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| Experiment 8 | Synthesis and Purification of Diastereomers: Sodium Borohydride Reduction of a Chiral Ketone |
Notes
The positions of 1-3 on the TLC plate cannot be established using a UV lamp because these compounds do not absorb the lamp's UV radiation. You will visualize the plates using a chemical detection method, that is, you will treat your plate with a reagent that converts 1-3 into colored substances. The necessary reagent (a mixture of 2.5% 4-anisaldehyde, 1% acetic acid, and 3.5% sulfuric acid in 95% ethanol) will be provided to you and its use will be demonstrated in class. HAZARD: the reagent is highly corrosive and should only be used on a suitable surface and in a fume hood.
Use extraction-grade ether from the red cans.
The products are somewhat volatile, and removing ether with a rotary evaporator may result in an unacceptable loss of product. Simple distillation was covered last semester in experiment #2. Review that part of the manual for information about distillation principles and the set-up of your distillation apparatus.
The vapor from the boiling liquid will not make the apparatus hot enough for a successful distillation and will mostly condense in the flask. Once boiling begins, use a heat gun (HAZARD: heat guns become extremely hot; do not heat flammable material or material that might melt) to heat all of the upper flask and the distillation head.
Print out the full NMR spectrum, and expand the region from 3.5-4.5 ppm. Use "peak picking" to record the frequencies, not the chemical shifts, of each peak in the expanded region. Integrate the expanded region to find the cis/trans ratio. (Procedures for printing NMR spectra, expanding selected regions, peak picking, and integrating are posted online.)
Select Rings: Cyclohexane to introduce the ring.
Free rotation can occur around the CO single bond. This means each "chair alcohol conformer" is really a family of conformers that 1) share the same chair conformation, while 2) possessing different and unique OH orientations. You are interested only in the most stable member of each family. That is, you will take the strain energy of 2a to be the strain energy of the OH conformer of 2a that places the OH group in its most stable orientation. You will do the same for 2e, 3a, and 3e. (This is exactly analogous to the way you treated the ethyl group in 1-ethyl-3-methylcyclohexane in the molecular modeling activity.)
The best OH orientation must be identified by trial-and-error. You can, if you want, 1) build the same chair conformer with three different OH orientations (three is the magic number because there are three different ways to stagger the OH relative to the ring), 2) minimize the strain energy of each model, and 3) identify the OH orientation that creates the lowest strain energy and record its energy. The other, less stable, family members should be ignored.
Building hint #1: Rather than build three separate models with different OH orientations, just build a single model, minimize its energy and note the OH bond orientation. Then use internal rotation to re-orient the OH bond to a different staggered conformation, and minimize the energy again. Repeat for the third OH orientation. Remember, you are interested only in the OH orientation that gives the lowest strain energy.
Building hint #2: To change the orientation of the OH group by internal rotation, click on Add Fragment ("+") button so that the model-building tools are visible. Then click on the CO bond to make it active (a red arrow encircles the active bond). Simultaneously press the ALT key and LEFT mouse button and move the mouse to reorient the OH group.
