RESEARCH
Costly Odors from Terpenes Ozonization paves conven ient p a i n s to n e w p e r f u m e s a n d aromatics
1 3 6 ACS NATIONAL MEETING Organic Chemistry
Today's perfume chemist, like t h e alchemist of old, is concerned largely with trying to turn abundant, low-cost materials into rare and valuable prod ucts. Latest transmutation: Chemists at Givaudan Corp. have learned how to make cheap, locally-available ter penes into valuable new and known perfumes and aromatic chemicals. Rose, spicy-hay, violet, and a m b e r types of aromatics can all be synthe sized from terpenes and sesquiterpenes, Givaudan's Dr. H. E. Eschinazi told the Division of Organic Chemistry. Products range from relatively inex pensive citronellol ( major rose aro matic ) all the way up to costly irone (constituent of orris root and violet) and patchoulione (ambergris). These new synthetic routes drasti cally slash the costs of main' of these perfume products—from more than $200 per p o u n d to about S10 to S15 per pound in some cases, h e says. "Moreover, they assure a stable, do mestic source of these chemicals, ' Or. Eschinazi says. At present the trade d e p e n d s primarily on imports of natural essential oils for these materials, and many are in short supply from time to time. Ozonization is the common denom inator in each of the syntheses. In the citronellol route, the Givaudan chem ists ozonize 3-p-menthene to give ex cellent yields of the ketoaldehyde, 3,7dimethyl-6-oxo-octanal. Hydrogéna tion, followed by dehydration, gives citronellol as a mixture of citronellol rhodinol ( isopropylidene and isopropenyl forms), Or. Eschinazi says. Another common terpene, l-/)-methene, provides an easy access via ozoni zation tn rose and spicv-hav aromatic chemicals, according to Dr. Eschinazi. With ozone the terpene goes to the 3-isopropyl-6-oxoheptanal, is cyclohydrated through an internal aldol con 52
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densation in t h e presence of acids or bases, and winds u p as methyl ( 4-isopropv l-cyelopenten> 1 > ketone with a p l e a s a n t , spicy-hay odor. Hydrogéna tion of the k e t o n e with copper chromite c a t a l y s t at 150 C. yields t h e roselinalool t y p e alcohol 1-( 3-isopropylc y d o p e n t x 1 )-l -ethanol, he told the or ganic chemists. ► Five Steps to Irone. An improved synthesis of irone ( 6-methylionone) s t a r t i n g with cK-pinene lops three steps off t h e 8-step irone synthesis reported b y Hoffman-La Roche in 1957, accord ing t o the Givaudan chemist. It starts with ozonization of α-pinene which gives pinonic a l d e h y d e in 65 to 7 0 ' / yields. Refluxing t h e aldehyde in the p r e s e n c e of palladium catalyst produces the n e w ketone, pinonone, in 8 0 ' ^ yield. T h e ketone then reacts with s o d i u m acetylide in liquid ammonia to form the 3-(2,2,3-trimethyleyclobutyl )but-l-yn-3-ol in quantitative yield. W h e n h e a t e d in the presence of e t h y l a c e t o a c e t a t e , this butynol goes to 2-( 2 , 2 , 3 - t r i m e t h \ lc\ clobutN 1 )-hepta-2,4-dien-6-one in a yield of about 6 5 r r . T h e dienone—a cyclobutyl isomer of irone, d u b b e d cyclobutirone—is finally converted to irone via carbonium in t e r m e d i a t e s b y prolonged contact with p h o s p h o r i c acid, h e reports. T h e synthesis of a sesquiterpene ketone, a costly m e m b e r of the» valu able amber type aromatic chemical family, w a s also reported by Dr. Eschinazi. T h e item—patchoulione, a relative of patchouly alcohol whose structure was established by Dr. Bi'ichi and Dr. Erickson of MIT. Again, the s c h e m e involves the use of ozone. T h e s e s q u i t e r p e n e , β-patehoulene, is treated with ozone and t h e reaction mixture passed t h r o u g h a chromatographic col u m n (silica a l u m i n a ) . The product is the crystalline patchoulione, which has an ambergris-like odor, he reports. T h e significance of this work is two fold, Dr. Eschinazi says. First, yields of t h e k e t o a l d e h y d e s formed b y the ozonization of cycloalkenes are high, and these aldehydes constitute very useful a n d reactive intermediates in or g a n i c chemistry. T h u s , the work opens a n e w field of action in the search for c h e a p routes to synthesize new prod ucts for the perfume and p h a r m a c e u t i cal industries. Secondly, the work adds to t h e g r o w i n g importance of ozone as a r e a g e n t in organic chemistry, rather t h a n as just a laboratory curiosity, he concludes.
New Fîuorokeîaîs Highly Stable They c a n also serve as block ing a g e n t s to tie up active h y d r o g e n functions during reactions
1 3 6 ACS NATIONAL MEETING Organic Chemistry
A new family of ketals—a-fhioroketone ketals—made their debut be fore the Division of Organic Chemistry. T h e new products have good thermal and chemical stability and show prom ise as high-boiling, heat-stable liquids and, chemically, as blocking agents to tie u p active hydrogen functions dur ing reactions. Key to the new ketals is a novel basepromoted reaction, according to Dr. Douglas YY. Wiley a n d Dr. Howard E. Simmons of Du P o n t s central research department. in «-fluoroketones, the presence of the highly electronegative fluorine atoms enhances the Lewis acid character of the carbonyl group so that the i sol able hem i ketals can be obtained, Dr. Wiley explains. Since the hemiketal is quite acidic, it can be alkylated much the same as a phenol, h e says. Ketals of unfluorinated ketones nor mally are produced by acid-catalyzed reactions with alcohols or ortho esters. As contrasted with unfluorinated ketals, which are easily hydrolyzed, the new fluoroketone ketals are completely inert toward standard acid reagents. This holds even with concentrated sul furic acid at 180° C , the D u Pont chemists say. And this chemical and thermal stability is even more evident in the related cyclic ketals. Cyclic ketals are readily synthesized b y treat ing a fluoroketone with a halohydrin and base, they point out. T h e new ketals show unusual thermal properties, stand up to prolonged expo sure to high temperatures. At reflux they are stable to oxidation by atmos pheric oxygen for more than a week. And metals such as copper, zinc, and steel have little or no effect on the n e w products over the same period and un der the same conditions, according to the Du Pont men.
