RESEARCH
Biphenyls Used In Conformational Analysis Compounds used to study dissymmetric
New Conformational Concepts Developed for Studying: 1. Dissymmetric chromophores
chromophores, isotope effects, and angle strain Optically active biphenyls can be used in conformational analysis to develop concepts which can't be easily studied in more conventional alicyclic systems, Dr. Kurt M. Mislow of New York University, New York City, told the 18th National Organic Chemistry Symposium in Columbus, Ohio. Dr. Mislow has used the approach in studies of dissymmetric chromophores, steric isotope effects, and angle strain in conformational analysis (C&EN, June 24, page 4 1 ) .
The biphenyl system (left) contains many of the twisted ^--systems (skewed biphenyl itself, skewed nitrobenzene, and a skewed 0, 7-unsaturated ketone), which lead to high optical rotatory power. The alkylaryl sulfoxide (right) is another example of this type of system
2. Steric isotope effects
The deuterated compound on the left racemizes slightly faster than does its protium analog on the right. This effect must be steric in origin, Dr. Mislow says
3. Angle strain
Dissymmetric Chromophores. The biphenyl system differs from conventional alicyclic systems in an important way. Biphenyls are optically active without having an asymmetric carbon atom. They owe most of their optical rotatory power to a twisted 7r-electron system. These compounds correspond to what Dr. Albert Moscowitz of the University of Minnesota (Minneapolis) has called an inherently dissymmetric chromophore. Biphenyls occupy a unique position because the absolute configurations of many compounds in this class have been clearly worked out and defined, Dr. Mislow says. This has made possible a correlation between absolute sense of twist and the optical rotatory power (optical rotatory dispersion as well as circular dichroism). In collaboration with Dr. Carl Djerassi of Stanford University and Dr. Moscowitz, Dr. Mislow has shown that the sign and magnitude of the Cotton effect of inherently dissymmetric chromophores is related to the absolute chirality (handedness) of the twisted 7T system. This concept has been extended to systems other than 44
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Dithiepin Thiepin dibromide The optically active thiepin dibromide disproportionates spontaneously on standing at room temperature. But the racemic thiepin dibromide crystallizes and disproportionates only above its melting point of 150° C. Tetrabromide
the biphenyls. It has proved very useful in studies of such compounds as a,/3and /3,y-unsaturated ketones, and 1,3- and 1,4-dienes, he told the symposium. Dr. Mislow has also shown that in alkylaryl sulfoxides, the local phenyl and sulfoxide excitations couple to produce a dissymmetric -K system which leads to a high intensity Cotton effect. The approach developed for the biphenyls has proved valuable in judging the relative configurations and
conformation of compounds in the sulfoxide series. In addition, Dr. Mislow has shown that optically active alkylaryl and diaryl sulfoxides can be readily racemized under acid conditions in aqueous dioxane, and that the rates of racemization seem to depend on the size of the groups attached to the arylsulfinyl residues. Steric Isotope Effects. Restricted rotation around a single pivot bond depends on the size of the blocking
groups. Dr. Mislow has used this concept in an attempt to resolve ambiguity in the interpretation of some deuterium isotope effects. Specifically, he has prepared optically active 9,10-dihydro-4,5-dimethylphenanthrene and has compared its rate of racemization with the racemization rate of the corresponding compound deuterated in blocking or bridge positions. He finds that the compound deuterated in the blocking position racemizes faster (by about 13%) than does the nondeuterated compound. This is considered to be an example of a conformational kinetic isotope effect. The isotope effect is associated with a simple conformational change. This means that the difference in the racemization rates is caused by the difference in effective steric needs between CH 3 and CD 3 . The C D 3 has the lesser steric needs. But considering the tremendous compressions, Dr. Mislow believes that though this effect is real, it is surprisingly small. If this result is extrapolated to more complex systems in which bonds are made and broken, it strongly suggests that in some studies (by other workers), steric isotope effects could not have played a major role. Angle Strain. Dr. Mislow has prepared a series of double-bridged biphenyls in optically active form. These are the only compounds which are optically active and which have D2 symmetry. Their conformational stability is due mainly to a resistance to angle bending when the molecule is deformed. The NYU chemist contends that a study of unusual structural arrays is likely to produce unusual stereochemistry. An example is the synthesis of the double-bridged biphenyl "dithiepin," which can be made by a bimolecular disproportionation reaction. Racemic thiepin dibromide (as isolated from thiepin diol and phosphorus tribromide) crystallizes and disproportionates only above the melting point—150° C—to give an equimolecular mixture of dithiepin and tetrabromide. The optically active thiepin dibromide doesn't crystallize, thus can disproportionate spontaneously while standing at room temperature, accompanied by a mutarotation process. The effective results are that optically active and -racemic precursor thiepin diols give different products with PBr 3 . Optically active and racemic thiepin dibromides retain their integrity in solution.
Flocculation Theory Tested on Silica Filtration theory of flocculated suspensions upheld in silica suspension experiments Flocculation behavior of materials other than phosphates can now be predicted through the theory of filtration of flocculated suspensions. The theory was initially proposed in 1958 by Dr. R. H. Smellie, Jr., and Dr. Victor K. La Mer of Columbia University, New York City, working under an Atomic Energy Commission contract. The original theory (extended in 1962 by Dr. La Mer and Dr. T. W. Healy) was proposed for any solid material but tested only on phosphates. Now, new research at Columbia's chemical engineering department shows that the theory also holds for silica suspensions and ultimately could apply to many other solid suspensions. This means that it's possible to project mathematically the extent of flocculation needed to increase or decrease filtration to separate various materials. Such prospects could be significant to many industrial processes and particularly to water treatment. Proof that silica suspensions follow the theory of filtration has been ob-
tained, Jacqueline C. Kane, Dr. La Mer, and Dr. Henry B. Linford told the 37th National Colloid Symposium, held at Carleton University, Ottawa, Ont. The symposium was sponsored by the ACS Division of Colloid and Surface Chemistry. Miss Kane explains that the theory has been tested on several substances, including Florida phosphate, Colorado carbonate (uraniumbearing slimes), tricalcium phosphate, and now silica. She adds that there are many synthetic polymers which can flocculate solids from dispersions to improve settling and filtration rates. There is an optimum concentration of flocculant which produces the maximum settling and filtration. Therefore, filtration rate determinations are a rapid way to evaluate a polymer's flocculating ability. This can be summed up as an eighth power relationship between In ( P 0 V Q - Q 0 ) and In (P 0 + P m ) , where P 0 is added polymer, and Q and Q 0 are refiltration rates with and without added polymer.
EACH POLYMER HAS OPTIMUM CONCENTRATION
Solid content (grams silica/100 grams water) Optimum polymer concentrations are expressed here as grams/10 8 grams of water vs. solid content. The four polymers are the ones that effectively improve the refiltration rate with silica, the Columbia workers find JULY
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Settling rate measurements of the flocculated materials show a rapid aggregation period followed by subsidence, with packing occurring at increased time intervals. Many polymers show optimums in settling rates and final sediment volume measurements. Four effectively improve the refiltration rate with silica: two polyacrylamides, a polyethyleneimine, and a cationic guar gum. With the exception of the polyacrylamides, the polymers most successful in flocculating clay dispersions act as stabilizing agents in the silica suspension. While both silica and nonsilica substances display an optimum polymer concentration, magnitude and percentage of filtration improvement differ drastically. The optimum polymer concentration for nonsilica suspensions ranges from 30 to 1500 p.p.m.; for silica, from 0.3 to 10 p.p.m. Refiltration improvements for nonsilica suspensions range from 800 to 7000%; 330% is the maximum silica. These differences in behavior may be caused in part by the spherical nature of the silica particles, compared to flat-plate structures of other materials. Silica would form a more porous packing than would a flat particle, decreasing prospects for refikration improvement. However, the exact chemical interactions which cause these differences aren't known. But the agreement between theory and practice is remarkable, considering the difference in physical nature of the two materials, the Columbia scientists (whose latest work has been under a Public Health Service contract) p r m t out. They feel that the eighth wer relationship between polym id silica is established ber ycr>' ^e doubt by plotting results ration rate experiments in terms e eighth power equati n. The s; of the line is generally within ."'.•'; of 8 (the theoretical value) The relationship for silica between the amount of polymer giving maximvn flocculation and the solid content 1 definitely linear, Dr. La Mer, seni research investigator in mineral e^Sneering, and his co-workers say. With the phosphates, the relation ship is a linear dependence between the optimum polymer and the square of the solid content. Qualitatively, this can be exlained by assuming (depending on the system) that either a linear term or square term will dominate the above relationship. 46
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Condensation Leads to Glutamic Acid Lack of Krebs cycle in A. suboxydans explained by delineation of two new reaction routes Two new routes to the synthesis of glutamic acid in Acetobacter suboxydans have been found by a team of biochemists at Oregon State University, Corvallis. The findings could resolve a long standing mystery about the common, vinegar-forming bacteria. Most organisms form di- and tricarboxylic acids by means of a Krebs citric acid cycle, the Oregon State scientists told the 18th Annual Northwest Regional Meeting of the American Chemical Society, held at Western Washington State College, Bellingham, Wash. These then lead to synthesis of glutamic, aspartic, citric, and other organic acids. Eventually the systems yield carbon dioxide, water, energy,
amino acids, and cellular materials. However, nobody has yet turned up evidence of a Krebs cycle in A. suboxydans. Now Dr. Y. Sekizawa, Michael E. Maragoudakis, Dr. Annette Baich, Dr. Tsoo E. King, and Dr. Vernon H. Cheldelin have capped several years' study of A. suboxydans by finding two reactions that begin with condensation of simple molecules and end with glutamic acid. One of these reactions condenses glyoxylic acid with oxaloacetic acid, forming a hydroxy tricarboxylic acid similar to citric. The Oregon State group hasn't been able to identify the product completely, but it is a shortlived compound and difficult to ob-
One Route Condenses Glyoxylic with Oxaloacetic Acid, the Other Involves
Glyoxylic acid + oxaloacetic acid
Oxalomalic acid
7-Hydroxy-a-ketoglutaric acid
Oxaloacrylic acid
a-Ketoglutaric acid
