THE CHEMICAL WORLD THIS WEEK Co. since Southern's incorporation during 1931. T h e Lake Charles, La., plant has been operated by Southern Alkali since 1947. Built by the Government during t h e w a r years for the production of magnesium metal, the Lake Charles facility was leased by Southern Alkali from W a r Assets Corp. and converted to the electrolytic p r o d u c tion of caustic soda and chlorine.
vision located at 2502 Robinhood Rd., Houston, Tex. Principal products of the company are a line of mastics for spe cialized uses in corrosion control, indoor and outdoor insulation, and as a vapor barrier where paint is not satisfactory.
MEWS B i t l E F §
Pacific Vegetable Oil Corp. has ac quired 8 0 % of the stock of California Flaxseed Products Co., Los Angeles firm specializing in manufacture of processed oils for the paint and varnish industry. T h e acquired firm will b e operated as a sub sidiary of Pacific Vegetable.
Du Pont Co.'s $30 million experimental station addition at Wilmington, Del., will be dedicated at ceremonies May 10. United Lacquer Mfg. Corp. is con structing a new explosionproof factor) building for a d d e d production of protec tive finishes and industrial coatings. T h e facilities are in Linden, N. J., along with the firm's h e a d q u a r t e r s . Earl Paint Corp. of Utica, Ν. Υ., has opened a southwest division. W . B. Pickard, Jr., is manager of this new service di-
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Rust Engineering Co. has been engaged as engineer-constructor of the new phos phate chemical plant being built near Mul berry, Fla., by the phosphate division of International Minerals & Chemical Corp.
Brown Co. manufacturer of Solka-Floc, moved its general sales offices on April 23 to 150 Causeway St., Boston 14, Mass. Optical Film Engineering Co., formerly located at 2125 Cherry St., Philadelphia, have announced the removal of their gen eral offices and factory to 2731 North Sixth St., Philadelphia 33, Pa.
Bethlehem Mercury Oxifier
W i t h this combination you can scien tifically clean mercury to the mostexacting standards. The type " P * Filter effectively removes floating impurities and acid residues. The Oxifier r e moves dissolved base metals. Al&houg h either can be used separately, i t is rec ommended they be used as a unit f o r maximum efficiency. Both are: avail able i n smaller and larger si:ze$ t o meet all requirements. Prices $80 to $725 per set V/rite today for details*
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Total Synthesis of Natural Steroid Precursor Announced A N N O U N C E M K M of the first total syn*** thesis of a complete steroid has aroused considerable interest in the chemi cal world. T h e process was worked out by a team of Harvard scientists h e a d e d by Robert B. Woodward, and some 20 steps are involved in the actual b u i l d - u p ard, Jr., is manager ot this new service diof the complex molecule, officially n a m e d DL - methyl - 3 - keto - 4,9 ( 11 )16 - etiocholatrienate. W o o d w a r d ' s work consti tutes the first synthesis of a so-called sat urated steroid whose composition contains three double bonds and four isomeric centers. Full details of the synthesis were presented by Dr. W o o d w a r d in giving t h e annual Centenary Address before t h e Chemical Society in London last week. Starting material for the synthesis was 2 - methyl - 5 - methoxy - 1,4-benzoquinone which eventually becomes ring C of t h e steroid. T h e actual steps involved can b e described as stereospecific in that every intermediate has been formed with exact spatial characteristics in mind. No u n usual synthetic steps are involved, t h e build-up being simply a very clever a p plication of known organic syntheses by which certain radicals are m a d e to attach themselves to the starting molecule until the desired steroid molecule is finally achieved. T h e present results obtained by W o o d w a r d are t h e product of a group effort over a period of 16 months.
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Dr. W o o d w a r d is another of t h e pres ent-day chemists to take u p the problem of total synthesis of steroids. In 1939, the late W e r n e r E. Bachmann was able to synthesize equilenin starting with a tetrahydrophenanthrene prepared from Cleve's acid. Since Russell E . Marker, in 1938, had converted equilenin to es trone by reduction, the total synthesis of both equilenin and estrone was considered accomplished. These compounds differ irom Woodward's steroid in that the A and Β rings in equilenin and the A ring in estrone are aromatic. T h e newly syn thesized steroid has three double bonds in the C - 4 , - 9 ( l l ) and -16 positions (see d i a g r a m ) . T h e r e is an additional angular methyl group in the new steroid at the C-10 position which is not found in equil enin and estrone. DL-Methyl-3-keto-4,9( 11 ) ,16etiocholatrienate
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The Synthesis T h e actual synthesis begins with ring C, the benzoquinone. With a Diels-Alder
MAY
7,
1951
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THE CHEMÎCAL WORLD THIS WEEK reaction, b u t a d i e n e is a d d e d to form a six-membered temporary ring D . By d e hydration and a zinc-dust reduction, the former quinone ring is converted into a cyclohexenone. T h e next step is the addition of vinyl ethyl ketone in the presence of a base which forms the nucleus of ring B. In the presence of more base and then with osmium tetroxide oxidation, ring Β is closed and two hydroxy 1 groups are a d d e d to ring D. T h e diol is pro tected by the formation of an acetone ketal, and the double bond b e t w e e n C - l l and -12 is removed by partial hydrogénation. T h e C-6 position is protected by formylation followed by condensation with methylaniline. In the next step, the ring A structure is started at C-10 on ring Β by reaction with acrylonitrile in the presence of a base. T h e resultant p r o d u c t consists of diastereomeric forms, and all further steps are carried out on one or t h e DI.- mixtures after separation. Following this, the nitrile is hydrolyzed to an acid which is then cyclyzed to an enol lactone. Treat ment of this with methyl G r i g n a r d reagent produces a methyl ketone which closes ring A by simple aldolization. T h e acetone ketal is converted into a d i a l d c h y d e , with opening of the temporary ring D . by cleav age with periodic acid. T h e synthesis is completed with a reaction in which the aldehyde is converted into a methyl ester by oxidation and esterification. T h e re sultant racemic mixture is the W o o d w a r d steroid. T h e steroid has been identified by use of infrared spectrum and shown to have the same structure as a conversion product of compound F. This latter steroid is optically active b u t identical in all other respects with W o o d w a r d ' s optically in active steroid mixture. It must be pointed out that infrared spectra do not distin guish b e t w e e n stereoisomers or mixtures thereof, but in this case the necessary proof of the steroid's desired character regardless of η or L configuration is as sured. According to Paul D. Bartlett, spokes man for Dr. W o o d w a r d , the present re search is now at the point ot resolving the steroid racemic mixture into its optic ally active components. Following this the research will be c o n t i n u e d with t h e definite idea of producing naturally active substances. O n e of the problems which will h a v e to be solved in order to pro duce cortisone, for example, is the elimi nation of the unsaturation of the steroid rings. Cortisone has only one double bond, located in ring A, t w o fewer than t h e W o o d w a r d steroid. Not Cortisone Dr. W o o d w a r d c a u t i o n e d that t h e steroid is not cortisone nor any other medical substance, a l t h o u g h he plans to continue his research a n d a t t e m p t t h e synthesis of natural steroids. "Since steroids are transformable o n e into an
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other." he explained in a L o n d o n inter view/* this opens the prospect of a pos sible conversion of present synthetic ster oid into cortisone or other steroids. But w e haven't done it yet," he emphasized, "and it will take a lot of hard work to do it. I don't know how many operations will be required before we get cortisone, nor how long it will take. It may even be impossible," h e said. With the present cortisone shortage, news of any kind in this field of steroid synthesis brings much speculation on the possibility of obtaining the valuable drug. Present supplies of cortisone are obtained from ox bile and available quantities of this starting material are not large enough to meet current d e m a n d s . T h e Research T e a m Collaborating with Dr. W o o d w a r d in the research which was carried out in Harvard's Converse laboratory, w e r e F r a n z Sondheimer, David T a u b , Karl Hensler, and W . M. M c L e m o r e . T h e group was aided by A. K. Bose, and D o r o t h y Voitle a n d Irving Osvar gave technical assistance. Large amounts ot starting materials w e r e provided by the Monsanto Chemical Co., a n d by Merck & Co.; the latter also pro
vided the original financial support ior the project. T h e research was further s u p p o r t e d by a grant from t h e Research C o r p of N e w York. D u r i n g a year of t h e work. Dr. W o o d w a r d was relieved of his regular teaching duties by appoint ment as the D u Pont research professor for 1 9 4 9 - 5 0 . In a c c o r d a n c e with Harvard's long s t a n d i n g policy, any practical results in t h e field of medicine which may ultimately come from this work will be administered in the public interest a n d will not be available exclusively to any one m a n u facturer. In this case, this will be effected t h r o u g h the administration and nonex clusive licensing of the p a t e n t s by t h e Re search C o r p . Dr. W o o d w a r d has m a d e contributions to t h e chemistry of quinine, patulin, strychnine, and other important c o m p o u n d s in the past. D u r i n g the W o r l d W a r II, he was a consultant of t h e committee on m e d i c a l research of the Office of Scientific Research and D e v e l o p m e n t , working es pecially on t h e penicillin project. W i t h William E. Doering of C o l u m b i a Uni versity, he devised and accomplished the first total synthesis of quinine in 1944. Me has recently been promoted to pro fessor of chemistry at Harvard.
RESEARCH
Sinclair Plan Offers Unusual O p p o r t u n i t y to Inventors n p H E facilities of Sinclair Research L a b -*• oratories, a multimillion dollar research plant at Harvey, 111., are b e i n g o p e n e d to "any American with an idea for a new or better petroleum p r o d u c t or applica tion," said P. C. Spencer in a n n o u n c i n g details of the Sinclair plan. Cited as a way to meet t h e nation's critical n e e d s , the plan will provide a m e a n s of r e m o v ing a major obstacle to i n v e n t i v e n e s s lack of proper financial a n d research facili ties. Mr. Spencer pointed out t h a t in our early days an a m a t e u r m e c h a n i c or scientist could invent and prove a device in his garage as did F o r d , Edison, and the Wright brothers. T o d a y , however, a man and an idea are no longer enough to move our technological machine. Two other factors are needed—facilities and money. T h e Sinclair plan is specifically designed to bring these a n d t h e m a n to gether. T h e research plant at Harvey was built with an eye to the future. A l t h o u g h Sin clair has a n u m b e r of i m p o r t a n t projects under way, t h e potential capacity of t h e laboratories is greater t h a n c u r r e n t r e quirements. T h e Sinclair plan proposes to make a portion of this capacity avail
CHEMICAL
able to i n d e p e n d e n t inventors for research and d e v e l o p m e n t . I d e a s will be invited from inventors e v e r y w h e r e . T h e success of t h e plan, therefore, d e p e n d s on finding every American without available facilities who has an idea for a new or better petroleum p r o d u c t , or for its improved application. Theses people will be invited to submit to the laboratories any ideas they may have for better petroleum products, with the provision that every idea submitted b e first protected by a p a t e n t application or a p a t e n t . This provision is in the interest of t h e inventor as well as of t h e labora tories. T h e directors of t h e c o m p a n y labora tories will select from submitted ideas those which show the most promise, t h e n u m b e r b e i n g d e t e r m i n e d by t h e labora tories' available capacity at t h e time. W h e n an idea is selected, Sinclair will m a k e , in most cases, an a r r a n g e m e n t with the inventor w h e r e b y t h e c o m p a n y will receive the privilege of using t h e inven tion free of royalties in return for t h e in vestment of money, time, facilities, and personnel. T h i s in n o w a y impairs t h e inventor's opportunity to sell his idea in
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