Chemistry 125 Lecture 26 van t Hoff s Tetrahedral Carbon

Chemistry 125: Lecture 26 van’t Hoff’s Tetrahedral Carbon and Chirality With his tetrahedral carbon models van’t Hoff explained the mysteries of known optical isomers possessing stereogenic centers and predicted the existence of chiral allenes, a class of molecules that would not be observed for another 61 years. Symmetry operations that involve inverting an odd number of coordinate axes interconvert mirrorimages. Like printed words, only a small fraction of molecules are achiral. Verbal and pictorial notation for stereochemistry are discussed. Synchronize when the speaker finishes saying “…from Kolbe on the young van’t Hoff. ” Synchrony can be adjusted by using the pause(||) and run(>) controls. For copyright notice see final page of this file

van't Hoff’s Optically Active Compounds Lactic Acid Tartaric (CH 3)CH(OH)(CO 2 H) Scheele Liebig Wislicenus right, left, and inactive Acid (CO 2 H)CH(OH)(CO 2 H) Encyclopaedia Britannica, 1911: Wislicenus) (Scheele, Berzelius, Pasteur, LACTIC ACID (hydroxypropionic acid), C 3 H 6 O 3. Two lactic acids are Aspartic Acid (CO 2 H)CH(NH 2). CH 2. (CO 2 H) known, differing from each other in the position occupied by the hydroxyl group in the molecule; they are known respectively as -hydroxypro. Amyl Alcohol (CH 3)(C 2 H 5)CH(CH 2 OH) pionic acid (fermentation, or inactive lactic acid), CH 3 CH(OH). CO 2 H, and 3 -hydroxypropionic acid (hydracrylic acid), CH 2(OH)CH 2 CO 2 H. Glucose COH(CHOH)4 CH 2(OH) (Levulose, Lactose) Although on structural grounds there should be only two hydroxypropionic acids, as a matter of fact four lactic acids are known. The third Malic Acid (CO 2 H)CH(OH). CH 2. (CO 2 H) isomer (sarcolactic acid) is found in meat extract (J. v. Liebig), and may be prepared by the action of Penicillium glaucum on a solution of ordinary HI/P OH H “reduction” & Most of their D It is identical with -hydroxypropionic acid in almost ammonium lactate. but not (Bremer & van't Hoff) Derivatives, every respect, except with regard to its physical properties. The fourth ! isomer, formed by the action of Bacillus laevo-lacti on cane-sugar, 2 H) (CO 2 H)CH 2(CO 2 H)HC=CH(CO 2 H) resembles sarcolactic acid in every respect, except in its action on Maleic & Fumaric Acids inactive Succinic Acid polarized light. “…the fancy trifles in it are totally devoid of any factual reality…” Constututional Kolbe on van’t Hoff (1877) Isomers

van't Hoff Obituary (1911) In his whole life he never made what would be called a very accurate measurement, and he never cared to. I remember his saying to me eighteen years ago, “How fortunate it is that there are people who will do that sort of work for us!”

van't Hoff’s Optically Active Compounds Lactic Acid (CH 3)CH(OH)(CO 2 H) Tartaric Acid (CO 2 H)CH(OH)(CO 2 H) Aspartic Acid (CO 2 H)CH(NH 2). CH 2. (CO 2 H) Amyl Alcohol (CH 3)(C 2 H 5)CH(CH 2 OH) Glucose (Levulose, Lactose) Malic Acid & Most of their Derivatives, but COH(CHOH)4 CH 2(OH) (CO 2 H)CH(OH). CH 2. (CO 2 H) D “reduction” (Bremer & van't Hoff) (CO 2 H)CH 2(CO 2 H)HC=CH(CO 2 H) Maleic & Fumaric Acids in solution Succinic Acid "Every carbon compound which inactive can rotate the plane of polarized light contains one or more asymmetric carbon atoms. "

van’t Hoff Cardboard Models (Bremer’s set, in Museum Boerhaave, Leiden) Ladenburg Benzenes Colored Vertices Colored Faces (from T. M. van der Spek, Annals of Science, 2006)

Maleic and Fumaric Acids

van’t Hoff made this diagram to show that free rotation about the central bond results in rapid interconversion (and thus inseparability and irrelevance) of “Paternó isomers. ” Note that R 1, R 2, R 3 (and R 4, R 5, R 6) can be arranged clockwise or counterclockwise about the C-C axis. This sequence is permanent and unaffected by C-C rotation. If R 1=R 4, R 2=R 5, R 3=R 6, as in tartaric acid, there are three possible isomers: cw-cw, ccw-ccw, and cw-ccw. If 123≠ 456, there is a fourth isomer ccw-cw. For mesotartaric acid, there is no net effect on polarized light, because the ccw half cancels the cw half. Free Rotation : Tartaric / meso

van’t Hoff predicts handedness 1874

61 years after van’t Hoff prediction of 1874 C 6 H 5 tetrahedral bonds C 10 H 7 6 H 5 must break coplanar C 10 H 7 6 H 5 C C C bonds? bond to C 6 H 57 isomerize to 10 H OCOCH 2 COOH C 6 H 57 mirror image 10 H

Isomer Numbers for “Dewar's” 3 D Benzene Structures "Prismane" or "Ladenburg Benzene" "Dewar Benzene" ? MONO 2(1) 3(3) 2(1) (additional number if mirror-images count for these nonplanar structures) 0 top 3(2) 0 mid 0 bottom 3(1) 0 total 6(3) DI (subtotals with total in Red) 5(4) 3(2) 1 9(6) 3(2) 3(1) 6(3) 5(3) 1 6(3) 3(1) assuming free rotation of CH 3 1 3(2) 2 5(2) 3(1)

on top Mirror Images Top is on right is Right It exchanges front and back, Q. Why intuition interprets as rotation which ourdoes a mirror exchange right. and vertical axis (exchanging right and about theleft, but not top and bottom? left), because Actually it changes neither. A. people pivot, but don’t "invert".

Right Arm Oxford Mathematician blind in one eye special. lib. gla. ac. uk/ exhibns/month/mar 2000. html

Right Arm Left special. lib. gla. ac. uk/ exhibns/month/mar 2000. html

"Now, if you'll only attend, Kitty, and not talk so much, I'll tell you all my ideas about Looking-glass House… “Well then, the books are something like our books, only the words go the wrong way; I know that, because I've held up one of our books to the glass, and then they hold up one in the other room… "How would you like to live in Looking-glass House, Kitty? I wonder if they'd give you milk, there? “Perhaps Looking-glass milk (sarcolactic? ) isn't good to drink. E. Heilbronner, J. D. Dunitz, Reflections on Symmetry, 1993, p. 86

Chirality (Greek “ eir” hand) “I call any geometrical figure, or group of points, chiral, and say that it has chirality, if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself. ” Lord Kelvin (1894)

Chirality (Greek “ eir” hand) Change Sign of all X Coordinates?

Reflection in yz Mirror Change Sign of all Y Coordinates?

Reflection in xz Mirror Change Sign of all Z Coordinates?

Reflection in xy Mirror Change Sign of all X & Y Coordinates?

Rotation about z Axis Change Sign of all X & Z Coordinates?

Rotation about y Axis Change Sign of all Y & Z Coordinates?

Rotation about x Axis Change Sign of all X&Y&Z Coordinates?

Inversion through Center of Symmetry

Chirality - Non-superimposable Mirror Images The right hand has only one mirror image, but different mirrors (or the inversion center) generate it in different orientations.

How Special is Chirality? Democratic Answer: Pretty special Class voted overwhelmingly that there should be more achiral than chiral molecules (Vox Populi, Vox Dei)

2 -D Chirality of Words Mirror by changing sign of X NOON MUM is not its own is its own mirror image. Thus it is “chiral” “achiral” like most or “meso” of the words.

2 -D Chirality of Words Rotate by changing signs of X and Y NOON does have rotational symmetry, but still it is chiral, like a propeller

2 -D Chirality of Words Mirror by changing sign of Y DECODE is also an “achiral” “meso” word, but it is harder to recognize, because horizontal mirrors are unfamiliar.

How Special is Chirality? Not at all. Almost all words are chiral. Achiral or meso words, such as MUM and DECODE are very rare. It is the same with molecules. Almost all molecules are chiral. (But when we deal with very simple molecules, we often encounter achiral or meso ones. )

Beyond Constitutional Isomerism (Stereochemistry) Isomers Composition Constitution Configuration Conformation distinction based on bonding model All "isomers" represent local energy minima (not just different phases of vibration) HARD Change requires breaking bonds (van't Hoff) "Stereoisomers" EASY Change by rotating about single bonds (Paternó)

Stereochemical Relationships Two molecules with the same constitution can be: Identical (Homomers) Completely Different Diastereomers Mirror Images Enantiomers

Facts Ideas Words (pictures too)

3 D Clues in Model Pictures Stereo, Rotation, Size, Perspective, Shading, Obstruction, Highlight, Wedge-Dash, etc.

End of Lecture 26 Nov. 5, 2008 Copyright © J. M. Mc. Bride 2009. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-Non. Commercial-Share. Alike 3. 0). Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol . Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. Mc. Bride, Chem 125. License: Creative Commons BY-NC-SA 3. 0