LECTURE #19 Tues., Nov.08, continue Ch.5.

Transcription

1 EM 221 section 01 LETURE #19 Tues., Nov.08, 2005 ASSIGNED READINGS: TDAY S LASS: NEXT LETURE: continue h.5 finish h.5 (1) Back to thinking about practical things, like isolating compounds in the lab. W AN WE SEPARATE ENANTIMERS? Bruice 5.14: Resolution of racemic mixtures SEPARATING enantiomers in a racemic mixture requires SPEIAL TRIKS Techniques normally used to separate constitutional isomers and diastereomers work because compounds have DIFFERENT physical properties use distillation, recrystallization, chromatography The separation of a mixture of enantiomers is called the resolution of a racemic mixture (2)

2 Special tricks? USE IRALITY! Pasteur resolved crystals of sodium ammonium tartrate (obtained via making wine) by manually separating left- and right-handed crystals using a microscope to distinguish them visually. Biological resolution involves feeding a racemic mixture to a biological system which only converts one enantiomer to another product leaving behind the other enantiomer unchanged. TER WAYS IN LAB: LEVER modify enantiomers so they stop being enantiomers (3) A common way to separate enantiomers: chemically convert them into compounds that are diastereomers diastereomers AVE different physical properties result: can now separate compounds Final step: convert purified compounds back into previous form resolved enantiomers! E.g., reaction of a chiral acid with a racemic base r reaction of a chiral base with a racemic acid These give a mixture of salts that are diastereomers TUS: different physical properties, e.g., solubility TUS: can be separated by recrystallization AND, IMPRTANT FEATURE: easily reversible chemistry! (4)

3 (5) 2 * * N 2 2 N (R)-(-)-amphetamine (S)-(+)-amphetamine Racemic mixture [α] D = 0 2 N 3 React in (R)(2R,3R) salt diastereomers More soluble (could not predict ) ** (2R,3R)-(+)-2,3- dihydroxybutanedioic acid optically pure (+)-tartaric acid = resolving agent 3 N (S)(2R,3R) salt Less soluble can separate via crystallization (S)(2R,3R) salt 3 N Filter off crystals of the less soluble of the two diastereomeric salts recrystallize to purify it! K K/ 2 treat with base to deprotonate the ammonium ion regenerate amine! K soluble in water (deprotonated form of the resolving agent) 2 N insoluble in water (the desired cmpd) (S)-(+)-amphetamine, [α] D = +40 (6)

4 5.15 Discrimination of enantiomers by biological molecules Many naturally occurring compounds exist as one of two possible enantiomers All natural amino acids have the same handedness they are levorotatory, (L) or (-) Biological systems can distinguish between one enantiomer and its mirror image. Mirror images can behave quite differently under biological conditions (7) Why do the two enantiomers of chiral compounds interact differently with the body? All amino acids (except one) are chiral, so the enzymes they make are chiral as well The interaction between SUBSTRATE & ENZYME is superficially analogous to AND & GLVE ne enantiomer fits ther enantiomer DES NT (8)

5 Interactions between enzyme & substrate are stereospecific : only one stereoisomer works! orrect enantiomer interacts in all necessary places Incorrect enantiomer does not But it might interact with other important biomolecules!!! See more in 5.20 (9) 5.12: Rxns of cmpds with asymmetric carbons Does the configuration at asymmetric centres change? depends on whether or not bonds to asymmetric atom are broken during the reaction 1.) If no bonds to * broken: relative configuration same i.e., no change in relative positions of groups BUT: might have changed one of the substituents enough that priority of group changes! i.e., absolute configuration might change l - 2 Same relative & absolute configurations (10) = 2 2 Pd / 3 Same relative & but inverted absolute configuration

6 Does the configuration at asymmetric centres change? depends on whether or not bonds to asymmetric atom are broken during the reaction 1.) If no bonds to * broken: relative configuration unchanged 2.) If a bond to * is broken: configuration MAY change depends on mechanism of reaction! 3 Y Z z z + Y - Same relative pposite relative configuration configuration as reactant to reactant oming soon: mechanisms of this type of reaction! (11) 5.19 Stereochemistry of hydrohalogenation IF ALKENE IS ASYMMETRI, RXN AN YIELD 2 STEREENTRES: + can bond to either side of alkene 1 st is racemized nucleophile can attack planar carbocation from either side adjacent also racemized! TUS: yields 4 diastereomers! l + l 3 Descriptive terms: If it looks like both groups added to the same side of =: syn addition If added to opposite sides of =: anti addition (12) 3 l 3 l syn addition l 3 3 l anti addition

7 ASSIGNED READINGS BEFRE NEXT LETURE: Read: Practice: rest of h.5 predicting stereochemistry of products of alkene reactions (13)