Chem 125 Lecture 2611/5/08

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van't Hoff’s Optically Active Compounds

Malic Acid (CO2H)CH(OH).CH2. (CO2H)

Lactic Acid (CH3)CH(OH)(CO2H)

Tartaric Acid (CO2H)CH(OH).CH(OH)(CO2H)

Aspartic Acid (CO2H)CH(NH2).CH2. (CO2H)

Amyl Alcohol (CH3)(C2H5)CH(CH2OH)

Glucose COH(CHOH)4CH2(OH)(Levulose, Lactose)

Maleic & Fumaric Acids(CO2H)HC=CH(CO2H)

(CO2H)CH2CH2(CO2H)Succinic Acid

HI/P OH H “reduction” (Bremer & van't Hoff)

& Most of theirDerivatives, but not

inactive

ScheeleLiebigWislicenus

(Scheele, Berzelius, Pasteur, Wislicenus)

right, left, and inactive

Encyclopaedia Britannica, 1911:LACTIC ACID (hydroxypropionic acid), C3H6O3. Two lactic acids are known, differing from each other in the position occupied by the hydroxyl group in the molecule; they are known respectively as -hydroxypro-pionic acid (fermentation, or inactive lactic acid), CH3CH(OH) . CO2H, and 3-hydroxypropionic acid (hydracrylic acid), CH2(OH)CH2CO2H. Although on structural grounds there should be only two hydroxypro-pionic acids, as a matter of fact four lactic acids are known . The third 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 ammonium lactate.

Constututional Isomers

It is identical with -hydroxypropionic acid in almost every respect, except with regard to its physical properties. The fourth isomer, formed by the action of Bacillus laevo-lacti on cane-sugar, resembles sarcolactic acid in every respect, except in its action on polarized light.

“…the fancy trifles in it are totally devoid of any factual reality…” Kolbe on van’t Hoff (1877)

!

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!”

(CO2H)CH2CH2(CO2H)Succinic Acid

“reduction” (Bremer & van't Hoff)& Most of theirDerivatives, but

inactive

van't Hoff’s Optically Active Compounds

Malic Acid (CO2H)CH(OH).CH2. (CO2H)

Lactic Acid (CH3)CH(OH)(CO2H)

Tartaric Acid (CO2H)CH(OH).CH(OH)(CO2H)

Aspartic Acid (CO2H)CH(NH2).CH2. (CO2H)

Amyl Alcohol (CH3)(C2H5)CH(CH2OH)

Glucose COH(CHOH)4CH2(OH)(Levulose, Lactose)

Maleic & Fumaric Acids(CO2H)HC=CH(CO2H)

"Every carbon compound which in solution can rotate the plane ofpolarized light contains one or more asymmetric carbon atoms."

van’t Hoff Cardboard

Models(Bremer’s set, in Museum Boerhaave, Leiden)

(from T. M. van der Spek, Annals of Science, 2006)

Colored Faces

Colored Vertices

Ladenburg Benzenes

Maleic and Fumaric Acids

Free Rotation : Tartaric / meso

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 R1,R2,R3 (and R4,R5,R6) can be arranged clockwise or counterclockwise about the C-C axis. This sequence is permanent and unaffected by C-C rotation. If R 1=R4, R2=R5, R3=R6, 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.

van’t Hoffpredicts

handedness 1874

C10H7

C6H5

C6H5

C10H7

61 years after

van’t Hoffprediction

of 1874

C6H5

OCOCH2COOH

C C C

C6H5

C10H7

C10H7

C6H5

tetrahedralbonds

coplanarbonds?

must break bond to

isomerize to mirror image

C6H5

OCOCH2COOH

C C C

C6H5

C10H7

Isomer Numbers for “Dewar's” 3D Benzene Structures

C

C

C

CC

C

H H

HH

H

H

"Prismane"or

"LadenburgBenzene"

"Dewar Benzene"

C

C

H H

C

C

C C

H HHH

C C

CC

C

CHH

H H

H H

C C

C

C

C C

H

H

H

H

H

H

C C

CC

CC

HH

H H

HH

C C

C C

CC

HH

H HHH

C

C

H H

C

C

CC

H

HH

H

2(1)

3(2)

3(1)6(3)

3(3)

5(4)3(2)

19(6)

2(1)

3(2)

3(1)6(3)

2(1)

5(3)1

6(3)

2(1)

3(2)3(1)

6(3)

3(2)

25(2)

1

3(1)

MONO

DI

(additional number if mirror-images count for these nonplanar structures)

(subtotals with total in Red)

3(1)assuming

free rotationof CH3

0top

0mid

0bottom

0total

?

which our intuition interprets as rotation about the vertical axis (exchanging right and left), because people pivot, but don’t "invert".

It exchanges front and back,

Mirror Images

Q. Why does a mirror exchange right . and left, but not top and bottom?

A. Actually it changes neither.

Right

is Top

on top

is on right

special.lib.gla.ac.uk/ exhibns/month/mar2000.html

Right Arm

Oxford Mathematician

blind in one eye

special.lib.gla.ac.uk/ exhibns/month/mar2000.html

Right ArmLeft Arm

“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…

"Now, if you'll only attend, Kitty, and not talk so much, I'll tell you all my ideas about Looking-glass House…

"How would you like to live in Looking-glass House, Kitty? I wonder if they'd give you milk, there?

“Perhaps Looking-glass milk isn't good to drink.

E. Heilbronner, J.D. Dunitz, Reflections on Symmetry, 1993, p. 86

(sarcolactic?)

“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 “” hand)

Chirality (Greek “” hand)Change Sign of all

X Coordinates?

Reflection in yz MirrorChange Sign of all

Y Coordinates?

Reflection in xz MirrorChange Sign of all

Z Coordinates?

Reflection in xy MirrorChange Sign of all X & Y Coordinates?

Rotation about z AxisChange Sign of all X & Z Coordinates?

Rotation about y AxisChange Sign of all Y & Z Coordinates?

Rotation about x AxisChange 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 Specialis Chirality?

Democratic Answer:Class voted overwhelmingly that there should be

more achiral than chiral molecules

(Vox Populi, Vox Dei)

Pretty special

2-D Chirality of Words

MUMis its own

mirror image.Thus it is“achiral”or “meso”

Mirror bychangingsign of X

NOONis not its ownmirror image.

Thus it is“chiral”

like mostof the words.

2-D Chirality of WordsRotate bychangingsigns ofX and Y

NOONdoes have rotationalsymmetry,but still itis chiral,

like a propeller

2-D Chirality of Words

DECODEis also an“achiral”

“meso” word,but it is harderto recognize,

because horizontal mirrors areunfamiliar.

Mirror bychangingsign of Y

How Special is Chirality?

Almost all words are chiral.

Achiral or meso words, such asMUM and DECODE are very rare.

It is the same with molecules.

Almost all molecules are chiral.

Not at all.

(But when we deal with very simple molecules,we often encounter achiral or meso ones.)

Beyond Constitutional Isomerism(Stereochemistry)

Composition

Constitution

"Stereoisomers"

distinction based onbonding model

Change requires breakingbonds (van't Hoff)

Change by rotatingabout single bonds

(Paternó)

Isom

ers

Configuration

Conformation

HARD

EASY

All "isomers" representlocal energy minima

(not just differentphases of vibration)

Stereochemical Relationships

Two molecules with the same constitution can be:

Identical

Completely Different

Mirror Images

(Homomers)

Diastereomers

Enantiomers

Facts

Ideas

Words (pictures too)

3D Clues in Model PicturesStereo, Rotation, Size, Perspective, Shading,

Obstruction, Highlight, Wedge-Dash, etc.

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

End of Lecture 26Nov. 5, 2008