ACS President Cairns With great reluctance
patent reform embodied in the Administration bill. "Due to the nature of the American chemical industry," Dr. Cairns said, "there will be a race to the Patent Office to file the preliminary applications provided for in S. 1042." This will create many new problems for chemists, will result in the hasty filing of incompletely conceived disclosures, and goes too far in penalizing a diligent prior inventor who, because of the complexity of his invention, requires time to define it properly before filing an application. The ACS modification to the firstto-file proposal, Dr. Cairns told the committee, will result in patent applications being filed earlier than they are now, but will correct inequities in patent ownership and deficiencies in patent disclosures. The Administration has already backed the ACS compromise as "a reasonable modification" if a modification is needed (C&EN, Jan. 29, page 17). Another section of S. 1042 to come under ACS fire is one that would require applications to be published before the Patent Office may have found that they contain patentable subject matter. Dr. Cairns says that publication should be delayed until some patentable matter has been found because: • It often takes several years to establish a clear technical definition of many complex chemical inventions to complete patent disclosures and determine proper claims. • The proliferation of chemical literature which may be redundant or trivial can only dilute the value of that which is worthwhile. • Publication of material, later found to be unpatentable, would rein20 C&EN FEB. 5, 1968
force a tendency to conceal inventions as trade secrets. ACS, therefore, recommends that publication occur only after the finding of allowable subject matter. ACS takes no position on the controversial question of the patentability of inventions involving computer programs. S. 1042 declares such material to be unpatentable. However, Dr. Cairns points out, the definition of computer programs in the bill needs to be clarified. As it stands, it appears to prohibit patents on any chemical process ordinarily carried out with automated equipment. ACS supports a section of S. 2597, a bill generally supported by the American Bar Association, which would make importation of a product produced in a foreign country by a process patented in the U.S. an infringement of the U.S. patent. However, ACS strongly opposes one section of this bill that would deny the right of chemists, who are qualified but are not admitted to the bar, to represent inventors in preparing and prosecuting patent applications. Today's technology requires that people with strong backgrounds in chemistry or other disciplines be allowed to help inventors, Dr. Cairns said.
coworkers Dr. B. C. Clark, Jr., Dr. Jean-Claude Farine, Donald D. Denson, and Clyde E. Bishop first prepare either the di- or triperoxide of any of various cyclic ketones. These ketones include cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, and others. The Georgia group forms the dimeric or trimeric peroxide by reacting the cyclic ketone with a 34% hydrogen peroxide solution at room temperature. As long as the peroxide precursors can be prepared, with or without substituted groups on the ketone ring, almost any macrocyclic compound can be synthesized, Dr. Story says. They then irradiate or heat the peroxide precursors to form directly a mixture of a cyclic hydrocarbon and a lactone. In addition, the reaction regenerates ketone starting material. Photolysis involves irradiating a 4% solution of the peroxide in methanol or benzene with a 450-watt lamp for about three hours. Thermolysis involves heating the peroxide in an evacuated, sealed ampoule at 150° C. for about 30 minutes or, alternatively, running it through a continuous gas chromatograph in a variety of columns at 180° C. In some cases, photolysis gives the best reaction yields; in other cases, thermolysis does. As an example, the
General synthesis prepares macrocyclic compounds easily "Preparing any of these macrocyclic compounds is incredibly simple," says University of Georgia's Paul R. Story in describing his new general synthesis of large single ring compounds, now tediously prepared. By mild photolysis or thermolysis of a suitable cyclic ketone peroxide Dr. Story obtains good yields of macrocyclic hydrocarbons and lactones containing as many as 23 carbon atoms in the ring. "We're aiming for a hundred," he says. The procedure makes certain macrocyclic compounds available for the first time, particularly those with odd numbers of carbon atoms. It simplifies the route to others now made by the more difficult acyloin condensation of long straight-chain compounds. Moreover, since the method uses easily prepared peroxides of such inexpensive starting materials as 18 cent-per-pound cyclohexanone, it promises economic advantages to the perfume industry in synthesizing various musk compounds, Dr. Story explains. For example, dihydroambrettolide—a 16-carbon ring c o m p o u n d now costs about $280 per pound. In their procedure [/. Am. Chem. Soc, 90, 817 ( 1 9 6 8 ) ] , Dr. Story and
Mild conditions give good yields of macrocyclics
0^.0^
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Trimeric cyclohexanone peroxide
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Cyclohexanone Cyclohexam
photolysis of trimeric cyclohexanone peroxide yields 15% cyclopentadecane, 25% 16-hexadecanolactone, and 20% regenerated cyclohexanone. However, thermolysis of the same peroxide yields 16% cyclopentadecane, only 1% of the 16-hexadecanolactone, and 15% regenerated ketone. This lactone, known as dihydroambrettolide, is an important musk compound valued for its odiferous and fixative properties. Dr. Story is continuing work on synthesizing substituted macrocyclic compounds such as muskone. The Georgia chemist is also studying use of this synthesis to prepare antibiotic macrolides.
Air-pollutant-polymer reactions defined by Clarkson research Probable reaction mechanisms stemming from air-pollutant-polymer interactions were spelled out last week at the Third Middle Atlantic Regional Meeting of the American Chemical Society in Philadelphia, Pa., by Dr. Hans H. G. Jellinek of Clarkson College of Technology, Potsdam, N.Y. Dr. Jellinek says that chain scission, cross-linking, and reactions at the side groups of the polymers are major effects of such interactions with nitrogen dioxide and sulfur dioxide. The reactions, he says, lead to changes in molecular weight, thus affecting physical properties. The reaction which takes place at the side groups of various polymers is one which incorporates fragments of the pollutants along the polymer chain. Dr. Jellinek and his coworkers, Dr. F. Flajsman, F. Kryman, and Dr. Y. Toyoshima, exposed several types of polymer films (20 microns thick) to nitrogen dioxide and sulfur dioxide. This thickness was used to eliminate diffusion as a rate-controlling process, Dr. Jellinek points out. After exposure, the order of stability of the various polymers was roughly the same as their stability during thermal oxidation; these are, in descending order: branched polyethylene, polypropylene, polystyrene, polymethylmethacrylate, and polyacrylonitrile. Of the two classes of polymers—saturated and unsaturated—the unsaturated are more sensitive to nitrogen dioxide. Their sensitivity in this case is comparable to their sensitivity to ozone, the Clarkson scientist explains. From this point, the Clarkson team concentrated on polystyrene, which, Dr. Jellinek points out, has good filmforming properties and is fairly stable. Moreover, its thermal degradation in vacuum, ultraviolet, and via oxidation
had been studied previously. There were no complications due to crosslinking, at least not when exposed to nitrogen dioxide alone. When polystyrene was exposed to nitrogen dioxide, a random chain scission took place which proceeded roughly proportional to the nitrogen dioxide pressure. In addition, a number of abnormalities occurred, especially at the beginning of the reaction. The reaction slows down after a few hours, accelerates again, and then eventually slows down a little (but less than before). Infrared measurements demonstrated that nitrogen dioxide is incorporated in the form of nitro and nitriate groups along with backbone of the polystyrene molecule. This reaction, Dr. Jellinek notes, apparently passes through a maximum as a function of time. Thus, while the nitro groups accumulate, the polymer molecules become polar and subsequently behave differently in benzene solution than they did before. In other words, because of aggregation, the intrinsic viscosity—a function of molecular weight—cannot be determined in benzene. However, straight-line curves are obtained in a polar solvent, such as dioxane. The Clarkson scientists also studied the reaction as a function of temperature, thereby determining the Arrhenius parameters. From this point, the reaction mechanism was determined and all of the experimental data were accounted for, according to Dr. Jellinek. As to the significance of these findings, Dr. Jellinek notes that it's of great economic importance to know about the adverse effects of air pollutants on polymers (coatings, textiles, building materials, paints, and the like). It's also important to know the fundamental reactions involved. Only then, the Clarkson scientists point out, can rational preventive measures be taken.
FDA, medicine library to test Wiswesser Line Notation Soon to be transferred to magnetic tape are data relating to some 20,000 chemicals now card indexed at the Food and Drug Administration and the National Library of Medicine. A key to the operation will be the Wiswesser Line Notation ( W L N ) system of denoting molecular structures. FDA and NLM cite two main objectives of the program. One is to assess the merits of WLN for encoding structural formulas. The other is to draw up data on the cost and effectiveness of using this computerized
Programming Services' Horner at Work Ardent proponent
method of searching out information relating to chemical structure, and to compare the findings with like data for other retrieval systems. "There's no doubt in my mind that W L N will show up very favorably, says J. Kenneth Horner, chemical information specialist with Programming Services, Inc., in Palo Alto, Calif., and an ardent proponent of the Wiswesser notation system. The recent activity surrounding WLN suggests that this view is shared by others who regard the computer as the only practical means of storing and retrieving the enormous amount of chemical information. Examples: •Programming Services is encoding into W L N four issues of Index Chemicus. This pilot study may lead to the Institute for Scientific Information's selling a taped version of notations for structures and related details of the new chemicals that appear each week in its publication. • Four companies, Hoffmann-LaRoche, Winthrop Laboratories, G. D. Searle, and Dow Chemical are sharing in a cooperative information exchange program that involves use of WLN to encode chemical structures contained in the U.S. patent literature. • A revision of the manual that describes how the notation system works is due out shortly. William J. Wiswesser, a chemist at Ft. Detrick, Md., began formulating his linear notation system in 1950. His aim was to devise a method to depict the structure of a molecule uniquely and unambiguously, a goal he shared in common with others who were working independently on coding systems of their own. He combed through structural data FEB. 5, 1968 C&EN
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