1 1-diethyltrideca-2,6,IO-trienoate, meth yl 7-( n-amyl )-3,1 1-diethyltrideca-2,6 1 O-trienoate, methyl 7-(i-propyl)-3,l 1-diethyltrideca-2,6,lO-trienoate, methyl 7-( i-butyl )-3 ,1 1-diethyltrideca-2,6,10-trienoate, methyl 7-( t-butyl )-3,1 1-diethyltrideca-2,6, 1 O-trienoate, methyl 3 ,7 -diethyl-1 l-methylpentadeca-2,6,10-trienoate,

methyl 7-(n-propyl)-3 -ethyl-1 1-methylpentadeca-2,6, l 0- trienoate,

methyl 7-(n-butyl )-3 -ethyl-1 1-methylpentadeca-2,6, l 0- trienoate,

methyl 7-( n-amyl)-3 -ethyl-1 1 -methylpentadeca-2,6,10- trienoate,

methyl 7-(i-propyl)-3-ethyl-l 1 -methylpentadeca-2,6,10- trienoate,

methyl 7-(i-butyl)-3 -ethyl-l l-methylpentadeca-2,6,10- trienoate,

methyl 7-(t-butyl)-3-ethyl-1l-methylpentadeca-2,6,l0- trienoate,

methyl 3,7,11-triethyltetradeca-2,6,10-trienoate, methyl 7-(n-propyl)-3 ,1 1-diethyltetradeca-2,6,10- trienoate,

methyl 7-(n-butyl)-3,1 1-diethyltetradeca-2,6,l0-trienoate, methyl 7-(n-amyl )-3,1 l-diethyltetradeca2,6,10-trienoate, methyl 7-(i-propyl)-3,l 1-diethyltetradeca-2,6,IO-trienoate, methyl 7-( i-butyl )-3 ,1 1-diethyltetradeca-2,6,10-trienoate, methyl 7-(t-butyl)-3,1 1-diethyltetradeca-2,6,IO-trienoate,

methyl 3,7 -diethyl-l 1,12,12-trimethyltrideca-2,6,10- trienoate,

methyl 7-(n-propyl)-3-ethyl-l 1,12,12-trimethyltrideca- 2,6,l0-trienoate, and the like.

EXAMPLE 5 The procedure of Example 1 is repeated with the exception that in Part C, diethyl carbomethoxy methyl phosphonate is replaced with other dialkyl carboalkoxy methyl phosphonates, e.g. diethyl carbethoxy methyl phosphonate, diethyl n-propoxycarbonyl methyl phosphonate, dimethyl n-butoxycarbonyl methyl phosphonate, and the like, to furnish the corresponding alkyl 3,7,11-trimethyltrideca-2,6,lO-trienoate, e.g. ethyl 3,7,1 1-trimethyltrideca-2,6,IO-trienoate, n-propyl trimethyltrideca-2,6,lo-trienoate, n-butyl 3,7,11-trimethyltrideca- 1 ,6,l0-trienoate, and the like.

Similarly, by repeating the procedure of Examples 2, 3 and 4 with the exception that diethyl carbomethoxy methyl phosphonate is replaced with diethyl carbethoxy methyl phosphonate, diethyl n-propoxycarbonyl methyl phosphonate and dimethyl n-butoxycarbonyl methyl phosphonate, the corresponding ethyl 2,6,10-trienoates, n-propyl 2,6, l O-trienoates and n-butyl 2,6, l O-trienoates are obtained. For example,

ethyl 3,7,1 1-trimethyldodeca2,6,IO-trienoate,

n-propyl 3,7,1 1-trimethyldodeca-2,6,lO-trienoate,

n-butyl 3 ,7,1 1-trimethyldodeca-2,6, l O-trienoate,

ethyl 3 ,1 1-dimethyl-7-ethyltrideca-2,6, l O-trienoate,

n-propyl 3,1 1-dimethyl-7-ethyltrideca-2,6,IO-trienoate, nbutyl 3 ,1 1-dimethyl-7-ethy1trideca-2,6, 1 O-tn'enoate,

ethyl 3,1 l-dimethyl-7-ethyldodeca-2,6,10-trienoate,

n-propyl 3 ,11-dimethyl-7-ethyldodeca-2,6,lo trienoate,

n-butyl 3 ,1 l-dimethyl-7-ethyldodeca-2,6,10-trienoate,

ethyl 3-ethyl-7 ,1 1-dimethy1trideca-2,6, l O-trienoate,

n-propyl 3-ethyl-7,l 1-dimethyltrideca-2,6,lO-trienoate,

n-butyl 3-ethyl-7,l 1 -dimethyltrideca-2,6,10-trienoate,

ethyl 3-ethyl-7,1 l-dimethyldodeca-2,6,IO-trienoate,

n-propyl 3-ethy|-7,l 1-dimethyldodeca-2,6,l0-trienoate,

n-hutyl 3-ethyl7.l l-dimethyldodeca-2,6,IO-trienoate, ethyl .lfi-diothyhl l-methyltrideca-2,6,IO-trienoate,

22 n-propyl 3,7-diethyl-1 1-methyltrideca-2,6,10-trienoate, n-butyl 3,7-diethyl-11-methyltrideca-2,6,IO-trienoate, and the like.

EXAMPLE 6 A mixture of 1 g. of methyl 3,7,11-trimethyltrideca-2,6,l0- trienoate, 60 ml. of methanol, 0.1 g. of sodium carbonate, and 6 ml. of water is heated as reflux for 2 hours. The mixture is then cooled, diluted with water and extracted with ether. The ethereal extracts are washed with water, dried over sodium sulfate and evaporated to remove the solvent. The residue is subjected to fractional vacuum distillation to yield 3,7,11- trimethyltrideca-2,6, 1 O-trienoic acid.

By repeating the procedure of this example with the exception of substituting the other acid esters, preferably the methyl esters or ethyl esters obtained by the above procedures (Examples 2, 3, 4 and 5) for methyl 3,7,1 l-trimethyltrideca- 2,6,10-trienoate, there is obtained the corresponding free acids, e.g. 3,7,11-trimethyldodeca-2,6,IO-trienoic acid, 3,11- dimethy1-7-ethyltrideca-2,6,10-trienoic acid, 3,7-diethyl-1 lmethyltrideca-2,6,IO-trienoic acid, 3,1 l-dimethyl-7-ethyldodeca-2,6,10 -trienoic acid, 7,11-dimethyl-3-ethyltrideca- 2,6,10-trienoic acid, 7,1 1-dimethyl-3-ethyldodeca-2,6,10- trienoic acid, and the like.

EXAMPLE 7 A suspension of 0.5 g. of 5 percent palladium-on-carbon catalyst in 50 ml. of benzene is hydrogenated for 30 minutes. A solution of 2 g. of 6,10-dimethyldodeca-S,9-dien-2-one in ml. of benzene is added and hydrogenated with agitation until the theoretical amount of hydrogen has been absorbed. The catalyst is thereafter removed by filtration and the solution is evaporated to yield 6,10-dimethyldodec-S-en-2-one, 6,10-dimethyldodec-9-en-2-one and 6,10-dimethyldodecan-2- one which are separated and purified by preparative gas-liquid chromatography.

EXAMPLE 8 By repeating the procedure of Part A of Example 1 using, for example, the ketones listed in Column V in lieu of methyl ethyl ketone and using the ketone thus obtained for the procedure of Part B of Example 1, there are obtained the respective products listed in Column V1 which are hydrogenated using the procedure of Example 7 to afford 6,10-dimethylundec-5-en-2-one, 6,10-dimethylundec-9-en-2 one, and 6,10-dimethylundecan-Z-one; 6-methyl-10-ethyldodec-5-en-2-one, 6-methyl-10-ethyldodec-9-en-2-one, and 6-methyl-10-ethyldodecan-2-one; 6,10,1 1-trimethyldodec-5 en-2-one, 6,10,1 1-trimethyldodec-9-en-2-one, and 6,10,11- trimethyldodecan-Z-one; 6-methy1-10-ethyltridec-5-en-2-one, 6 methyl -l0-ethyltridec-9-en-2-one, and 6-methyl-10-ethyltridecan-2-one; and 6,10,11,1l-tetramethyl dodec-S-en-Z- one, 6,10,1 1,1 1-tetramethyldodec-9-en-2-one, and 6,10,1 1,1 l-tetramethyldodecan-Z-one, respectively.

acetone 6,10-dimethylundeca-S,9-dien- 2-one diethyl ketone 6-methyl-l0-ethyldodeca5,9-

dien-2-c ne methyl i-propyl 6,l0,l1-trimethyldodeca-S,9-

ketone dien-Z-one ethyl n-propyl G-methyll 0-ethyltrideca-5,9-

ketone dien-Z-one methyl t-butyl 6,l0,l 1,1 l-tetramethyldodeca ketone 5 ,9-dien-2-one By repeating the procedure of Part C of Example 1 using diethyl carbethoxymethyl phosphonate in place of diethyl carbomethoxymethyl phosphonate and using the mono-unsaturated and saturated 2-ketones prepared in this example in place of 6,10-dimethyldodeca-S,9-dien-2-one, the following ethyl esters are obtained:

ethyl 3,7,1 l-trimethyldodeca-2,6-dienoate,

ethyl 3,7,1l-trimethyldodeca-2,10-dienoate,

ethyl 3,7,1 l-trimethyldodec-Z-euoate,

.33, ethyl 3,7-dimethyl1 l-ethyltrideca2,6-dienoate, ethyl 3 ,7 -dimethyl-1 l-ethyltrideca-Z, l O-dienoate, ethyl 3 ,7 -dimethyl-l lethyltridec-2-enoate, ethyl 3,7,1 1,1Z-tetramethyltrideca-Z,6-dienoate, ethyl 3,7,1 1,l2-tetramethyltrideca-2,IO-dienoate, ethyl 3,7,1 1,1Z-tetramethyltridec-Z-enoate, ethyl 3 ,7 -dirnethyl-1 1-ethyltetradeca-2,6-dienoate ethyl 3 ,7-dimethyl-l l-ethyltetradeca-2, l O-dienoate, ethyl 3 ,7-dimethyl-l l-ethyltetradec-2-enoate, ethyl 3 ,7 ,1 1,12 ,1 Z-pentamethyltrideca-Z ,6-dienoate, ethyl 3,7 ,1 1,l2,12-pentamethyltrideca-2,10-dienoate, and ethyl 3 ,7 ,1 1,l2,1Z-pentamethyltridec-Z-enoate, respective- EXAMPLE 9 By repeating the procedure of Part A of Example 1 using the l-bromo-4-alkanones listed in Column VII in place of 1- bromo-4-pentanone, the corresponding ketones listed in Column Vlll are obtained which are used in Part B of Example 1 to afford the diunsaturated ketones listed in Column 1X. The

' diunsaturated ketones are hydrogenated using the procedure of Example 7 to yield 6-ethyl-l0-methyldodec-5-en-2-one, 6- ethyl-10-methyldodec-9-en-2-one, and 6-ethyl-10-rnethyldodecan-Z-one; 6-(n-propyl)-1O-methyldodec-S-en-2 one, 6- (n-propyl)-lO-methyldodec-Q-en-Z-one, and 6-(n-propy1)-l0- methyldodecan-Z-one; 6-(i-propyl)-10-methyldodec-5-en-2- one, 6-(i-propyl)-l0-methyldodec-9-en-2-one, and 6-(ipropyl)-l-methyldodecan-2-one; and 6-(t-butyl)-l0-methyldodec-S-en-Z-one, 6-(t-butyl)-10-methyldodec-Sl-en-2-one, and 6-(t-butyl)- l O-methyldodecan-Z-one, respectively.

Vll l-bromo-4-hexanone Vlll 7-methylnon-6-en- 3one l-bromo-4-heptanone 8-methyldec-7-en- 4-one l-bromo-5-methyl-4- 2,7-dimethylnon-6- hexanone en-3-one methyldodeca-S ,9-

dien-Z-one l-bromo-S ,S-di- 2,2,7-trimethylnon- 6-( t-butyl)-l0- methyl- 4-hexanone 6-en-3-one methyldodeca-5,9-

EXAMPLE By using the ketones listed in Column Vlll in place of 6- methyl-Smcten-Z-one and the ethylene ketal of the l-bromo- 4-alkanones listed in Column VII in place of the ethylene ketal of l-bromo-4-pentanone in Part B of Example 1, there is obtained 7-ethyl-l l-methyltrideca-6,l0-dien-3-one,

8-(n-propyl)- l 2-methyltetradeca-7,l l-dienA-one,

2,1 l-dimethyl-7-(i-propyl)trideca-6,l0-dien-3-one, and

2,2,1 l-trimethyl-7-(t-butyl)-trideca-6,10-dien-3-one, respectively, which are hydrogenated using the procedure of Example 7 to yield 7-ethyl-1 l-methyltridec--en-B-one,

7-ethyl-l 1 -methyltriclec-l 0-en-3 -one, and

7-ethyl-l 1 -methyltridecan-3-one;

8-(n-propyl)-12-methyltetradec-7-en-4-one,

8-(n-propyl l Z-methyltetradec-l l-en-4-one, and

8-(n-propyl)-l2-methyltetradecan-4-one;

2,1 1-dimethyl-7-(i-propyl)-tridec-6-en-3-one,

2,1 1-dimethyl-7-(i-propyl)-tridec-l0-en-3-one, and

2,1 l-dirnethyl-7-(i-propyl)-tridecan-3-one; and

2,2,1 1-trimethyl-7-(t-butyl)-tridec-6-en-3-one,

2,2,1 1-trimethyl-7-(t-butyl)-tridec-10-en-3-one, and

2,2,1 l-trimethyl-7-(t-butyl )-tridecan-3 -one, respectively.

The thus-obtained mono-unsaturated ketones and saturated ketones are subjected to the procedure of Part C of Example 1 using diethyl carbethoxymethyl phosphonate to obtain the following ethyl esters:

ethyl 3,7-diethyl-l 1-methyltrideca-2,6-dienoate,

ethyl 3 ,7-diethyl- 1 l-methyltrideca2, l O-dienoate,

ethyl 3 ,7 -diethyl-l l-methyltridec-Z-enoate,

ethyl 3,7-(n-propyl)-1 l-methyltrideca-2,-dienoate,

ethyl 3 ,7 -(n-propyl )-1 l-methyltrideca-2, 1 O-dienoate,

ethyl 3 ,7-(n-propyl )-1 l-rnethyltridec-Z-enoate,

ethyl 3,7-di(i-propyl)-1 l-methyltrideca-2,6-dienoate,

ethyl 3,7-di(i-propyl)-l l-methyltrideca-2, 1 O-dienoate,

ethyl 3 ,7-di(i-propyl)-1 l-methyltridec-2-enoate,

ethyl 3,7-di( t-butyl )-l l-methyltrideca-2,o-dienoate,

ethyl 3 ,7-di(t-butyl )-1 1-methyltrideca-2, l O-dienoate, and

ethyl 3,7-di(t-butyl)-l l-methyltridec-2enoate, respectively.

EXAMPLE 1 1 X1 6-ethyll q-methyluncleca-fifl dien-Z-one tS-(n-propyl )-10-methylundeca- 5 ,9-dien-2-one 6-(i-propyl)-l(Lmethylundeca- 5 ,9-dien-2-one 6-(t-butyl)-lO-methylundeca- 5,9-dien-2-one X 7-m ethyloct-fi-en-3 -one B-m ethylnon-7-en-4-one 2,7-dirnethyloct-6-en-3-one 2,2,7-trimethyloet-6-en'3-one The compounds listed in Column X1 are hydrogenated ac cording to the procedure of Example 7 to yield 6-ethyl-10- methylundec-S-en-Z-one, 6-ethyl-10-methylundec-Q-en-Z-one and 6-ethyl-IO-methylundecan-Z-one; 6-(n-propyl)- 10- methylundec-S-en-Z-one, 6-( n-propyl)-l0-methylundec-9-en- 2-one and 6-(n-propyl)-lO-methylundecanZ-Qne; 6-(ipropyl)-10-methylundec-S-en-2-one, 6-(i-propyl l 0- methylundec-9-en-2-one and 6-(i-propyl)-lO-methylundecan- 2-one; and 6-(t-butyl)-l0-methylundec-5-en-2one, 6-(t-butyl)-10-methlundec-9-en-2-one and 6-(t-butyl)-l0-methylundecan-Z-one, respectively.

The thus-obtained mono-unsaturated and saturated ketones are treated with diethyl carbethoxymethylphosphonate using the procedure of Example 1 (Part C) to afford:

ethyl 3,1 1-dirnethyl-7-ethyldodeca-2,6-dienoate,

ethyl 3,1 l-dimethyl-7-ethyldodeca-2,10-dienoate,

ethyl 3,1 l-dimethyl-7-ethyldodec-2-enoate,

ethyl 3,1 l-dimethyl-7-(n-propyl)-dodeca-2,o-dienoate,

ethyl 3 ,1 1 -dimethyl-7-(n-propyl )-dodeca-2, l O-dienoate,

ethyl 3,1 l-dimethyl-7-(n-propyl)-dodec-2-enoate,

ethyl 3,1 l-dimethyl-7-(i-propyl)-dodeca-2,6-dienoate,

ethyl 3,1 l-dimethyl-7-(i-propyl)-dodeca-2,lO-dienoate,

ethyl 3,1 l-dimethyl-7-(i-propyl)-dodec-2enoate,

ethyl 3,1 1-dimethyl-7-(t-butyl)-dodeca-2,6-dienoate, ethyl 3,1 1dimethyl-7-(t-butyl)-dodeca-2,IO-dienoate, and

ethyl 3,1 1-dimethyl-7-(t-butyl)-dodec-2-enoate, respectively.

EXAMPLE 12 The mono-unsaturated ketones listed in Column X are substituted in place of 6-methyl-5-octen-2-one and the ethylene ketal of the 1-bromo-4-hexanone is used in place of the ethylene ketal of 1-bromo-4-pentanone in the process of Example 1 (Part B) to give 7-ethyl-l1-methyldodeca-6,10-dien- 3-one, 7-(n-propyl)-11-methyldodeca-6,lO-dien-3-one, 7-(ipropyl)-l1-methyldodeca-6,10-dien-3-one and 7-(t-butyl)- 1l-methyldodeca-6,10-dien-3-one, respectively, which are hydrogenated using the procedure of Example 7 to yield 7- ethyl-l 1-methyldodec-6-en-3-one, 7-ethyl-11-methyldodecl-en-3one and 7-ethyl-1l-methyldodecan-3-one; 7-(npropyl)-l l-methyldodec-6-en-3-one, 7-(n-propyl)-1 l-rnethyldodec-l0-en-3-one and 7-(n-propyl)-1l-methyldodecan-3- one; 7-(i-propyl)-1lmethyldodec6-en-3-one, 7-(i-propyl)- 1l-methyldodec-10-en-3-one and 7-(i-propyl)-1l-methyldodecan-3-one; and 7-(t-butyl)-11-methyldodec-6-en-3-one, 7-(t-buty1)-l 1-methyldodec-10-en-3-one and 7-(t-butyl)-11- methyldodecan-3-one, respectively.

The thus-obtained mono-unsaturated and saturated 3- ketones are treated with diethyl carbethoxymethylphosphonate using the procedure of Example 1 (Part C) to give:

ethyl 3,7-diethyl-11-methyldodeca-2,6-dienoate,

ethyl 3,7-diethyl-l l-rnethyldodeca-2,10-dienoate,

ethyl 3,7-diethyl-1 l-methyldodec-Z-enoate,

ethyl 3-ethyl-7-(n-propyl)-1 l-rnethyldodeca-2,6-dienoate,

ethyl 3-ethyl-7-(n-propyl)-1 1-methyldodeca-2,10-dienoate,

ethyl 3-ethyl-7-(n-propyl)-l 1-methyldodec-2-enoate,

ethyl 3-ethyl-7-(i-propyl)-l 1-methy1dodeca-2,6-dienoate,

ethyl 3-ethyl-7-(i-propyl)-l 1-methyldodeca-2,10-dienoate,

ethyl 3-ethyl-7-(i-propyl)-1 1-methyldodec-2-enoate,

ethyl 3-ethyl-7-(t-butyl)-l1-rnethyldodeca-2,6-dienoate,

ethyl 3-ethyl-7-(t-butyl)-11-methyldodeca-2,IO-dienoate, and

ethyl 3-ethyl-7-(t-butyl)-1 l-methyldodec-Z-enoate, respectively.

By repeating the procedure of this example using the ethylene ketal of the other l-bromo-4-alkanones listed in Column VII in place of the ethylene ketal of l-bromo-4-hexanone, the corresponding 3-(n-propyl)-, 3-(i-propyl)-, and 3- (t-butyl)-ethyl esters of the 3-ethyl esters enumerated in the preceding paragraph are obtained, for example, ethyl 3-(npropyl)-7-ethyl-11-methyldodeca-Z,6-dienoate, ethyl 3-(npropyl)-7-ethyl-1l-methyldodeca-Z,IO-dienoate and ethyl 3- (n-propyl)-7-ethy1-l 1-methyldodec-2-enoate.

EXAMPLE 13 The procedure of Example 1 (Part A) is repeated using diethyl ketone in place of methyl ethyl ketone and l-bromothexanone in place of l-bromoi-pentanone to give 7-ethylnon-6-en-3-one. 13y repeating this procedure using ethyl ipropyl ketone, ethyl n-propyl lcetone, ethyl t-butyl ketone,

- ethyl n-butyl ketone, and di-i-propyl lcetone in place of diethyl hydrogenated using the procedure of Example 7 to yield 7,11- diethyltridec-6-en-3-one, 7,11-diethyltridec-10-en-3-one and 7,1 1-diethyltridecan-3-one; 1 1-(i-propyl)-7-ethyltridec-6-en- 3-one, ll-(i-propyl)-7-ethyltridec-l0-en-3-one and ll-(ipropyl)-7-ethyltridecan-3-one; 7,1l-diethyltetradec-6-en-3- one, 7,1l-diethyltetradec-10-en-3-one and 7,11-diethyltetradecan-S-one; 1l-(t-butyl)-7-ethyltridec-6-en-3-one, 11- (t-butyl)-7-ethyltridec-l0-en-3-one and 1l-(t-butyl)-7-ethyltridecan-3-one; 7,11-diethylpentadec-6-en-3-one, 7,11- diethylpentadec-l 0-en-3-one and 7,1 l-diethylpentadecan-3- one; and 7 -ethyl-11-(i-propyl)-12-methyltridec-6-en-3-one, 7-ethyl-1 1-(i-propyl)-12-methyltridec-10-en-3-one and 7- ethyl-l 1-(i-pr0pyl)-12-methyltridecan-3-one, respectively, each of which are treated with diethyl carbethoxymethylphosphonate using the procedure of Example 1 (Part C)to afford:

ethyl 3,7,1 1-triethyltrideca-2,6-dienoate,

ethyl 3,7,1 l-triethyltrideca-2,10-dienoate,

ethyl 3 ,7,1 1-triethyltridec-2-enoate,

ethyl 3,7,1 1-triethyl-lZ-methyltrideca-Z,6-dienoate,

ethyl 3,7,1 l-triethyl-l2-methyltrideca-2,10-dienoate,

ethyl 3,7 ,1 l-triethyll Z-methyltridec-Z-enoate,

ethyl 3,7,1 1-triethyltetradeca-2,6-dienoate,

ethyl 3 ,7,1 l-triethyltetradeca-2, l O-dienoate,

ethyl 3,7,1 l-triethyltetradec-2-enoate,

ethyl 3,7,1l-triethyl-l2,lZ-dimethyltrideca-Z,6-dienoate,

ethyl 3,7,11-triethyl-l2,12-dimethyltrideca-2,10-dienoate,

ethyl 3,7,1 1-triethyl-12, l 2-dimethyltridec-Z-enoate,

ethyl 3,7,1 1-triethylpentadeca-2,-dienoate,

ethyl 3 ,7,1 1-triethylpentadeca-2,10-dienoate,

ethyl 3,7,1 1-triethylpentadec-Z-enoate,

ethyl 3,7-diethyl-1 l-(i-propyl)- l 2-rnethyltrideca-2,6- dienoate,

ethyl 3,7-diethyl-1 1-( i-propyl)-l2-methyltrideca-2,10- dienoate, and

ethyl 3 ,7-diethyl-1 1-(i-propyl)-1Z-methyltridec-Z-enoate, respectively.

EXAMPLE 14 Each of 6,10-dimethyldodec-5-en-2-one, 6,10-dimethyldodec-9-en-2-one and 6,10-dimethyldodecan-Z-one is treated with diethyl carbethoxyrnethylphosphonatc using the procedure of Example 1 (Part C) to yield ethyl 3,7,11- trimethyltrideca-Z,6-dienoate, ethyl 3,7,1 l-trirnethyltrideca- 2,10-dienoate and ethyl 3,7,11-trimethyltridec-2-enoate, respectively.

EXAMPLE 15 A solution of 20.9 g. of the ethylene ketal of methyl 3- bromopropyl ketone (obtained by treating the ketone with ethylene glycol in benzene in the presence of p-toluenesulfonic acid) in ml. of benzene is treated with 20 g. of triphenylphosphine. This mixture is heated at reflux temperatures for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until a red solution is obtained and 7.2 g. of -hydroxy--methylheptan-2-one are then added. This mixture is stirred at about 25 C for 8 hours, poured into water, and this mixture is extracted with ether. The ethereal extracts are concentrated and the residue thus obtained is added to a 0.1 N solution of hydrochloric acid in aqueous acetone and stirred for 15 hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to yield a mixture of cis and trans 10-hydroxy-10- methylundec-S-en'Z-one which may be separated by fractional vacuum distillation or by preparative gas-liquid chromatography.

A mixture of 11.2 g. of diethyl carbethoxymethylphosphonate in 100 ml. of diglyme is treated with 2.4 g. of sodium hydride. This mixture is stirred until the evolution of gas ceases and 7.5 g. of trans lO-hydroxy-lO-methylundec-S temperature below 30 C. The mixture is stirred for 15 minutes and then diluted with water and extracted with ether. These ethereal extracts are washed well with water, dried over sodium sulfate and evaporated to remove the solvent. The residue is subjected to fractional vacuum distillation to yield cis, trans ethyl 3,7,11-trirnethyl-11-hydroxydrodeca-2,6- dienoate and trans, transethyl 3,7,11-trimethy1-ll-hydroxydodeca-2,6-dienoate.

By employing the cis isomer of lhydroxy-l0-methylundec--en-2-one in the foregoing procedure, there is obtained cis, cis ethyl 3,7,11-trimethyl-l 1-hydroxydodeca-2,o-dienoate and trans, cis ethyl 3,7,1 l-trimethyl-l1-hydroxydodeca-2,6- dienoate.

EXAMPLE 16 A solution of 20.9 g. of the ethylene ketal of methyl 3- bromopropyl ketone (obtained by treating the ketone with v ethylene glycol in benzene in the presence of p-toluenesulfonic acid) in 100 ml. of benzene is treated with 20 g. of triphenylphosphine. This mixture is heated at reflux temperatures for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo, and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until a red solution is obtained and 7.2 g. of 6-hydroxy-6-methylheptan-2-one are then added. This mixture is stirred at about 25 C for 8 hours, poured into water, and this mixture is extracted with ether. The ether extracts are combined, washed with water to neutrality, dried over sodium sulfate and reduced to dryness under vacuum. The residue, containing 2-ethylenedioxy-6,IO-dimethyl-lO-hydroxyundec- 2-ene, is added to 100 ml. of dry methanol containing 500 mg. of activated Spercent palladium-on-charcoal catalyst. The mixture is hydrogenated at room temperature until 1.05 equivalents of hydrogen have been taken up; then the mixture is filtered. over a bed of Celite diatomaceous earth. The filtrate is added to 250 ml. of benzene, washed with several portions of water, dried over sodium sulfate and evaporated to dryness under vacuum. The residue, containing the desired 2- ethylenedioxy-6,10-dimethylundecan-lO-ol, is added to a 0.1 N solution of hydrochloric acid in aqueous acetone and stirred for 15 hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to yield 10-hydroxy-6,10-dimethylundecan-Z-one which may be separated by fractional vacuum distillation or by preparative gas-liquid chromatography.

A mixture of 11.2 g. of diethyl carbethoxymethylphosphonate in 100 ml. of diglyme is treated with 2.4 g. of sodium hydride. This mixture is stirred until the evolution of gas ceases and 7.5 g. of 10-hydroxy-6,10-dimethylundecan- 2-one are then slowly added with stirring, maintaining a temperature below 30 C. The mixture is stirred for minutes and then diluted with water and extracted with ether. These ethereal extracts are washed well with water, dried over sodium sulfate and evaporated to remove the solvent. The residue is subjected to fractional vacuum distillation to yield cis ethyl 3,7,11-trimethyl-1 1-hydroxydodec-2-enoate and trans ethyl 3,7,1 l-trimethyhl 1-hydroxydodec2-enoate.

EXAMPLE 17 To a solution of 28.2 g. of trans, trans ethyl 3,7,11 trimethyl-l1-hydroxydodeca-2,G-dienoate and 250 ml. of dry ethyl acetate, 500 mg. of (4 percent) activated palladium-ontrimethyl-l l-hydroxydodec-Z-enoate which is purified by preparative scale gas-liquid chromatography.

Similarly, trans ethyl 3,7,11-trimethyl-l l-hydroxydodec-Z- enoate is prepared from trans, cis ethyl 3,7,1l-trimethyl-1lhydroxydodeca-2,6-dienoate.

EXAMPLE 18 By the procedure described in Example 17 the compounds listed under 11 are prepared from the respective compounds listed under 1.

l cis, trans 3,7,1l-trimethyl- 1 1-hydroxydodeca-2,6-dienoic acid cis, cis 3,7,ll-trimethyl-1lhydroxydodeca-2,6-dienoic acid trans, cis 3,7,11-trimethyl- 1 l-hydroxydodeca-2,6-dienoic acid trans, trans methyl 3,7,1 1- trimethyl-l l-hydroxydodeca- 2,6-dienoate trans, cis methyl 3,7,1 l-trimethyl-1 l-hydroxydodeca-2,6'- dienoate trans, cis propyl 3,7,1ltrimethyl-l l-hydroxydodeca 2,6-dienoate cis, cis isopropyl 3,7,11- trimethyl-l l-hydroxydodeca- 2,6-dienoate cis, trans hexyl 3,7,11- trimethyl-l l-hydroxydodeca- 2,6-dienoate trans, trans 3,7,1 l-trimethyl-l l-acetoxydodeca-2,6 dienoic acid cis, trans 3,7,114rimethyl- 1 l-trimethylacetoxy-2,6-dienoic acid trans, cis 3,7,1 l-trimethyl- 1 l-benzoxydodeca-2,-dienoic acid trans, trans 3,7,1 l-trimethyll 1-ethoxydodeca-2,6-dienoic acid cis, cis 3,7,1 l-trimethyl-l 1- butoxydodeca-2,6-dienoic acid cis, trans 3,7,1 l-trimethyll l-phenylethoxydodeca-2,fi-dienoic acid trans, cis 3,7,1 l-trimethyl-l lcthoxydodeca-2,6-dienoic acid trans, trans methyl 3,7,1 l-trimethyl-l1-methoxydodeca-2,6- dienoate cis, cis ethyl 3,7,1 l-trimethyl- 1 l-ethoxydodeca-2,o-dienoate cis, trans ethyl 3,7,1 l-trimethyl-l l-ethoxydodeca-2,6- dienoate trans, cis ethyl 3,7,1l trimethyl-l 1-ethoxydodeca-2,6- dienoate trans, trans ethyl 3,7,1 l-trimethyl-l l-ethoxydodeca-Z ,6- dienoate trans, trans butyl 3,7,11-tri methyl-1 l-(tetrahydropyran-Z- yloxy )dodeca-2,6-dienoate cis, trans hexyl 3,7,1 l-trimethyl-1 l-(tetrahydrofuran-Z- yloxy)dodeca-2,6-dienoate trans, trans hexyl 3,7,1 l-trimethyl-l l-propoxydodeca-2,6- dienoate cis, cis octyl 3,7,l1-trimethyl-1l-phenylethoxydodeca- 2,6-dienoate trans, trans ethyl 3,7,1 l-trimethyl-l l-acetoxydodeca-2,6- dienoate cis, trans ethyl 3,7,11-trimethyl-l 1-caproxydodeca-2,6- dienoate ll cis 3,7,1 ltrimethyl-l lhydroxydodec-Z-enoic acid cis 3,7,11-trimethyL11- hydroxydodec-Z-enoic acid trans 3,7,11-trimethyl-11- hydroxydodec-2-enoic acid trans methyl 3,7,1 l-trimethyl-l l-hydroxydodec-L enoate trans methyl 3,7,11-trimethyl-1l-hydroxydodec-Z- enoate trans propyl 3,7,1 l-trimethyl-l l-hydroxydodec-Z- enoate cis isopropyl 3,7,1 l-trimethyl-1 l-hydroxydodec-Z- enoate cis hexyl 3,7,11-trimethyl- 1 l-hydroxydodec-Z-enoate trans 3,7,1l-trimethyl-l lacetoxydodec-2-enoic acid cis 3,7,l1-trimethyl-11- trimethylacetoxy-Z-enoic acid trans 3,7,1 l-trimethyl-l lbenzoxydodec-Z-enoic acid trans 3,7,1l-trimethyl-1lethoxydodec2-enoic acid cis 3,7,1 l-trimethyl-l 1- butoxydodec-2-enoic acid cis 3,7,ll-trimethyl-l1- phenylethoxydodecQ-enoic acid trans 3,7,1l-trimethyi-1lethoxydodec-2-enoic acid trans methyl 3,7,11-trimethyl-1l-methoxydodec-2- enoate cis ethyl 3,7,1 l-trimethyl- 1 l-ethoxydodec-2-enoate cis ethyl 3,7,1 l-trimethyl- 1 1-ethoxydodec-2-enoate trans ethyl 3,7,1 l-trimethyll l-ethoxydodec-Z-enoate trans ethyl 3,7,1 l-trimethyl- 1 1-ethoxydodec-2-enoate trans butyl 3,7,1 l-trimethyll 1-( tetrahydropyran-Z-yloxy)- dodec-2enoate cis hexyl 3,7,11-trimethyl- 1 1-(tetrahydrofuran-Z-yloxy)- dodec-Z-enoate trans hexyl 3,7,1l-trimethyll l-propoxydodec-Z-enoate cis octyl 3,7,l1trimethyl- 1 1-phenylethoxydodec-Z-enoate trans ethyl 3,7,1 l-trimethyl- 1 l-acetozydodec-Z-enoate cis ethyl 3,7,1l-trimethyl- 1 l-caproxydodec-Z-enoate EXAMPLE 19 To a solution of 20.9 g. of the ethylene ketal of l-bromohexan-4-one (obtained by treating 1-bromo-4-hexanone with ethylene glycol in benzene in the presence of p-toluenesulfonic acid) in 100 ml. of benzene is added 20 g. of triphenylphosphine. This mixture is heated at reflux temperature for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until an orange solution is obtained and 3.8 g. of ethyl methyl ketone is then added. This mixture is stirred at about 25 C for about 8 hours, poured into water and this mixture is extracted with ether. The ethereal extracts are concentrated and the residue thus obtained is added to a 0.1 N solution of hydrochloric acid in aqueous acetone and stirred for about hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to yield a mixture of the cis and trans isomer of 7-methylnon-6-en-3- one which is separated by preparative gas-liquid chromatography into the individual isomers.

To a solution of 20.9 g. of the ethylene ketal of lbromopentan-4-one in 100 ml. of benzene is added g. of triphenylphosphine. This mixture is heated at reflux temperature for 2 hours and then filtered. The solid material thus collected is washed with benzene, dried in vacuo and added to 6.49 g. of butyl lithium in 50 ml. of dimethylsulfoxide. This mixture is stirred until an orange solution is obtained and 5.5 g. of cis 7-methylnon-6-en-3-one (the ketone obtained in Paragraph 1) is then added. This mixture is stirred at about C for about 8 hours, poured into water and this mixture is extracted with ether. The ethereal extracts are concentrated and the residue thus obtained is added to a 0.1 N solution of hydrochloric acid in aqueous acetone and stirred for about 15 hours. The mixture is then poured into ice water and extracted with ethyl acetate. After washing these extracts with water and drying them over sodium sulfate, they are evaporated to furnish a mixture of the trans, cis and cis, cis isomers of 6- ethyl-10-methyldodeca-5,9-dien-2-one which is separated by preparative gas-liquid chromatography to the individual isomers.

By repeating the above procedure with the exception of using trans 7-methylnon-6-en-3-one in place of cis 7-methylnon-6-en-3-one, there is obtained a mixture of the cis, trans and trans, trans isomers of 6-ethyl-10-methyldodeca-S ,9-dien- 2-onewhich is separated as described above.

Similarly, in the above procedure, instead of using either the trans or cis isomer of 7-methylnon-6-en-3-one as the starting material, there can be used a mixture of the isomers obtained in Paragraph 1 hereof in which case a mixture of the four isomers is obtained which can then be separated by preparative gas-liquid chromatography into the four isomers.

A mixture of 11.2 g. of diethyl carbethoxymethylphosphonate in 100 ml. of diglyme is treated with 2.4 g. of sodium hydride. This mixture is stirred until the evolution of gas ceases and 7.5 g. of trans, cis 6-ethyl-10-methyldodeca- 5,9-dien-2-one is then slowly added with stirring, maintaining a temperature below C. The mixture is stirred for about 15 minutes and then diluted with water and extracted with ether. These ethereal extracts are washed well with water, dried over sodium sulfate, and evaporated to remove the solvent to furnish a mixture of the trans,trans,cis and cis,trans,cis isomers of ethyl 3,1 1-dimethyl-7-ethyltrideca-2,6,IO-trienoate which is separated by preparative gas-liquid chromatography.

The above procedure is repeated three times with the exception of using cis, cis 6-ethyl-10-methyldodeca-S,9-dien-2- one as the starting material the first time; trans, trans 6-ethyl- 10-methylodeca-S,9-dien-2-one the second time; and cis, trans 6-ethyl-lO-methyldodeca-S,9-dien-2-one the third time to obtain the cis,cis,trans and cis,cis,cis; the trans,trans,trans and trans,trans,cis; and the cis,trans,trans and cis,trans,cis of ethyl 3,11-dimethyl-7-ethyltrideca-2,6,lO-trienoate, respectively. The isomers are separated by preparative gas-liquid chromatography.

EXAMPLE 20 2 grams of methyl 3,7,1 l-trimethyltrideca-2,6,10-trienoate in 50 ml. of anhydrous ether is added over a 30-minute period to a stirred suspension of 2 g. of lithium aluminum hydride in 50 ml. of anhydrous ether at -20 C under nitrogen. This mixture is stirred at 20 C for 15 hours and then cautiously treated with about 10 ml. of ethyl acetate and then about 4 ml. of water. The mixture is then filtered and the solid thus collected is washed well with ether. The ether solution is dried over sodium sulfate and evaporated to yield 3,7,1 l-trimethyltrideca-2,6,10-trien-1-o1.

The procedure of this example is repeated with the exception that methyl 3,7,11-trimethyltrideca-2,6,IO-trienoate is replaced with the esters preferably the methyl esters, described hereinabove, for example, those Examples 1 through 4 to furnish the corresponding free alcohol at C-l, for example, 3,7,11-trimethyldodeca-2,6,IO-trien-1-ol 3,11- dimethyl-7-ethyltrideca-2,6,IO-trien-l 3,7-diethyl-l lmethyltrideca-2,6,10-trien-1-o1, 3,1 1-dimethyl-7-ethyldodeca- 2,6,10-trien-l-o1, 7,1 1-dimethyl-3-ethyltrideca-2,6, 1 O-trien- 1-01, 7,11-dimethyl-3-ethylododeca-2,6,l0trien-1-o1, and the like.

Similarly, the C-lalcohol corresponding to the 2,6-diene, 1,10-diene and 2ene esters of Examples 8 through 17 are obtained by treatment with lithium aluminum hydride using the procedure of this example, for example,

3,7,1 1-trimethyldodeca-2,6-dien-l-ol,

3,7-dimethyl-1 1-ethyltrideca-2,10-dien- 1 01,

3,1 l-dimethyl-7-ethyltrideca-2,lO-dien-1-o1,

3 ,7-diethyl-l l-methyltrideca-2,10-dien-1-o1,

3,1 1-dimethyl-7 ethyldodeca-2,10-dien-l-o1,

3,7-diethyl-1 l-methyldodec-Z-en-l -o 1,

3,7,1 l-triethyltrideca-2,10-dien-l-ol,

3,7,1 l-trimethyltrideca-2,lO-dien-l-01, and

3,7,1 1-trimethyldodeca-2,6-dien-l ,1 l-diol from ethyl 3,7,1 1-trimethyldodeca-2,6-dienoate,

ethyl 3,7-dimethyl-1 l-ethyltrideca-Z,10-dienoate,

ethyl 3,1 1-dimethyl-7-ethyltrideca-2,IO-dienoate,

ethyl 3 ,7-diethyl-1 1 -methyltrideca-2, 1 O-dienoate,

ethyl 3,1 1-dimethyl-7-ethyldodeca-Z,10-dienoate,

ethyl 3,7-diethy1-1 l-methyldodec-l-enoate,

ethyl 3,7,1 l-triethyltrideca-2,IO-dienoate,

ethyl 3,7,1 1-trimethyltrideca-2,10-dienoate, and

ethyl 3,7,1 l-trimethyl-l l-hydroxydodeca-2,6-dienoate, respectively.

are obtained EXAMPLE 21 A mixture of l g. of 3,7,11-trimethyltrideca-2,6,lO-trien-l- 01, 4 ml. of pyridine and 2 ml. of acetic anhydride is allowed to stand at room temperature for 15 hours. The mixture is then poured into water and stirred. The mixture is extracted with methylene chloride and the organic extracts are dried and evaporated to yield 1-acetoxy-3,7,1l-trimethyltrideca- 2,6, l O-triene.

By repeating the above process using as the starting material, other C-l alcohols prepared hereinabove, the corresponding acetate is obtained, e.g. 1-acetoxy-3,7,1 l-trimethyldodeca-2 ,6,10-triene, l-acetoxy-3 ,l l-dimethyl-7-ethyltrideca-2,6,10-triene, 1-acetoxy-3 ,7-diethyl-1 l-methyltrideca-2,6,10-triene, 1acetoxy-3,1 l-dimethyl-7-ethyldodeca- 2,6, l O-triene, 1-acetoxy-7,1 1-dimethyl-3-ethyltrideca-2,6, l 0- triene, l-acetoxy-7,l l-dimethyl13-ethyldodeca12,6,l0- triene, and the like.

Similarly, by using other carboxylic acid anhydrides in the process of this example in place of acetic anhydride, for example, propionic anhydride, n-butyric anhydride, n-caproic anhydride, and the like, the corresponding l-acylates are obtained, e.g. l-propionate, l-butyrate, and the like.

EXAMPLE 22 28 grams of 3,7,11-trimethyltrideca-2,6,IO-trien-l-ol is added to a suspension of 3.0 g. of sodium hydride in 110 ml. of benzene, this mixture is stirred until the evolution of hydrogen ceases and then 47 g. of ethyl iodide is added with stirring. The mixture is refluxed for 2 hours and then washed with water. Evaporation of solvent in vacuo furnishes the ethyl ether of 3,7,11-trimethyltrideca-2,6,10-trien-1-o1 which is purified by chromatography.

Through the use of other alkyl halides, such as methyl iodide, propyl bromide, and the like, in place of ethyl iodide, the corresponding methyl ether, propyl ether, and the like, are obtained.

By repeating the process of this example with the exception of substituting other Cl alcohols in place of 3,7,1 l-trimethyltrideca-2,6,10-trien-l -o l e. g. 3 ,7,1 l-trimethyldodeca-2,6,10- trien- 1 -ol, 3 ,1 l-dimethyl-7-ethyltrideca-2 ,6,1 O-tn'en- 1 -ol 3 ,7-diethyl-l l-methyltrideca-2,6,10-trienl -o 1 and the like, the corresponding ether, methyl ether, propyl ether, and the like, are obtained.

EXAMPLE 23 a solution of 1.2 g. of methyl 3,7,1 l-trimethyltrideca- 2,6,10-trienoate in 5 ml. of dimethylsulfoxide is added to a solution of 1 equivalent of dimethylsulfoxonium methylide in dimethylsulfoxide [prepared by the procedure of Corey et al., J. Am. Chem. Soc. 87, 1353 (1965)]. The mixture is stirred under nitrogen and at room temperature for about 20 hours and then at 50 C for about 7 hours. 50 ml. of water is then added and the resulting mixture extracted 4 times with 50 ml. of ethyl acetate. The combined extracts are washed with water and saturated aqueous sodium chloride solution, dried and evaporated to furnish methyl 2,3-methylene-3,7,1l-trimethyltrideca-6,10-dienoate which is purified by silica chromatography.

By using as the starting material in the process of this exam ple, other 2,6,1 O-trienoates described herein (see Examples 1- 5, for example), there are obtained the corresponding 2,3- methylene-6,10-dienoates, e.g., methyl 2,3-methylene-3,7,1 1- tri-methyldodeca-6,IO-dienoate, methyl 2,3-methylene-3,l1- dimethyl-7-ethyltrideca-6,IO-dienoate, ethyl 2,3-methylene- 3,7,11-tri-methyldodeca-6,10-dienoate, ethyl 2,3-methylene- 3,1 1 dimethy1-7-ethy1trideca-6,10-dienoate, ethyl 2,3- methylene-3,11-dimethy1-7-ethylodedca-6,10-dienoate, ethyl 2,3 -m ethylene-3 ,7 ,1 1-trimethyl-trideca-6,IO-dienoate, ethyl 2,3-methylene-3-ethyl-7,1 1-dimethyl-trideca-6,10-dienoate, ethyl 2 ,3-methylene-3-ethyl-7, 1 l-dimethyl-dodeca-6, l 0- dienoate, ethyl 2,3-methylene-3,7-diethyl-1l-methyl-trideca- 6,10-dienoate, and the like.

By using as the starting material in the process of this example, the ethyl esters of Examples 8-17 and 19 and the esters of Example 18, the corresponding 2,3-methylene esters are obtained. For example,

ethyl 2,3-methylene-3,7,1 1-trimethy1dodec-6-enoate,

ethyl 2,3-methylene-3 ,7-dimethyl- 1 1 -ethyltridec-10- enoate,

ethyl 2,3-methylene-3,1 1-dimethyl-7-ethyltridec-l0- enoate,

ethyl 2,3-methylene-3 ,7-diethy1-l 1 -methyltridec-1 0- enoate,

ethyl 2,3-methylene-3 ,1 1-dimethy1-7-ethyldodec-10- enoate,

ethyl 2,3-methylene-3 ,7-diethyl-1 1 -methyldodec-1 0- enoate,

ethyl 2,3 -methylene-3 ,7-diethyl-l l-methyldodecanoate,

ethyl 2,3-methylene-3,7,1 1-triethyltridec-10-enoate,

ethyl 2,3-methylene-3,7,1 1-trimethyltridec-10-enoate,

ethyl 2,3-methylene-l 1-hydroxy-3,7,1 1-trimethy1dodec-6- enoate,

ethyl 2,3-methylene-3,7,l l-trimethyldodecanoate,

ethyl 2 ,3-methylene-7-ethyl-3 ,1 l-dimethyltridecanoate, and

' methyl ethyl 2,3-methylene-3,7,11-trimethyldodec-lO-enoate are obtained from the corresponding ethyl 2,6-dienoate, ethyl 2,10-dienoate and ethyl 2-enoate.

By subjecting the thus-prepared 2,3-methylene-2,6- dienoates to the procedures of Examples 6, 20, 21 and 22, the corresponding free acids, free alcohols, esters and ethers, respectively, are obtained, e.g., 2,3-methyIene-3,7,11- trimethyltrideca-6,10-dienoic acid, 2,3-methylene-3,7,l1- trimethyltrideca-6,l0-dien1-o1, 1-acet0xy-2,3 -methylene- 3 ,7,1 l-trimethyltrideca-6,IO-diene, 1-ethoxy-2,3-methy1ene- 3,7,1 l-trimethyltrideca-6,10-diene, and the like.

EXAMPLE 24 A mixture of 7 g. of methylene iodide and 3 g. of zinccopper couple in 15 ml. of anhydrous ether is heated at reflux under nitrogen for 3 hours. The mixture is then cooled and 2 g. of methyl 3,7,1l-trimethyltrideca-2,6,IO-trienoate added. This mixture is allowed to stand at room temperature for 2 hours and is then poured into 200 m1. of 2 percent aqueous sodium carbonate and extracted twice with ml. portions of ether. The extracts are dried over sodium sulfate and evaporated under reduced pressure. The oily residue is held at 0.01 mm. to remove any unreacted methylene iodide and then purified by gas-liquid chromatography to obtain methyl 6,7- methylene-3 ,7,1 1-trimethyltrideca-2,10-dienoate, methyl 10,1 l-methylene-3,7,1 1-trimethyltrideca-2,6-dienoate,

6,7;10,1 1-(bis)methylene-3,7,1l-trimethyltridec-Z- enoate.

By using the 2,3methylene compounds of Example 23 as the starting material in the above process, there is obtained methyl 2,3;6,7;10,1 1-(tris)methylene-3,7,1 l-trimethyltridecanoate, methyl 2,3 ;6,7-(bis)methy1ene-3,7,I 1- trimethyltridec-l l-enoate, and methyl 2,3;10,l 1- (bis)methylene-3,7,1 1-trimethyltridec-6-enoate, ethyl 2,3;6,7-(bis)methylene-3,7,1 l-trimethyldodecanoate, ethyl 2,3;10,1 1-(bis)methylene-3,7-dimethyl-1 l-ethyltridecanoate, ethyl 2,3;10,1 1-(bis)methylene-3,l1-dimethyl-7-ethyltridecanoate, ethyl 2,3;10,11-(bis)methylene-3,l l-dimethyl-7 -ethyldodecanoate, ethyl 2,3;10,1l-(bis)methylene-3,7- diethyl-1 l-methyldodecanoate, ethyl 2,3 1 O, 1 1- (bis)methylene-3,7,1 l-trimethyldodecanoate, and the like.

By repeating the procedure of this example using other alkyl esters described herein (e.g. Examples 1-5, 8-15 and 19), the corresponding methylene and (bis)methylene compounds are obtained. For example,

ethyl 10,1 1-methylene-3 ,7,1 1-trimethyldodeca-2,6- dienoate,

ethyl 6,7 l 0,1 1-bismethylene-3 ,7 ,l l-trimethyldodec-Z- enoate, and

ethyl 6,7 -methylene-3 ,7 ,1 1 -trimethyldodeca-2 l O-dienoate;

ethyl 10,1 1-methylene-3,1 1-dimethyl-7-ethyltrideca-2,6- dienoate,

ethyl 6,7-methylene-3 ,1 1-dimethyl-7-ethyltrideca-2, l 0- dienoate, and

ethyl 6,7;10,1 l-bismethylene-3,l 1-dimethyl-7-ethyltridec- 2-enoate;

ethyl 10,1 l-methylene-3,l l-dimethyl-7-ethyldodeca-2,6- dienoate,

ethyl 6,7-methylene-3,1 1-dimethyl-7-ethyldodeca-2,10-

dienoate, and

ethyl 6,7;10,1 l-bismethylene-3 ,1 l-dimethyl-7-ethyldodec- Z-enoate;

ethyl 10,1 l-methylene3 ,7-dimethyl-1 1-ethyltrideca-2,6- dienoate,

ethyl 6,7-methylene-3 ,7-dimethyl-1 1-ethyltrideca-2,10-

10,1 l-methylene-3,7,1 1-trimethyltrideca-2,6

ethyl 6,7;10,1 1-bismethylene-3,7,l l-trimethyltridec-2- enoate are obtained from ethyl 3,7,1 l-trimethyldodeca-2,6,IO-trienoate,

ethyl 3,1 1-dimethyl-7-ethyltrideca-2,6,IO-trienoate,

ethyl 3,1 1-dimethyl-7-ethyldodeca-2,6,lO-trienoate,

ethyl 3,7-dimethyl-1l-ethyltrideca-2,6,IO-trienoate, and

ethyl 3,7,1l-trimethyltrideca-2,6,IO-trienoate, respectively.

The corresponding acids can be obtained using the procedure of Example 6 and the corresponding saturated derivatives can be obtained by hydrogenation using the procedure of, for example, Example 7.

EXAMPLE 25 To a mixture of 2 g. of 3,1l-dimethyl-7-ethyltrideca-2,6,10- trien-l-ol in 150 ml. of methylene chloride at C, there is slowly added 1.0 molar equivalent of m-chloroperbenzoic acid in 100 ml. of methylene chloride. The resulting mixture is then allowed to stand for 15 minutes at 0 C and then washed with 2 percent aqueous sodium sulfite solution, with percent aqueous sodium bicarbonate solution and with water, dried over sodium sulfate and evaporated to an oil which contains a mixture of the 10,1l-epoxide, 6,7-epoxide and a small amount of the 6,7;10,l1-(bis)epoxide of 3,11-dimethyl-7-ethyltrideca- 2,6,10-trien-l-ol. This mixture is then purified and separated into the individual epoxides by chromatography on silica, i.e., 10,1 1-oxido-3,l 1-dimethyl-7-ethyltrideca-2,6-dien-l-ol, 6,7- oxido-3,l 1-dirnethyl-7ethyltrideca-2,10-dien-l-ol, and 6,7 l 0,1 l-(bis)oxido-3 ,l l-dimethyl-7-ethyltridec-2-en-1-ol.

By repeating the process of this example with the exception of using as the starting material other 2,6,10-trienes described herein, e.g., 1-acetoxy-3,1 l-dimethyL7-ethyltrideca- 2,6,l0triene, methyl ether of 3,1l -dimethyl-7-ethyltrideca- 2,6,lO-triene-l-ol, methyl 3,1l-dimethyl-7-ethyltrideca- 2,6,l0l-trienoate, methyl 3,7,1l-trimethyltrideca-2,6,l0- trienoate, methyl 3,7,11-trimethyldodeca-2,6,IO-trienoate, methyl 3,7-diethyl-l 1-methyltrideca-2,6,10-trienoate, 3,7,1 1- trimeth yltrideca-2,6, l O-trienoic acid, 3 ,7,1 1 -trimethyldodeca-2,6,10-trienoic acid, 3,11-dimethyl-7-ethyltrideca- 2,6,l0-trienoic acid 3,7-diethyl-1l-methyltrideca-2,6,l0- trienoic acid, 3,7-diethyl-1l-methyltrideca-2,6,lO-trien-l-ol, 3,7,1l-trimethyltrideca-2,6,IO-trien-l-ol, and the like, in place of 3,1l-dimethyl-7-ethyltrideca-2,6,IO-trien-l-ol, the corresponding 10,1l-epoxides, 6,7-epoxides and a small amount of the 6,7;10,1l-(bis)epoxides are obtained, e.g.,

l-acetoxy-l0,1 l-oxido-3,l1-dimethyl-7-ethyltrideca-2,6- diene,

methyl ether of 3,1l-dimethyl-7ethyl-l0,ll-oxidotrideca- 2,6-dien-l-ol methyl dienoate,

methyl 10,1 1-oxido-3,7,1 l-trimethyltrideca-2,6-dienoate,

methyl 10,1 l-oxido-3,7,l 1-trimethyldodeca-2,6-dienoate,

methyl 10,1 l-oxido-3,7-diethyl-l l-methyltrideca-2,6- dienoate,

10,1 l-oxido-3,7,1 l-trimethyltrideca-2,6-dienoic acid,

10,1 1-oxido-3,7,1 l-trimethyldodeca-2,6-dienoic acid,

10,1 1-oxido-3,l l-dimethyl-7-ethyltrideca-2,6-dienoic acid,

10,1 l-oxido-3,7-diethyl-l 1-methyltrideca-2,6-dienoic acid,

10,1 l-oxido-3,7-diethyl-l l-methyltrideca-2,6-dien-l-ol, 10,1l-oxido-3,7,ll-trimethyltrideca-2,6-dien-l-ol, and the like, and the corresponding 6,7-epoxide and 6,7;10,11(bis)epoxide.

By use of the procedure of this example, there is obtained,

ethyl 10,1 l-oxido-3,7,l 1-trimethyldodeca-2,6-dien0ate,

ethyl 6,7-oxido-3,7,l 1-trimethyldodeca-2,IO-dienoate, and

ethyl 6,7; 10,1 1-bisoxido-3 ,7,l l-trimethyldodec-2-enoate;

10,1 l-oxido-3,1 1-dimethyl-7-ethyltrideca-2,6-

ethyl 10,1 l-oxido-3,1 l-dimethyl-7-ethyltrideca-2,6- dienoate,

ethyl 6,7-oxido-3,l l-dimethyl-7-ethyltrideca-2,l0-

dienoate, and

ethyl 6,7;l0,l l-bisoxido-3,l 1-dimethyl-7-ethyltridec-2- enoate;

ethyl 10,1 l-oxido-3,l l-dimethyl-7-ethyldodeca-2,6- dienoate,

ethyl 6,7-oxido-3,l 1-dimethyl-7-ethyldodeca-2,l0- dienoate, and

ethyl 6,7;l0,l 1-bisoxido-3,l l-dimethyl-7-ethyldodec-2- enoate;

ethyl 10,1 l-oxido-3,7-dimethyl-l l-ethyltrideca-2,6- dienoate,

ethyl 6,7-oxid0-3,7-dimethyl-l l-ethyltrideca-2,10- dienoate, and

ethyl 6,7;10,l l-bisoxido-3,7-dimethyl-l l-ethyltridec-2- enoate;and

ethyl 10,1 1-oxido-3,7,l 1-trimethyltrideca-2,6-dienoate,

ethyl 6,7-oxido-3,7,l l-trimethyltrideca-2,IO-dienoate, and

ethyl 6,7;10,1 1-bisoxido-3,7,1 l-trimethyltridec-2-enoate from ethyl 3 ,7,1 l-trimethyldodeca-2,6, l O-trienoate,

ethyl 3,1 1-dimethyl-7-ethyltrideca-2,6,lO-trienoate,

ethyl 3,1 l-dimethyl-7-ethyldodeca-2,6,l0-trienoate,

ethyl 3,7-dimethyl-1 l-ethyltrideca-2,6,IO-trienoate, and

ethyl 3,7,1 1-trimethyltrideca2,6,IO-trienoate, respectively.

By use of the procedure of this example, the 2,3- methylenes, 6,7-methylenes, 10,11-methylenes, 2,3;6,7-bismethylenes and 2,3,10,11-bismethylenes of Examples 23 and 24 having unsaturation at C-6,7, C-10,11 or C-6,7;l0,l1 are converted into the corresponding mono and/or bis-epoxide. For example,

ethyl 2,3-methylene-10,l l-oxido-3,7,1 l-trimethyldodeca- 6-enoate,

ethyl 2,3-methylene-6,7-oxido-3,7,l l-trimethyldodec-IO- enoate, and

ethyl 2,3-methylene-6,7;l0,l l-bisoxido-3,7,l l-trimethyldodecanoate;

ethyl 2,3-methylene-10,1l-oxido-3,7,l 1-trimethyltridec-6- enoate,

ethyl 2,3-methylene-6,7-oxido- 3,7,11-trimethyltridec-10- enoate, and

ethyl 2,3-methylene-6,7;10,1 l-bisoxido-3,7,l l-trimethyltridecanoate;

ethyl 2,3-methylene-l0,1 l-oxido-3,l l-dimethyl-7-ethyltn'dec-6-enoate,

ethyl 2,3-methylene-6,7-oxido-3,1 l-dimethyl-7-ethyltridec- IO-enoate, and

ethyl 2,3-methylene-6,7;l0,l lbisoxido 3,11-dimethyl-7- ethyltridecanoate;

ethyl 10,1 lmethylene-6,7-oxido-3 ,1 1-dimethyl-7-ethyltridec-Z-enoate;

ethyl 6,7-methylenel 0,1 l-oxido-3 ,1 1-dimethyl-7 -ethyl- 10,1 1-methylene-3,l l-dimethyl-7-ethyltrideca-2,6-

enoate and ethyl 3,1 l-dimethyl-7-ethyl-l0,l l-oxidotridecanoate.

EXAMPLE 26 Anhydrous hydrogen chloride is introduced into 100 ml. of ether at C until a saturated solution is obtained. 1 gram of methyl 3,7,1l-trimethyltrideca-2,6,l0-trienoate is added and the resulting mixture is then allowed to stand at 0 C for 4 days. The mixture is then evaporated under reduced pressure to an oil which is purified by silica chromatography to furnish methyl 7,1 l-dichloro-3,7,l1-trimethyltridec-2-enoate.

Through the use of other 2,6,l0-triunsaturated compounds described herein as the starting material in the above process, the corresponding 7,1 l-dichloro derivatives are obtained, e.g., methyl 7,1 l-dichloro-3,7,l l-trimethyldodec-2-enoate, methyl 7,1 l-dichloro-3,l l7-ethyltridec-2-enoate, 7,1 ldichloro-3,7,1l-trimethyltridec-2-enoic acid, 7,1 l-dichloro- 3,7,1l-trimethyldodec-2-enoic acid, 7 ,1 l-dichloro-3,1 ldirnethyl-7-ethyltridec-2-enoic acid, and the like.

By use of the above procedure, there is prepared ethyl 7,1 ldichloro-3,7,1 1-trimethyldodec-2-enoate, ethyl 7,1 1- dichloro-3,11-dimethyl-7-ethyltridec-2-enoate, ethyl 3,1 l-

dichloro-3 ,1 l-dimethyl-7-ethyldodec-2-enoate, ethyl 7 ,l 1- dichloro-3 ,7-dimethyl-l l-ethyltridec-Z-enoate, and ethyl 7 ,1 1-dichloro-3 ,7 ,l l-trimethyltridec-2-enoate from ethyl 3,7,1 1-trimethyldodeca-2,6,lO-trienoate, ethyl 3,1 l-dimethyl- 7-ethyltrideca-2,6,IO-trienoate, ethyl 3,1l-dimethyl-7-ethyldodeca-2,6,l0-trienoate, ethyl 3,7-dimethyl-ll-ethyltrideca- 2,6,10-trienoate, and ethyl 3,7,11-trimethyltrideca-2,6,l0- trienoate, respectively.

Similarly, by using the 2,3-methylene-6,l0-dienoates of Example 23 as the starting material in the procedure of this example, the corresponding 7,1l-dichloro compounds are obtained. For example, ethyl 7,1l-dichloro-2,3-methylene-3,l ldimethyl-7-ethyltridecanoate and ethyl 7,l1-dichloro-2,3- methylene-3,7,1l-trimethyldodecanoate from ethyl 2,3- methylene-3,l l-dimethyl-7-ethyltrideca-6,lO-dienoate and ethyl 2,3-methylene-3,7,11-trimethyldodeca-6,IO-dienoate, respectively.

7,11-Dichloro compounds having saturation at C-2,3 are prepared from the corresponding 6,10-diene compound or by hydrogenation of 7,1l-dichloro-2-ene compounds using the procedure of Example 7.

EXAMPLE 27 Chlorine gas is bubbled into 200 ml. of carbon tetrachloride at 0 C until a 0.5 molar solution is obtained. 25 grams of methyl 3,7,11-trimethyltrideca-2,6,lO-trienoate is added and the mixture is then stirred and allowed to stand at 0 C for 24 hours. The mixture is then evaporated to furnish an oil containing methyl 10,11-dichloro-3,7,1 1-trimethyltrideca-2,6- dienoate, methyl 6,7-dichloro-3,7,1 1-trimethyltrideca-2,l0- dienoate and methyl 6,7,l0,1l-tetrachloro-3,7,ll-trimethyltridec-Z-enoate which are purified and separated by gas-liquid chromatography or alternatively purification and separation can be made by 2 distillations through a spinning band fractionation column.

The above process is repeated with the exception of using as the starting material other 2,6,10-triunsaturated compounds described herein in place of methyl 3,7,1 l-trimethyltrideca- 2,6,10-trienoate, e.g. methyl 3,7,1l-trimethyldodeca-2,6,10- trienoate, methyl 3,1 l-dimethy1-7-ethyltrideca-2,6,10- trienoate, 3,7,1 l-trimethyltrideca-2,6,10-trienoic acid,

. 3,7,1 1'trimethyldodeca-2,6,10-trienoic acid, 3,1 1-dimethy1-7- ethyltrideca-2,6,lO-trienoic acid, 3,7,l1-trimethyltrideca- 2,6, l O-trien- 1 -01, 3,7,1 l-trimethylodeca-2,6, l O-trien- 1 -ol, 3,1 l-dimethyl-7-ethyltrideca-2,6,10-trien-l-ol, l-acetoxy- 3,7,1 1-trimethyltrideca-2,6,l0-trien, l-acetoxy-3,7,1 1- trimethyldodeca-2,6, l O-triene, l-acetoxy-3,l 1-dimethyl-7- ethyltrideca-2,6,lO-trien, 1-acetoxy3,l l-dimethyl-7-ethyltrideca-2,6,lO-triene, 1-methoxy-3,7,l l-trimethyltrideca- 2,6, l O-triene, 1-methoxy-3,7,l 1-trimethyldodeca-2,6,l0-

trien, l-methoxy-3,1 l-dimethyl-7ethyltrideca-2,6,IO-triene, and the like, and there are obtained the corresponding 10,1 1- dichloro derivatives, 6,7-dichloro derivatives and 6,7,10,11- tetrachloro derivatives, e.g. methyl l0,ll-dichloro-3,7,11- trimethyldodeca-2,6-dienoate, methyl 6,7-dichloro-3,7,lltrimethyldodeca-2,lO-dienoate, methyl 6,7,lO,l ltetrachloro- 3,7,1l-trimethyldodec-2-enoate, and the like. The C- 1 alcohol, l-acetoxy and l-methoxy compounds also furnish C- 2,3 dichloro derivatives which can be separated by chromatography.

By repeating the above procedure using ethyl 3,7,11- trimethyldodeca-2,6,IO-trienoate, ethyl 3,11-dimethyl-7- ethyltrideca-2,6,IO-trienoate, ethyl 3,1 l-dimethyl-7-ethyldodeca-2,6,l0-trienoate, ethyl 3,7-dimethyl-l l-ethyltrideca- 2,6,l0-trienoate and ethyl 3,7,11-trimethyltrideca-2,6,l0- trienoate, respectively, as the starting material, the corresponding ethyl 10,1l-dichloro-2,6-dienoate, ethyl 6,7- dichloro-2,l0-dienoate and ethyl 6,7,l0,ll-tetrachloro-2- enoate derivatives are obtained.

By repeating the procedure outlined in this example except for substituting bromine for chlorine, a mixture of the corresponding brominated compounds is prepared and separated by chromatography.

Use of a mixed halogen reagent, such as chlorine-fluorine in this procedure provides the corresponding mixed dihalo compounds.

In like manner, the corresponding 6,7-dibromo; l0,lldibromo; and 6,7,10,1l-tetrabromo derivatives of starting compounds ethyl 3,7,1 l-trimethyltrideca-2,6,lO-trienoate and ethyl 3,1l-dimethyl-7-ethyltrideca-2,6,lO-trienoate are prepared.

EXAMPLE 28 Ethyl 3,7,1l-trimethyl-l0,ll-oxidododeca-2,6-dienoate is prepared as described in Example 25 and is thereafter treated by the procedure of Example 27 to afford ethyl 3,7,1 1- trimethyl-6,7-dichloro- 10,1 l-oxidododec-Z-enoate. By repeating this procedure with those compounds not containing the a, B-unsaturated carbonyl system, the corresponding 6,7- dichloro-l0,ll-oxido derivative is separated from. the final reaction mixture by chromatography from the presence of some of the corresponding 2,3,6,7-tetrachloro-l0,l l-oxido compound. 7

Similarly obtained are ethyl 3,7,1l-trimethyl-6,7-dichloro- 10,1 l-oxidotridec-Z-enoate and ethyl 3,1 l-dimethyl-6,7 dichloro-7ethyl-l0,l l-oxidotridec-Z-enoate as well as the corresponding methyl esters thereof.

EXAMPLE 29 The process of Example 27 is repeated with the exception that methyl 10,1 l-oxido-3,7,l 1-trimethyltrideca-2,6-dienoate is employed as the starting material in place of methyl 3,7,1 1- trimethyltrideca-2,6,lO-trienoate and there is obtained methyl 6,7-dich|oro-l0,113,7,11-trimethyltridec-2-enoate which can be purified by chromatography or fractional distillation.

By substituting other 10,1l-oxido-2,6-diunsaturated compounds described herein as the starting material in this example, e.g. methyl 10,1 l-oxido-3,7,1 l-trimethyldodeca-2,6- dienoate, methyl l0,ll-oxido-7-ethyl-3,ll-dimethytrideca- 2,6-dienoate, 10,1 l-oxido-3,7,l l-trimethyltrideca-2,6-dien- 101, 10,1 l-oxido-3,7,1l-trimethyldodeca-2,6-dien-1-ol, 10,1 l-oxido-3,11-dimethyl-7-ethyltrideca-2,6-dien-1-ol,

10,1 1-oxido-l-acetoxy-3,7 ,1 l-trimethyltrideca-2,6-diene, 10,1 l-oxido-l-acetoxy-3,7,l l-trimethyldodeca-2,6-diene, I 0,1 l-oxido-1-acetoxy-3, l 1-dimethyl-7-ethyltrideca-2,6-

diene, 10,1 l-oxido-l-methoxy-3,7,1 l-trimethyltrideca-2,6- diene, 10,1l-oxido-l-methoxy-3,7,ll-trimethyldodeca-2,6- diene, 10,1 1-oxido-l-methoxy-3,l l-dimethyl-7-ethyltrideca- 2,6-diene, 10,1 l-oxido-3,7,l 1-trimethyltrideca-2,6-dienoic acid, 10,11-oxido-3,7,11-trimethyldodeca-2,6-dienoic acid, 10,1 l-oxido-3,l 1-dimethyl-7-ethyltrideca-2,6-dienoic acid,

3] and the like, the corresponding 6,7-dichloro-10,ll-oxido compounds are obtained, e.g. methyl 6,7-dichloro-l0,1loxido-3,7,l l-trimethyldodec-2-enoate, methyl 6,7-dichloro- 10,1 1-oxido-7ethyl-3,l l-dimethyltridec-2-enoate, 6,7- dichloro-10,11-oxido-3,7,1l-trimethyltridec-Z-en-l-ol, 6,7- dichloro-10,l1-oxido-3 ,7 ,l l-trimethydodec-Z-en- 1 -ol, and

the like.

EXAMPLE 30 Anhydrous hydrogen chloride is bubbled into 100 ml. of carbon tetrachloride at C until a saturated solution is obtained. 1 gram of methyl 3,7,11-trimethyltrideca-2,6,10- trienoate is added and the resulting mixture is then allowed to stand at 0 C for 4 days. Then the mixture is evaporated under reduced pressure to an oil which is purified by column chromatography to furnish methyl l1-chloro-3,7,l l-trimethyltrideca-2,6-dienoate. B The process of this example is repeated with the exception of substituting other 2,6,10- trienoates prepared hereinabove, e.g. those of Examples 2-5, for the starting material and there is obtained the corresponding 1l-chloro-2,6-dienoate, for example methyl ll-chloro- 3,7,11-trimethyldodeca-2,6-dienoate, methyl 1l-chloro-3,1ldimethyl-7'-ethyltrideca-2,6-dienoate, methyl l1-chloro-3,7- diethyl-l l-methyltrideca-2,o-dienoate, and the like, ethyl 1 lchloro-3,7,1l-trimethyltrideca-2,6-dienoate, ethyl ll-chloro- 3,7,1 1-trimethyldodeca-Z,6-dien0ate, and the like.

By repeating the process of this example with the exception of substituting the corresponding 2,6,10-trienoic acids prepared hereinabove, (see, for example, Example 6) as the starting material in place of the 2,6,l0-trienoate employed above, the corresponding 1 1-chloro-2,6-dienoic acids are obtained, e.g. 1l-chloro-3,7,l l-trimethyltrideca-2,6-dienoic acid, 1l-chloro-3,7,11-trimethyldodeca-2,6-dienoic acid, 11- chloro-3,l1-dimethyl-7-ethyltrideca-2,6-dienoic acid, 11- chloro-3,7-diethyl-11-methyltrideca-2,6-dienoic acid, 1 lchloro-3,ll-dimethyl-7-ethyldodeca-2,6-dienoic acid, 11- chloro-7,ll-dimethyl-3-ethyltrideca-2,6-dienoic acid, 11- chloro-7,1 1-dimethyl-3-ethyldodeca-2,6-dienoic acid, and the like.

EXAMPLE 31 lnto a solution of 5 g. of methyl 10,1 l-oxido-3,7,l ltrimethyldecanoate (obtained by hydrogenation of the corresponding A 10,1 l-epoxide on 5 percent Pd/C) in 100 ml. of CCl is slowly bubbled hydrogen fluoride at 0 C with stirring. When about 1 chemical equivalent has been added, the mixture is allowed to stand for 6 hours, washed with water and evaporated to an oil which is chromatographed on silica to give methyl 10-hydroxy-l l-fluoro-3,7,l l-trimethyltridecanoate and methyl 10-fluoro-1 l-hydroxy-3,7,1ltrimethyltridecanoate.

By substituting in the above process as the starting material methyl 10,1 l-oxido-3,7, l l -trimethyItrideca-2,-dienoate, there is obtained the corresponding IO-hydroxy-l l-fluoro and IO-fluoro-l l-hydroxy derivatives containing a fluoro atom at position C-7.

The process of this example is repeated with the exceptions that 0.1 N hydrogen fluoride in anhydrous methanol is used as the reagent and reaction medium and the reaction is run for 3 days at room temperature and there is. obtained the corresponding substitution product IO-fluoro-l l-methoxy derivative. Use of other lower monohydric alcohols as the reaction medium provides the corresponding alkoxy derivatives.

To 5 grams of methyl lO-hydroxy-l l-fluoro-3,7,l ltrimethyltridecanoate in 100 ml. of anhydrous ether, is added 1 chemical equivalent of diazomethane. 1 drop of boron/trifluoride is then added and the reaction mixture is allowed to stand at 0 C for 1 hour and then at room temperature for 2 additional hours. Thereafter, the mixture is washed with water, evaporated and chromatographed to give methyl lO-methoxy-l l-fluoro-3,7,1 l-trimethyltridecanoate.

By use of other diazoalkanes, such as diazoethane, the corresponding alkoxy derivatives are prepared, such as the 10- ethoxy compounds.

EXAMPLE 32 A. To a solution of 2 g. of methyl 7,1l-dichloro-3,7,l1- trimethyltridec-Z-enoate in anhydrous ether 50 ml.) at 0 C is added with stirring lithium aluminum hydride (0.36 g.). After 1 hour, acetic acid (2.4 ml.) is added. The mixture is washed with ice water and the ether phase dried and evaporated to give 7,1l-dichloro-3,7,1l-trimethyltridec-Z-en-l-ol.

By using other 7,1l-dichloro esters (see Example 26, for example), the corresponding C-l alcohols are obtained.

By the procedure of Example 21, the above C-l alcohols are converted into the corresponding acylates, e.g. acetates.

By the procedure set forth in paragraph 4 of Example 31, the above C-l alcohols are converted to the corresponding ether.

B. Likewise, the alkyl ll-monochloro 2,6-dienoates, e.g. methyl 11-chloro-3,7,ll-trimethyltrideca-2,o-dienoate, and the like (see Example 30), are converted by the processes of Part A above to the corresponding ll-chloro-l-hydroxy, l1- chloro-l-acyloxy and l l-chloro-l-alkoxy derivatives.

EXAMPLE 33 The procedure of Example 30 is repeated using other C- 10,1 1 unsaturated compounds described herein such as those of Examples 8-14, 23 and 24 to obtain the corresponding 11- chloro-derivatives, e.g. ethyl l 1-chloro-3,l l-dimethyl-7-ethyltrideca-2,6-dienoate, ethyl 1l-chloro-2,3-methylene-3,7,1l-

trimethyldodec-o-enoate, ethyl l 1-chloro-3,l 1-dimethyl-7- ethyldodec-2-enoate, ethyl 11-chloro-2,3;6,7-bismethylene- 3,7,1 l-trimethyldodecanoate, and the like.

EXAMPLE 34 1 gram of trans, trans ethyl 3,7,1l-trimethyl-ll-hydroxydodeca-2,6-dienoate in 8 ml. of pyridine and 2 ml. of triethylamine is treated with 1 ml. of acetyl chloride. This mixture is allowed to stand for 15 hours at about 25 C and is then poured into ice water and extracted with methylene chloride. These extracts are washed well with water, dried over sodium sulfate and evaporated to yield trans, trans ethyl 3,7,1 1- trimethyl-l l-acetoxydodeca-2,6-dienoate.

Use of other acid chlorides, such as trimethylacetyl chloride, benzoyl chloride, phenylacetyl chloride, and the like, yields the corresponding esters.

EXAMPLE 35 A. lnto a mixture of 2 g. of methyl l0,1l-oxido-3,7,lltrimethyltridec'a-Z,6-dienoate in ml. of ether, there is introduced a slow stream of hydrogen chloride for 1 hour at 0 C. The mixture is then allowed to stand at 0 C for 18 hours. Then the mixture is washed with 5 percent aqueous sodium bicarbonate solution, dried over sodium sulfate and evaporated to an oil containing methyl 1 l-chloro-lO-hydroxy- 3,7,11-trimethyltrideca-2,6-dienoate and methyl 7,11- dichloro-10-hydroxy-3,7,11-trimethyltridec-2-enoate which are purified and separated by preparative silica chromatography.

B. The process of Part A above is repeated with the exception of using as the starting material methyl 6,7-oxido-3,7,1ltrimethyltrideca-2,lO-dienoate and there is obtained methyl 7-chloro-6-hydroxy-3 ,7,1 l-trimethyltrideca-2,10-dienoate and methyl 7,1l-dichloro-6-hydroxy-3,7,l l-trimethyltridec-Z- enoate.

C. By repeating the process of Example 34 with the exception of using methyl l1-chloro-10-hydroxy-3,7,1l-trimethyltrideca-2,6-dienoate or methyl 7,1l-dichloro-lO-hydroxy- 3,7,1l-trimethyltridec-2-enoate as the starting material, the corresponding IO-acylatesare obtained, erg. methyl llchloro-l0-acetoxy-3,7,1 1-trimethyltrideca-2,6-dienoate,

Claims (12)

1. 2. A compound according to claim 1 of the formula:
2. 3. A compound according to claim 2 wherein each of R1, R2, R3 and R4 is methyl or ethyl and R'' is hydrogen or lower alkyl.
3. 4. A compound according to claim 3 wherein each of R1, R2 and R3 is methyl; R4 is methyl or ethyl; R'' is lower alkyl; and Z7 taken together with Z6 is a carbon-carbon double bond.
4. 5. The compound, methyl 10,11-methylene-3,7,11-trimethyltrideca-2,6-dienoate, according to claim 4.
5. 6. A compound according to claim 3 wherein each of R1 and R3 is methyl; each of R2 and R4 is ethyl; R'' is lower alkyl; and Z7 taken together with Z6 is a carbon-carbon double bond.
6. 7. A compound according to claim 1 of the formula:
7. 8. A compound according to claim 7 wherein each of R1, R2, R3 and R4 is methyl or ethyl.
8. 9. A compound according to claim 8 wherein Z7 taken together with Z6 is a carbon-carbon double bond and Z11 taken together with Z10 is a carbon-carbon double bond.
9. 10. A compound according to claim 9 wherein each of R1, R2 and R3 is methyl and R4 is methyl or ethyl.
10. 11. A compound according to claim 10 wherein R'' is hydrogen, methyl or ethyl.
11. 12. A compound according to claim 9 wherein each of R1 and R3 is methyl and each of R2 and R4 is ethyl.
12. 13. A compound according to claim 8 wherein Z11 taken together with Z10 is the group