The Baeyer Laboratory, Munich, 1893 (This photograph is in the hallway across from 110 SCL) Adolf von Baeyer (1835-1917); Nobel Prize 1905. (center, seated with derby), who was a student of Kekulé, succeeded Liebig at Munich. In the photograph (second row; third from right) is Henry Lord Wheeler (1867-1914); Yale Faculty 1896-1911. As was the custom in the 19th century, many Americans, such as Wheeler, did advanced study in chemistry in Europe. Karl is the laboratory assistant. (The only person wearing an apron and no tie; upper left.) In 1885, as an addendum to a paper on acetylenic compounds, Baeyer proposed that cyclopentane was the least strained of the cycloalkanes . While he accepted the idea that the carbon atoms in cycloalkanes were tetrahedral, he treated the cycloalkanes as though they were flat. He argued that there is only one cyclohexane carboxylic acid, not two (axial and equatorial) as was predicted by a chair cyclohexane. Equatorial is frequently misspelled.

Sir Derek H. R. Barton (1918-1998) 1969 Nobel Prize with Odd Hassel for their work on conformational analysis For a video of Barton talking about conformational analysis, click here. Cyclohexane in the chair conformation (How to manipulate JSmol structures)

a. Work through How to Draw Cyclohexanes (PowerPoint)

b. The Conformation Module in the Study Aids will give you a good overview of the subject of conformation of cycloalkanes.

1. Compound A (MW=140.22), a 1,4-disubstituted cyclohexane, has the following composition: C, 77.09% and H, 11.50%. (What else is there?) The difference in conformational energy for the two chair conformations of A is 1.3 kcal/mol. Using the A-value data (Energy Differences Between ..... Cyclohexanes), determine the structure of A. Illustrate and explain. What is the conformational energy difference for the stereoisomer of A, ---namely A'. Explain and illustrate. Show the chair comformations of A and A' with the appropriate equilibrium arrows to illustrate the major and minor conformations. Label each conformation with its energy.

2. Unknown compound (R)-(+)-A (C₁₀H₁₆; [α]_d=124^o) reacts with two molar equivalents of hydrogen to produce two 1,4-disubstituted cyclohexanes, B and C, both of which are optically inactive. Compound B has an energy difference between its two chair conformations of 0.3 kcal/mol, while compound C's difference is 3.9 kcal/mol. Ozonolysis of A provides one mole of formaldehyde and one mole of an optically active diketoaldehyde D. What are the structures of A-D? Show your reasoning.

3. Draw the 3-D line-angle structures of the major products in each of the following reactions. Pay attention to stereochemistry, optical activity and racemic mixtures. Explain briefly.

4. In 1886, Albert Ladenburg, synthesized the Socratic poison, coniine [2-propylpiperidine (1)], in racemic form. He resolved the racemate into its enantiomers using the reverse of the technique employed by Pasteur ~25 years earlier. a) What did Ladenburg do? b) Was he able to predict which enantiomer he would isolate in his very first experiment? Elaborate. c) The enantiomer of coniine present in hemlock (Conium maculatum L., Umbelliferae ) is (S)-(-)-coniine, [α]D = -18o. Draw the (S)-enantiomer of coniine. d) Assume that Ladenburg obtained a sample of coniine on his first resolution that had [α]D = +16o. What should he have concluded about his resolving agent? How much of each enantiomer would have been in his sample?		Albert Ladenburg (1842 - 1911)

5. Using the Heats of Formation Table list the values for the cycloalkanes in column 2. Which of these cycloalkanes is the least strained? Place its heat of formation in column 3. Compute the hypothetical heats of formation for the remaining alkanes (Remember the magic number in kcal/mol!). Compute the difference in heats of formation of each cycloalkane (pay attention to + and - signs) in column 4 (column 2 minus column 3). What have you calculated in column 4? Find these data in the Thermochemistry Module and compare your answer. Good or bad correlation?

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