All these can be related to normal and abnormal behavior. So it is easy to see why this area of research is hot and, for the better investigators, thriving. The world "better" deserves emphasis, because LSD isn't available to everybody for research. Investigators must apply for samples to a joint FDA-NIH committee much as they would apply for a grant. BDAC's Dick Callahan, as scientifically sophisticated a gumshoe as ever wore an investigator's badge, and Dan Freedman, an investigator in a different dimension, are far apart in their operational perspective on LSD and other hallucinogens. Callahan knows these drugs can hurt p e o p l e directly and indirectly. He's seen it happen; hospital records bear him out. He sees drug use and abuse as symptomatic of a confused valueless family setting. He may be right. Other aspect. There is another aspect. LSD is real. Powerfully so. Only a small fraction of the 100-microgram trip dosage actually reaches the brain and exerts its profound effect. Under the best of conditions—mystical experiences aside—the trip can afford at least transitory benefits. There are those who support that claim. Some psychiatrists, Dr. Sidney Cohen, author of "The Beyond Within," for one, say it produces the type of insights that months and years of psychotherapy eventually raise to the surface. Dr. M. Robert Wilson of the Mayo Clinic says that students who only rarely use the drugs have returned to their academic surroundings better able to cope with the various pressures students feel today. Dr. Cohen declares that LSD does not seem to enhance creativity. Moreover, continued use lengthens a person's dependence on society. For the moment, the thoughts of Dr. Freedman may suffice. In his paper in the recently published book, "Ethnopharmacologic Search for Psychoactive Drugs: 1967" he says: "It seems to me that we have been more awed than aided by our experience with these drugs. They still remain agents which reveal but do not chart the mental regions; to do that we must employ our mental faculties available in the undrugged state . . . . "We should strive to make distinctions so that—at some future date—if we knew how the elements of mind really were related, we could specify for the chemist the designs he should seek in nature. But to begin with we have to learn to analyze how behavior is organized, and to see what nature can teach us about the ways in which the chemical organization of the brain is related to the dimensions of the mind." 38 C&EN MARCH 11, 1968
Tobacco's pyrolytic path involves several types of intermediates Tobacco's pyrolytic path to polynuclear aromatic hydrocarbons (allegedly biologically active) involves not only free radicals, but several types of chemical intermediates. Included are common pyrolysis intermediates, phenylcarbenes, and four-membered ring compounds, presumably dimerization products, according to Dr. Teresa C. Jones and Dr. Irwin Schmeltz of U.S. Department of Agriculture's Eastern Utilization Research and Development Division in Philadelphia, Pa. These conclusions are based on a detailed study of the pyrolysis of cinnamic acid and related tobacco leaf constituents. In addition to cinnamic acid, a number of compounds in tobacco contain the cinnamate group. Assuming that cinnamic acid is a phenylethylene analog, the USDA group pyrolyzed several other phenylethylenelike compounds such as sodium cinnamate, frans-stilbene, distyryl, and styrene. They chose pyrolytic conditions to emulate a burning cigarette at 850° C , Dr. Jones points out. Each compound exhibits analogous behavior on pyrolysis from 420° to 820° C. Moreover, frans-stilbene was formed as an intermediate when each of the other phenylethylenelike compounds was pyrolyzed. frans-Stilbene is structurally related to stilbestrol, a biologically active compound. Furthermore, yields of the condensable neutral fractions are relatively high—18 to 70%— for high-temperature pyrolysis in all cases. The product neutrals, analyzed by gas-liquid partition chromatography, are generally complex mixtures composed of at least 30 detectable compounds. Styrene, toluene, frans-stilbene, phenanthrene, and 1-phenylnaphtha-
lene are the major products from cinnamic acid and sodium cinnamate pyrolysis. In the precursor-to-product route, yields of benzene and biphenyl increase "dramatically" as the temperature rises from 420° to 820° C. This is due to greater phenyl radical production at higher temperatures, the USDA chemists explain. At the same time, yields of fused-ring aromatics, such as naphthalene, indene, acenaphthene, fluorene, fluoranthene, and pyrene, also increase as the temperature nears 820° C. The most common of the major pyrolysis products is frans-stilbene. It is found in high yields at relatively low temperatures (about 420° C ) , where there are few indications of free-radical fusion to form benzene or biphenyl. What might possibly occur, the USDA team postulates, is that a nonfree-radical mechanism exists which gives rise to trans-stilbene via a diphenylcyclobutanelike intermediate or via a phenylcarbene. Phenylcarbene as a precursor of trans-stilbene was reported in 1960 by Dr. H. E. Zimmerman and Dr. D. Somasekhara at Northwestern University, Evanston, 111. Dr. Zimmerman is now at the University of Wisconsin. The reasons the USDA chemists give in support of a cyclobutanelike intermediate include: • It is conceivable that such a transition state can lead to both styrene and stilbene. • Styrene dimerizes to 1,2-diphenylcyclobutane upon heating. • irans-Stilbene also dimerizes when heated. • Cinnamic acid dimerizes to truxillic and truxinic acid ( diphenylcyclobutane dicarboxylic acids) upon photolysis and pyrolysis.
OTHER STUDIES. Dr. T. C. Jones (foreground) and Dr. Irwin Schmeltz will study the pyrolytic pathways of substituted cinnamic acid, truxillic and truxinic acids, 1,1-diphenylethylene, and phenylnaphthalene. In addition, they plan isotope mixing experiments on the phenylcarbene intermediate reaction
