United States Patent 1191 [11] Patent Number: 4,940,831 Drake et a1. [45] Date of Patent: Jul. 10, 1990 [54] PURIFICATION OF CIS OLEFINS OTHER PUBLICATIONS [75] Inventors: gharlfs A‘ Drake’ Nowafa; Jlm D‘ “Chemistry and Biochemistry of Plant Pigments”, yerls’ silelven D‘ Bndges’ both of Goodwin, Academic Press, New York, 1965, p. 496. I - Bart esvl 6’ all of Okla‘ “Comprehensive Organic Chemistry”, Pergamon Press, [731 Asslgnee: Phillips Petroleum Company, New York, V01. 3, pp. 320-322. Bartlesvlne, Ok1a~ “Sul?nic Acid Catalyzed lsomerization of Ole?ns”, J_ Org. Chem. 41: p. 791 (1976). [21] Appl, 1510,; 312,103 “The Reaction Between Sulfochlorides and Or , ganomagnesium Halides”, Gilman et al, pp. 3501-3508, [22] Filed- Feb 15 1989 NW‘ 1929' ' ' ’ “The Constitution of Some Bacterial Casotenoids and their Bearing on Biosynthetic Problems”, Jensen, 1962, [51] Int. Cl.5 .............................................. .. C07C 7/17 p. 106. [52] US. Cl. .................................. .. 585/836, 558855386668, Primary ExaminerwGlenn C 31 darola [58] Field of Search ............. .. 585/833, 836, 856, 866, Ammey’ Agent’ 0’ F’""_Ha1 Brant w°°dr°w 585/868, 324 [57] ABSTRACT A method for purifying a cis-ole?n formed by alkylat [56] References Cited ing a sulfonate ester comprising mixing the reaction U_S_ PATENT DOCUMENTS formed by alkylatinga sulfonate ‘ester with an acid 3 ’ 444261’ 5/1969 Caprioli et al ‘ -------------- " 585/809 resuS°I“§1°“;S°P?,““§g an pun 1ca ion sad to :0“:no W1$915103’ a 1- 33‘‘ 4a 3min? co 0 an‘hf; (13/1970 Ga?“ et a1‘ "" " 585/811 X optionally a base follpowed by separation and distilla , , /1982 Szantay et a1. .. 424/84 tion or assin .d t. t th h .1. 4,609,498 9/1986 Banaslak e161. 260/4109 R ’ P 5 Sa‘ “8° 1°“ m“ ‘"9 "mg a 811” 4,673,672 6/1987 Houlihan et a1. ........ .. 514/95 gel and collectmg the “$916511 fractm 4,740,627 4/1988 Byers et al. 568/4699 4,749,818 6/1988 Byers et al. ....................... .. 585/324 22 Claims, N0 Drawings 4,940,831 1 2 (b) separating said acid solution from said ?rst puri? PURIFICATION OF CIS-OLEFINS cation mixture to.form a ?rst puri?cation product, (0) mixing said ?rst puri?cation product with a FIELD OF THE INVENTION C1-C4 alcohol to form a second puri?cation mix This invention relates generally to the puri?cation of ture, cis-ole?ns. (d) separating said C1-C4 alcohol from said second puri?cation mixture to form a second puri?cation BACKGROUND OF THE INVENTION product, and (e) distilling said second puri?cation product to yield Cis-ole?ns are an important source of pharmacologi cal and biological compounds such as pheromones. a third puri?cation product containing said cis-ole ?n. Unfortunately, the synthesis of cis-ole?ns is a very dif? cult and expensive process because of the tendency of In accordance with another embodiment of the pres ent invention, we have also discovered a process the reaction products to isomerize into inactive or inhib for the puri?cation of a cis-ole?n formed by alkyl itory trans-isomers. An example of a simple cis-ole?n ating a sulfonate ester wherein said cis-ole?n is which has proven dif?cult to produce economically is puri?ed from a reaction mixture formed by the cis-9-tricosene, a house?y pheromone. alkylation of said sulfonate ester, which process Many of the more classical syntheses require the use comprises of alkynes or Wittig reagents to obtain the desired cis (a) passing said reaction mixture through a suitable stereochemistry. Although these reagents produce cis chromatographic gel packed in an organic solvent ole?ns in high purity, their use in large scale production and of pure cis-ole?ns is prohibitively expensive. Many (b) recovering the organic fraction containing said cis-ole?ns, however, could be economically produced cis-ole?n. in high yields via a synthesis process which uses sulfo nate esters, if a method could be developed to avoid DETAILED DESCRIPTION isomerization from cis- to trans-isomers during the puri In accordance with one embodiment of this invention ?cation of the cis-olefm product. For instance, we have a process is provided for the puri?cation of a cis-ole?n discovered that cis-9-tricosene (and many other cis-ole formed by alkylating a sulfonate ester, wherein said ?ns) can be synthesized by a simple three step process cis-ole?n is puri?ed from a reaction mixture formed by beginning with readily available cis-alcohols. The ?rst the alkylation of said sulfonate ester, which process step of this process is to deprotonate the cis-ole?nic comprises alcohol to form a lithium or sodium alkoxide salt fol (a) mixing said reaction mixture with an acid solution lowed by reacting the ole?nic alkoxide salt to form a to form a ?rst puri?cation mixture, sulfonate ester, then alkylating the sulfonate ester with (b) separating said acid solution from said ?rst puri? an appropriate alkylmagnesium compound and a eu 35 cation mixture to form a ?rst puri?cation product, prous salt. After alkylation it is usually desirable to (0) mixing said ?rst puri?cation product with a recover the cis-ole?n in a highly puri?ed form. Most C1-C4 alcohol to form a second puri?cation mix schemes for puri?cation of the cis-ole?n rely on a distil ture, lation process. Unfortunately the cis-ole?n is substan (d) separating said C1-C4 alcohol from said second tially converted to a trans-ole?n during distillation from puri?cation mixture to form a second puri?cation the alkylating reaction mixture containing the sulfonate product, and ester. (e) distilling said second puri?cation product to yield It would also be advantageous if a process for the a third puri?cation product containing said cis-ole puri?cation of cis-ole?ns formed by alkylating a sulfo ?n. nate ester could be developed which is economical, 45 One suitable method of forming a cis-ole?n utilizing a simple, and easy to scale-up. sulfonate ester synthesis consists of It is an object of this invention to provide an econom (a) the deprotonation of a cis-ole?nic alcohol to form ical process for the puri?cation of cis-ole?ns produced a lithium or sodium salt followed by by alkylating a sulfonate ester. (b) the formation of a sulfonate ester and It is also an object of this invention to provide a sim 50 (c) the alkylation of the sulfonate ester with an alkyl ple, easy to scale-up process for the puri?cation of cis magnesium compound and a cuprous salt. ole?ns formed by alkylating a sulfonate ester. To produce a cis-ole?n, one need only begin with a It is a further object of this invention to provide a cis-ole?nic alcohol having a hydroxyl-group at the process for the puri?cation of cis-9-tricosene, which is desired site or sites of alkylation and choose an appro produced by alkylating a sulfonate ester. 55 priate alkylmagnesium compound having the desired Other aspects, objects, and several advantages of this alkyl group. invention will be apparent from the speci?cation, in Appropriate cis-ole?nic alcohols for use in the three cluding the examples and accompanying claims. step synthesis set forth above are non-conjugated, non cumulated, non-enolic (without a double bond adjacent SUMMARY OF THE INVENTION to a hydroxyl group) cis-ole?nic alcohols. The cis-ole In accordance with the present invention, we have ?nic alcohols can also contain more than one double discovered a process for the puri?cation of a cis-ole?n bond. A cis-ole?nic alcohol with more than one double formed by alkylating a sulfonate ester, wherein said bond can be employed with a double bond allylic to the cis-ole?n is puri?ed from a reaction mixture formed by hydroxyl group if the allylic double bond position is the alkylation of said sulfonate ester, which process inconsequential in the ?nal cis-ole?n, because said al comprises lylic double bond may shift position. Although cis-ole (a) mixing said reaction mixture with an acid solution ?nic allylic alcohols may be suitable for this process, to form a ?rst puri?cation mixture, they are not recommended because of the tendency for 4,940,831 3 4 allylic bonds to shift with the resultant isomerization to sulfonyl halide and alkoxide, but will generally be that trans-ole?nic alcohols. The cis-ole?nic alcohols can time period needed for the reaction to reach substantial also include glycols and polyols, however, each hy completion before the next step is begun, which time droxyl may serve as a site of alkylation. period has been found to be about 1 hour. Preferably the The ?rst step in this three step synthesis of a cis-ole?n reaction time is in the range of fromabout 1 hour to is a deprotonation reaction of a cis-ole?nic alcohol with about 24 hours. a source of an alkali metal ion selected from the group The third step in the three step synthesis of a cis-ole consisting of lithium and sodium ions. The ?rst reaction ?n is the reaction of the second reaction product with product comprises an alkoxide which can be formed an alkylmagnesium compound and a cuprous salt to utilizing reagents and techniques well known to those of 10 form a third reaction product comprising a cis-ole?n. skill in the art. Suitable sources of alkali metal ions The alkylmagnesium compound may be selected from include, but are not limited to, alkali metal ion sources the group consisting of dialkylmagnesium and alkyl selected from the group consisting of sodium metal, magnesium halide wherein the halide of said alkylmag lithium metal, alkyllithium, alkylsodium, aryllithium, nesium halide is selected from the group consisting of and arylsodium.