Chapter 07 Stereochemistry

Transcription

1 Chapter 07 Stereochemistry CHEM 341: Spring 2012 Prof. Greg Cook

2 STERECHEMISTRY CHIRALITY A C A C B C D D C B

3 Symmetric Molecules 3

4 Chirality - Stereoisomers 4

5 Chirality - Stereoisomers 4

6 Chirality Enantiomers - molecules that are not superimposable on their mirror image. Molecules that can exist as enantiomers are called Chiral Molecules. Molecules that have a plane of symmetry are not chiral (achiral). Stereogenic Carbons are those that have four different groups attached. 5

7 Symmetry - Assymmetry 6

8 Biomolecules are Chiral H H Carbohydrates / Sugars H H H H H H H Glucose H DNA Amino Acids / Proteins H 2 N H R 7

9 Chirality in Smell and Taste Mirror image molecules (enantiomers) interact with chiral receptors in our nose differently. (R)-(-)-Carvone spearmint oil (S)-(+)-Carvone caraway seed oil (R)-(+)-Limonene orange citrus (S)-(-)-Limonene turpentine/lemon 8

10 Chiral Molecules in Enzymes N Me H H NH N H 9

11 The Case of Thalidomide N stereogenic carbon N (R)-thalidomide beneficial sedative * N H N H * (S)-thalidomide teratogen causes birth defects 10

12 ptical Activity Enantiomers have identical physical properties mp, bp, spectroscopic, absorptions, etc. BUT they are different when interacting with plane-polarized light Christiaan Huygens - ( ) Dutch astronomer, mathematician, and physicist, discovers plane polarized light 11

13 ptical Activity Jean-Baptiste Biot ( ) In 1815 he discovers that certain natural organic compounds rotate plane polarized light. light travels in waves but oscillates in all three dimensions along the path of travel Light is polarized and oscillates in a single dimension chiral sample when the polarized light passes through a chiral sample, it is bent out of the original plane chiral sample enantiomer Note that the enantiomer will bend the light in the opposite direction polarizing filter 12

14 Tartaric Acid Hi Carl Wilhelm Scheele ( ) In 1769 he discovers Tartaric Acid from tarter - the potassium salt of tartaric acid that crystallizes out of wine. In 1769, he disc Acid from tarta salt of tartaric on barrels and H fermentation o H * * H H 13

15 Tartaric Acid Louis Pasteur - ( ) In1849 he separated mirror image crystals of sodium ammonium tartrate. Na NH 4 H * * H 14

16 Louis Pasteur I found...that the tartrate was hemihedral..., but strange to say the paratartrate was hemihedral also. nly the hemihedral faces which in the tartrate were all turned the same way, were, in the paratartrates inclined sometimes to the right and sometimes to the left... I carefully separated the crystals that were hemihedral to the right from those hemihedral to the left, and examined their solutions separately in the polarizing apparatus. I then saw with no less surprise than pleasure that the crystals hemihedral to the right deviated the plane of polarization to the right, and that those hemihedral to the left deviated it to the left; and when I took an equal weight of each of the two kinds of crystals, the mixed solution was indifferent towards the light in consequence of the neutralization of the two equal and opposite individual deviations. 15

17 ptical Activity Amount of rotation depends on how many molecules the light interacts with. Light at 589 nm (Sodium D line) Standardized for unit cell and concentration [α]d = observed rotation ( ) cell length (dm) x conc. (g/ml) 16

18 Racemates...when I took an equal weight of each of the two kinds of crystals, the mixed solution was indifferent towards the light in consequence of the neutralization of the two equal and opposite individual deviations. Racemic Mixture - 50/50 mixture of enantiomers. Shows N optical activity. light travels in waves but oscillates in all three dimensions along the path of travel Light is polarized and oscillates in a single dimension when the polarized light passes through a chiral sample, it is bent out of the original plane Note that the enantiomer will bend the light in the opposite direction chiral sample chiral sample enantiomer polarizing filter 17

19 Asymmetric Carbon Joseph A. Le Bel - ( ) Jacobus H. van t Hoff - ( ) In 1874 they proposed that carbon with four ve attachments is tetrahedral and that Joseph A. molecules with four different attachments may exist as a pair of isomer. Jacobus H. 18

20 Good Ideas are Criticized Hermann Kolbe - ( ) In 1877 he published a harsh criticism of van t Hoff s work I have recently published an article in Journal für praktische Chemie (14, 288 ff.) giving as one of the reasons for the contemporary decline of chemical research in Germany the lack of well-rounded as well as thorough chemical education. Many of our chemistry professors labor with this problem to the great disadvantage of our science. As a consequence of this, there is an overgrowth of the weed of the seemingly learned and ingenious but in reality trivial and stupefying natural philosophy. This natural philosophy, which had been put aside by exact science, is at present being dragged out by pseudoscientists from the junk-room which harbors such failings of the human mind, and is dressed up in modern fashion and rouged freshly like a whore whom one tries to smuggle into good society where she does not belong. Whoever considers this apprehension to be exaggerated should read, if he can manage it, the recently published pamphlet, "The arrangement of atoms in space", by Messrs. van't Hoff and Herrmann, which teems with fantastic trifles. I would ignore this paper as so many others if it were not for a renowned chemist who protected this nonsense and recommended it warmly as meritorious accomplishment. 19

21 Good Ideas are Criticized A J. H. van't Hoff who is employed at the Veterinary School in Utrecht appears to find exact chemical research not to his taste. He deems it more convenient to mount Pegasus (evidently loaned from the Veterinary School) and to proclaim in his "La chimie dans l'espace" how, to him on the chemical Parnassus which he ascended in his daring flight, the atoms appeared to be arranged in the Universe. It is completely impossible to criticize this booklet in any detail because the fancy trifles in it are totally devoid of any factual reality and are completely incomprehensible to any clear-minded researcher. But in order to get some idea what notions the authors might have had, it suffices to read the following two sentences. The brochure begins with the words: "The modern chemical theory has two weak points. It says nothing either about the relative position or the motion of the atoms within the molecule." The other sentence, on top of page 35 of the brochure, reads: "In the asymmetrical carbon atom we have a medium which is characterized by the screwlike arrangement (sic!) of its smallest particles, the atoms!?" In order to avoid the reproach that it is not permitted to quote sentences out of context, I refer to the pamphlet itself. Everyone will convince himself that these sentences read in context are just as baroque and incomprehensible as by themselves. It is characteristic of today's uncritical and criticism-hating time, that two virtually unknown chemists, the one from a veterinary school, the other from an agricultural institute, judge the most profound problems of chemistry which probably will never be answered. They judge these most important problems, especially the question as to the spatial orientation of the atoms, with a cock-sureness and insolence which can only astound a true student of natural science. van t Hoff received the first nobel prize in Chemistry in

22 CIP Rules for R & S Configuration Rectus - Right, Sinister - Left 1 Cl H 4 4 H Cl (S)-2-chlorobutane 3 2 (R)-2-chlorobutane 21

23 R & S Configuration NH 2 H H sphingosine H NH 2 R H 22

24 R & S Configuration H 2 N H CH 3 alanine H N H proline 23

25 R & S Configuration H H H S S R R S H glucose H 24

26 Axial Chirality H H Cl H 3 CH 2 C H H H 3 CH 2 C CH 3 enantiomers Cl CH 3 H H enantiomers H H 25

27 Reactions can produce stereogenic centers Racemic mixtures will always result unless there is other chirality to influence a difference in the reaction path. H R S + 50:50 26

28 Diastereomers Diastereomers - stereoisomers that are not mirror images 27

29 Diastereomers Diastereomers - stereoisomers that are not mirror images STEREISMERS DIASTEREMERS ENANTIMERS 27

30 cis/trans Diastereomers Although not optically active (not chiral), cis/trans isomers are a form of diastereomer. They differ only in their arrangement in 3-dimensions but are not mirror images. 28

31 configurational Diastereomers ENANTIMERS H H S R H H H H S H S R H H H DIASTEREMERS H R H DIASTEREMERS 29

32 MES compounds Meso Compounds are molecules that contain stereogenic carbons, but are not chiral. Their mirror images are identical. This occurs when there is a plane of symmetry in the molecule. H H H H S R R S H H H H IDENTICAL 30

33 Diasteromers Diastereomers have different physical properties molecule H H H H H H H H H H H H config optical rotation (S,S) +12 (R,R) -12 (S,R) meso 0 mp C C C density

34 ISMERS ISMERS (same number and kind of atoms, but are different molecules) Constitutional (bonded differently) Stereoisomers (nly different in 3-dimensional arrangement) Enantiomers (mirror images) Diastereomers (not mirror images) Configurational cis/trans 32

35 Reactions can produce stereogenic centers Racemic mixtures will always result unless there is other chirality to influence a difference in the reaction path. H R S + 50:50 33

36 Chirality in Reactions

37 Chirality in Reactions 2 S S R R + enantiomers cis-2-butene S S R R 35

38 Chirality in Reactions 2 + identical trans-2-butene MES 36

39 Diastereoselectivity An existing stereogenic center can influence the creation of another. H 3 C 2 H 3 C Major Product H 3 C Major Product H 3 C H 3 C 37

40 Resolution of Enantiomers The separation of enantiomers from a racemic mixture is called a resolution. Na NH 4 H * * H 38

41 Fischer Projections 39

42 Chemical Resolution Enantiomers have identical physical properties, so we need to prepare diastereomers. H R H S racemic mixture H H + NH 2 S one enantiomer H R H S + diastereomeric salts NH 3 S NH 3 S 40

43 Chemical Resolution We can also make covalent bonds. NH 2 HN S S S Ph Racemic Mixture NH 2 R + Cl S one enantiomer HN R Ph diastereomeric products S 41

44 Indication of mixed stereochemistry NH 2 Racemic Mixture 42

45 Chirality on other atoms Nitrogen would be chiral if it did not invert rapidly at room temperature B N C A enantiomers A C N B B N C A 43

46 Chirality on other atoms Phosphorous is difficult to isomerize and does not invert at room temperature. B P C A enantiomers A C P B B P C A 44