Presentation on theme: "Chemistry 125: Lecture 32 Stereotopicity and Baeyer Strain Theory"— Presentation transcript:
1Chemistry 125: Lecture 32 Stereotopicity and Baeyer Strain Theory Why ethane has a rotational barrier is still debatable. Analyzing conformational and configurational stereotopicity relationships among constitutionally equivalent groups reveals a subtle discrimination in enzyme reactions. When Baeyer suggested strain-induced reactivity due to distorting bond angles away from those in an ideal tetrahedron, he assumed that the cyclohexane ring is flat. He was soon corrected by clever young Hermann Sachse, but Sachse’s weakness in rhetoric led to a quarter-century of confusion.Synchronize when the speaker finishes saying “…and that you could measure the barrier.” Synchrony can be adjusted by using the pause(||) and run(>) controls.For copyright notice see final page of this file
2Is the Minimum eclipsed or staggered? 3 kcal/molEnergy0°120°240°360°Torsional Angle
4What is the source of the ~3 kcal/mole barrier in Ethane? (a) Eclipsed form destabilizedor(b) Staggered form stabilized?CHCH(Compared to what?)H-H repulsiononly 3.4 kcal/molefor propane(so "size" of H isnot very important)e-e repulsionBut there are alsop-e attractions.
5What is the source of the ~3 kcal/mole barrier in Ethane? (a) Eclipsed form destabilizedor(b) Staggered form stabilized?CH+_HOMO/LUMOmixingC=CH+H_"hyperconjugation"ss
6A Digression on Topicity (Placeness) Are these two protons equivalent?and their propertiesYes, but their environments are different.D+HCO:++HHpKa ~16Exchanges readily with acidic waterDoesn’t exchangepKa ~50These protons are “heterotopic” (Greek: ó, topos = place)Protons within the blue (or green) set are “homotopic”Here we are discussing constitution; the distinctions are less trivial and more useful when they are stereochemical.
7Stereotopic Relationships among atoms (or groups) that are constitutionally homotopicenantiotopicHCOHdiastereotopicenantiotopicThese distinctions are only conformational.They are erased by rotation within ~10-12 sec.This distinction is configurational and lasts as long as bonds endure.
8Toponymy OH H pro-S pro-R O H C H among atoms (or groups) that are constitutionally homotopicHCOH“prochiral” C(i.e. would be chiral, if the enantiotopic atoms differed)21HOHenantiotopicGive higher priority to enantiotopic H being named.3443pro-Spro-R
9Reactivity Difference? among atoms (or groups) that are constitutionally homotopicAttacks by a reagent like Cl• are mirror images and thus identical in rate.HOHCl••Clpro-Spro-R
10Reactivity Difference? among atoms (or groups) that are constitutionally homotopicAttacks by a resolved chiral reagent are diastereomeric and should have different rates.HOHRightRightpro-Spro-R
11Establishing Enzyme Specificity O-HDHODLAD+ NADH+ NAD+If horse liver alcohol dehydrogenase (LAD) removes only the pro-R H from ethanol, it should remove H (never D) from (S)-1-deuteroethanol.Westheimer [J. Am. Chem. Soc., 1951, 73, 2043; J. Biol. Chem., 1953, 202, 687]“Stereospecificity in Enzymology: Its Place in Evolution”,Topics in Stereochemistry, Volume 19 , Pages , 1989.Steven A. Benner (Chem 125 alumnus), Arthur Glasfeld, Joseph A. PiccirilliThese focus more on selectivity between the enantiotopic hydrogens of the cofactor NAD(P)H than on those of the substrate.Good test, but where to get the (S)-1-deuteroethanol?By starting with same catalyst, CH3CDO and excess NADH.A full cyclereturns CH3CDO with all of its initial D intact![This proves specificity. Whether pro-R or pro-S required more work.]Actually LAD is a catalyst for oxidation by “NAD+”.
12Baeyer Strain Theory (1885) Adolf von BaeyerAcademy of Science, Munich, 1893Seehttps://webspace.yale.edu/chem125/125/history99/6Stereochemistry/Baeyer/strainl
13On Polyacetylene Compounds (1885) They explode! (Dr. Homolka?)1. Theory of Ring Closure and the Double BondRing closure is apparently the only phenomenon that can supply information about the arrangement of atoms in space. Since a chain of 5 or 6 members can be closed easily, while with one of more or fewer members it is difficult or impossible, spatial factors are apparently involved.
14The previously proposed general rules on the nature of carbon atoms are the following: I. Carbon is as a rule tetravalent.II. The four valences are equivalent, as shown by the fact that there is only one monosubstitution product of methane.III. The four valences are equivalently arranged in space and corres-pond to the corners of a regular tetrahedron inscribed in a sphere.IV. The atoms or groups attached to the four valences cannot exchange places. Evidence: there are two tetrasubstitution products abcd of methane, LeBel-van't Hoff Rule.V. Carbon atoms can bind to one another with 1, 2, or 3 valences.VI. These compounds can form either open or closed-ring chains.
15I should like to add the following to these generally accepted rules: VII. The four valences of the carbon atom point in the directions connecting the center of the sphere to the corners of the tetrahedron, forming an angle of 109°28' with one another.The direction of attachment can undergo alteration, but a strain is generated increasing with the size of the deflection
16Dimethylene is indeed the weakest ring, which can be opened by hydrogen bromide, bromine and even iodine; trimethylene is broken only by hydrogen bromide but not by bromine; finally tetramethylene and hexamethylene are difficult or impossible to break.
19"It is not possible to write an abstract of this paper, especially since the author's explanations are hardly understandable without models."Julius Wagner (1890)
20Baeyer (1890)A further proposal is that the atoms in hexamethylene are arranged as in Kekulé's model, that is that the arrangement of the atoms in space is the one with a minimum distortion of the valence directions.Thus the 6 carbon atoms must lie in one plane and 6 hydrogen atoms lie in each of two equidistant parallel planes. Further each of the 12 hydrogen atoms must have the same position relative to the other 17 atoms.The experimental test of the correctness of this assumption isrelatively easy, for example sufficient evidence is that there is a single isomer of hexahydrobenzoic acid [i.e. only one cyclohexane carboxylic acid].Meanwhile, as long as our knowledge in this field is so incomplete, we must be satisfied that the above assumption is the most likely, and no known fact contradicts it.
21Sachse (1892) 41 pp. in Zeitschrift für Physikalische Chemie edited by Ostwald, who did not believe in atoms and wrote dispar-agingly of his successor in Riga,"Scientifically he had been brought up in the narrow circle of contemporary organic chemistry, and to him the arrangement in space of the atoms of organic compounds was the foremost of all conceivable problems."
22Sachse (1893) 34 pp. in Zeitschrift für Physikalische Chemie died at age 31 in 1893Baeyer (1905)"Sachse…disagreed with my opinion that larger rings are planar. He is certainly right from a mathematical point of view; yet in reality, strangely enough, my theory appears to be correct. The reason is not clear…"
23What important lesson should we all take from the tale of poor Sachse?