substituents are replaced with heteroaromatic groups, the antitumor ac tivity decreases. If the substituents are a- or β-naphthyl, potency is retained. The Lilly scientists found the carbamoyl group to be essential for antitumor activity. The nitrogen substituents on the carbamoyl group can be varied greatly while still maintaining the activity. These varia tions include compounds where the N-substituents are hydrogen, Nmethyl, N-allyl, N-propynyl, N,N-dimethyl, and compounds where the substituents with the nitrogen forms a pyrrolidine ring. The N-phenyl de rivative, however, is much less ef fective.
Indene analog is potential drug
152ND
ACS NATIONAL MEETING Medicinal Chemistry
Dr. T. Y. Shen and his coworkers have synthesized 1 -p-chlorobenzy lideny 1-5methoxy-2-metnylindene-3-acetic acid, an indene analog of indomethacin. The scientists at Merck Sharp & Dohme (Rahway, N.J.) found that the cis analog has anti-inflammatory activity nearly the same as indometha cin. The trans isomer, however, is only one fifth as active. For the synthesis of the indene isostere, 6-methoxy-2-methyl-l-indanone was condensed with ethyl bromo-
acetate under Reformatsky conditions to give the hydroxy intermediate. This intermediate was readily de hydrated by acid to ethyl 5-methoxy2-methyl-3-indenyl acetate. The indenyl acetate was condensed with p-chlorobenzaldehyde in the presence of base to give the 1-p-chlorobenzylidene derivative. Of the two geo metrical isomers of the derivative, as a result of the steric hindrance of the 2-methyl group, the isomer with the two phenyl groups cis to each other forms as the predominant product. Dr. Shen's new analog is isosteric with indomethacin. Unlike N-acyl indoles, it is stable under acidic and alkaline conditions. 62 C&EN SEPT. 19r 1966
U(IV) reduces cleanly in molten fluorides
152ND
ACS NATIONAL MEETING Analytical Chemistry
Reduction of uranium (IV) at a plati num electrode is a reversible, oneelectron process in a mixture of lithium, beryllium, and zirconium fluorides at 500° C. This conclusion is based on a study of the electro chemical reduction and oxidation of uranium (IV) undertaken at Oak Ridge National Laboratory by Dr. Gleb Mamantov (of the University of Tennessee) and D. L. Manning. The study was carried out in two molten fluoride solvents—64-34-1.8 mole % and 65-29-5 mole % lithium fluoride-beryllium fluoride-zirconium tetrafluoride. (The second solvent is the one used for uranium tetrafluoride in molten salt reactor experiments.) Dr. Mamantov and Mr. Manning studied the behavior of uranium (IV) in these solvents by linear sweep voltammetry, chronopotentiometry, and chronoamperometry at tempera tures between 480° and 620° C. They obtained well-defined and re producible voltammograms and chronopotentiograms at uranium tetra fluoride concentrations as high as 0.8 mole c/o. These results provide the basis for an in situ electroanalytical method for the determination of uranium in molten fluorides, the sci entists say. Dr. Mamantov and Mr. Manning ran a series of linear-sweep voltam mograms at different scan rates for the reduction of uranium (IV) at a platinum wire electrode. The peak currents obtained yielded a straight line when plotted against the square root of the scan rate. This plot indi cates that the redox reaction is a simple charge-transfer reaction. The results also show that at scan rates faster than 2 volts per minute dif fusion is the predominant mass-trans fer process. Diffusion coefficients. From the linear-sweep voltammograms, the ORNL workers calculated the diffusion coefficient of uranium ( I V ) , which varies from 1.6 Χ 10~6 cm. 2 per second at 480° C. to 4 Χ 10~6 cm. 2 per second at 600° C. From a plot of the logarithm of the diffusion co efficient against the reciprocal of tem perature, they obtained 10.5 kcal. per mole as the activation energy for dif fusion of uranium (IV). Analysis of the chronopotentiogram for the reduction of uranium (IV) at a vertical platinum plate electrode shows that the reduction is a reversi
ble, one-electron process. The chronopotentiometric and voltammetric results also indicate that disproportionation of uranium (III) at 500° C. does not take place to an appreciable extent under the condi tions of the experiment.
Nitrate ion oxidizes cycloheptatriene
152ND
ACS NATIONAL MEETING Organic Chemistry
When cycloheptatriene is oxidized by eerie ammonium nitrate, evidence points to the nitrate ion (free or complexed) as being the oxidizing agent. The finding suggests that other oxida tions involving metal ions are possibly anion oxidations, the metal ions reoxidizing the reduced anions, says Iowa State University's Dr. Walter S. Trahanovsky. Cycloheptatriene's oxidation prod ucts are benzaldehyde, benzene, and carbon monoxide. Dr. Thahanovsky and his coworker, L. Brewster Young, note that when the eerie ammonium nitrate oxidation is carried out in an hydrous acetonitrile, benzaldehyde is produced. Dr. Trahanovsky contends that formation of benzaldehyde when this solvent is used demands that the nitrate ion be involved in the oxida tion of cycloheptatriene because the oxygen atom of the benzaldehyde can only come from the nitrate ion. The Iowa State University workers also find that when the eerie am monium nitrate oxidation is carried out in a variety of solvents of dif ferent basicity, the ratio of benzalde hyde to benzene end products changes only slightly. For example, in 50 r/c aqueous acetic acid, the ratio is 78 to 22. In anhydrous acetoni trile, the ratio is 76 to 24. Dr. Tra hanovsky argues that the insensitivity of the benzaldehyde-to-benzene ratio to solvent basicity suggests that a coordinated nitrate ion acts as a base during formation of benzalde hyde. Cyclic transition states involving ligands of a metal ion have been pro posed for other oxidation reactions such as the oxidation of alcohols to ketones by chromium (VI), Dr. Trahanovsky points out. However, experimental support for such transi tion states has been lacking up to now. Dr. Trahanovsky and Mr. Young believe that these proposals are more reasonable in the light of their findings. Complicated scheme. Dr. Traha novsky puts forward a somewhat complicated scheme to show how eerie ammonium nitrate oxidizes cy-
