substituents are replaced with heter-oaromatic groups, the antitumor ac­tivity 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 varia­tions include compounds where the N-substituents are hydrogen, N-methyl, N-allyl, N-propynyl, N,N-di-methyl, and compounds where the substituents with the nitrogen forms a pyrrolidine ring. The N-phenyl de­rivative, however, is much less ef­fective.

Indene analog is potential drug

U(IV) reduces cleanly in molten fluorides

152 ACS NATIONAL MEETING ND Medicinal Chemistry

Dr. T. Y. Shen and his coworkers have synthesized 1 -p-chlorobenzy lideny 1-5-methoxy-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 indometha­cin. The trans isomer, however, is only one fifth as active.

For the synthesis of the indene isostere, 6-methoxy-2-methyl-l-inda-none was condensed with ethyl bromo-

acetate under Reformatsky conditions to give the hydroxy intermediate. This intermediate was readily de­hydrated by acid to ethyl 5-methoxy-2-methyl-3-indenyl acetate. The in-denyl acetate was condensed with p-chlorobenzaldehyde in the presence of base to give the 1-p-chloroben-zylidene derivative. Of the two geo­metrical 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.

152 ACS NATIONAL MEETING ND Analytical Chemistry

Reduction of uranium (IV) at a plati­num electrode is a reversible, one-electron process in a mixture of lithium, beryllium, and zirconium fluorides at 500° C. This conclusion is based on a study of the electro­chemical 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 tempera­tures between 480° and 620° C. They obtained well-defined and re­producible voltammograms and chro-nopotentiograms at uranium tetra­fluoride 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 sci­entists say.

Dr. Mamantov and Mr. Manning ran a series of linear-sweep voltam­mograms 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 indi­cates that the redox reaction is a simple charge-transfer reaction. The results also show that at scan rates faster than 2 volts per minute dif­fusion is the predominant mass-trans­fer process.

Diffusion coefficients. From the linear-sweep voltammograms, the ORNL workers calculated the diffusion coefficient of uranium (IV), 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 co­efficient against the reciprocal of tem­perature, they obtained 10.5 kcal. per mole as the activation energy for dif­fusion 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 voltam-metric results also indicate that dis-proportionation of uranium (III) at 500° C. does not take place to an appreciable extent under the condi­tions of the experiment.

Nitrate ion oxidizes cycloheptatriene

152 ACS NATIONAL MEETING ND Organic Chemistry

When cycloheptatriene is oxidized by eerie ammonium nitrate, evidence points to the nitrate ion (free or com-plexed) as being the oxidizing agent. The finding suggests that other oxida­tions involving metal ions are possibly anion oxidations, the metal ions re-oxidizing the reduced anions, says Iowa State University's Dr. Walter S. Trahanovsky.

Cycloheptatriene's oxidation prod­ucts 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 an­hydrous 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 oxida­tion 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 am­monium nitrate oxidation is carried out in a variety of solvents of dif­ferent basicity, the ratio of benzalde­hyde to benzene end products changes only slightly. For example, in 50 r/c aqueous acetic acid, the ratio is 78 to 22. In anhydrous acetoni­trile, the ratio is 76 to 24. Dr. Tra­hanovsky argues that the insensi-tivity of the benzaldehyde-to-benzene ratio to solvent basicity suggests that a coordinated nitrate ion acts as a base during formation of benzalde­hyde.

Cyclic transition states involving ligands of a metal ion have been pro­posed for other oxidation reactions such as the oxidation of alcohols to ketones by chromium (VI) , Dr. Trahanovsky points out. However, experimental support for such transi­tion 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. Traha­novsky puts forward a somewhat complicated scheme to show how eerie ammonium nitrate oxidizes cy-

62 C&EN SEPT. 19r 1966

cloheptatriene. The first step in the oxidation sequence probably involves formation of a tropylium ion complex with the cerium. In support of this he cites the fact that the benzalde-hyde-to-benzene ratio varies only slightly when cycloheptatriene, tropyl­ium fluoroborate, tropylium bromide, and 7-ethoxycycloheptatriene are oxi­dized in 50% aqueous acetic acid.

In the next step, tropylium ion complex would then be converted to tropyl nitrate (free or complexed). The resulting heptatriene ring would rearrange to form a norcaradiene derivative which in turn would break down in two ways. In one, a neigh­boring nitrate ion would remove a proton from the cyclopropane ring to yield benzaldehyde. In the other, a shift of electrons would occur, caus­ing collapse of the cyclopropane ring and the formation of benzene and protonated carbon monoxide.

RESEARCH IN BRIEF

A five-membered-ring fluoronium ion seems to play a part in the 1,4-fluorine shift observed in the reac­tion of 5-fluoro-l-pentyne with tri-fluoroacetic acid. If so, it is the first recognized example of a reaction pro­ceeding via a cyclic fluoronium ion intermediate or transition state, note Dr. Paul E. Peterson and Ronald J. Bopp of St. Louis University (Mo.). The formation of 2-fluoro-2,5-ditri-fluoroacetoxy pentane when 5-fluoro-l-pentyne reacts with trifluoroacetic acid is indicative of cyclic fluoronium ion participation based on reaction ki­netics data. The ditrifluoroacetoxy derivative is likely the result of a very rapid interaction between 2-fluoro-5-trifluoroacetoxy-1-pentene ( formed initially) with a second molecule of trifluoroacetic acid, Dr. Peterson con­tends.

α Amino acids can be distinguished from their β- and γ-isomers on the basis of protonmagnetic résonance (PMR) data. Key to the technique is the upfield shift of the amino acids' methyl ester protons on tritylation of the amino groups. Dr. Charles H. Stammer and Ronald G. Webb of the University of Georgia, Athens, find that in the case of N-tritylated a-amino acid methyl esters, the carbo-methoxyl protons diamagnetically shift between 0.25 and 0.97 p.p.m. depending on the amino acid. The range of the upfield shift of carbo-methoxyl protons β and γ to the N-tritylated amino group is only 0.02 to 0.10 p.p.m. The proton diamag-netic shift is truly diagnostic for α-amino acids, Dr. Stammer points out.

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