Lecture Outline Cyclohexanes with Two or More Substituents

Name ______________________________________ Today we'll be focusing on cycloalkanes with two or more substituents. Section 6.8 of the text covers these. Let's start by turning to p 209. That blurb in the margin looks like a useful hint or something that really should be memorized — ignore it. You'll spend way more time and effort trying to learn and apply that procedure than you will with the more general and reliable approach we'll learn in class. Until then you're better off building a model, puckering it into one chair, flipping it to the other, and looking at where everything ends up. The method used in the text to estimate the free energy difference between two chair conformers of a substituted cyclohexane is essentially the same approach that we used in the modeling lab — add up all the steric strains and compare. 1 Let's use this approach to predict the difference in energies between the two chair conformers of the following piperidine. N (CH3)2CH CH3 N (a) Start by attaching the isopropyl to the second chair. Caution: Be sure you get its bond to the ring in the correct position — look at a model. Also be sure that you write that isopropyl group in a valid way — it has a particular structure, it's not a random cluster of Cs and Hs. You can leave it in condensed form, just pay attention to which C is bonded to the ring! (b) Now attach the methyl to the N. But wait! Not so fast... Remember what we learned about NH3 — it's pyramidal (sp3), just like the N in the piperidine ring, but it inverts very easily via the trigonal planar (sp2) form. Of course this N can do the same thing, and inversion of the N is much faster (via a 5 kcal/mol barrier) than the chair-to-chair ring flip (via an 11 kcal/mol barrier). Now think about what this implies about the position of the methyl before you add it to the structure. (Unfortunately you don't have any "invertable" atoms in your model kit.) (c) Use the data from the table in the previous set of notes (or table 6.2 of the text) to estimate the total steric strain in each chair. (d) Based on your answer to part c, what is ΔG° for the ring flip as written above? Lecture outline Cyclohexanes with two or more substituents — Look at "up-down" relationships to go from flat drawing to chair and vice versa. Once you get the hang of this — by working with models, perhaps? — it's much easier than using mnemonics, memorizing rules about alternating "a"s and "e"s, brewing potions and chanting, etc. Let's go through this in excruciating detail just once... 1-bromo-2-methylcyclohexane CH3 H H Br cis first, take the "flat" structure and lay it down sideways — where are the methyl and bromo substituents and the Hs on those two Cs? Now grab the Cs at the extreme right and left of that structure and move one up and the other down to make the two chair conformers. Pay attention to which of the two things attached to each C is "up" and which is "down" (eq and ax will take care of themselves) Now do the same thing for the trans stereoisomer. CH3 H H trans Br Which of the two chair conformers of trans is more stable? Which of the two chair conformers of cis is more stable? Use the data in the table of axial substituent steric strains (last set of lecture notes and text table 6.2) to determine the total steric strain from axial substituents in each chair conformer. Now, in some chairs the CH3 and Br are gauche. We know from our analysis of butane that the steric clash of two gauche methyls is destabilizing by 0.9 kcal/mol. But do we have any data that might tell us the amount of destabilization to expect from a methyl-bromine clash? Hmmm... If we can estimate that, let's add it in. Now what's the difference in energy between the two conformers of the trans? What about the cis? Be sure you understand the difference between stereoisomers — cis and trans — these are configurationally different compounds that don't interconvert (how could they?!) and conformers — the two chair conformations of each one — these interconvert easily by rotations around σ-bonds. Keeping in mind that nearly all the molecules of a particular stereoisomer will be in the lower energy chair conformation, which stereoisomer is more stable, and by how much? Now draw the two chair conformers of the amine below and estimate their free energy difference. CH2CH3 NH2 (CH3)2CH steric strains: More examples and extensions as time permits...