ISOMERS

(same no. and kinds of atoms, but dif fer in the way the atoms are arranged, dif ferent compounds with the same molecular f ormula )

LMZ/CHEM109A/ Winter 2010

4. Fisher Projections (Sec 5.5) A tetrahedral carbon atom is represented in Fischer projection by two crossed lines. By convention, the horizontal lines represent bonds coming out of the page, and the vertical lines represent bonds going into the page.

Constitutional (or structural) Isomers

(dif f erent connections of atoms; dif f erent bonding sequence) (sec. 2.8)

Stereoisomers
(same connections of atoms but diff erent 3-D arrangement in space)

Same f unctional group, but diff erent carbon skeleton

diff erent f unctional groups

diff erent positions of f unctional group

(Sec. 2.8) geometric isomers ( or cis-trans isomers)

enantiomers (Chap. 5)

e.g. C5H12
CH3 CH2 CH2 CH3 H3C C CH3 CH3 CH2 CH3 H3C HC CH3 CH3 CH2

e.g. C2H6O
H H H C C OH H H H H H

e.g. C3H8O
OH H H H C C C H H H H H OH H C C C H H H H

e.g. A
H

B H
Cl Cl H

A H

H B
Cl H Cl H

diastereomers (Chap. 5)

cis-isomer

trans-isomer

5. Asymmetric center and stereocenters (stereogenic centers) - Asymmetric center: chiral carbon center - stereogenic center: stereoisomers formed when two substituents interchanged.

H C O C H H H

cis-isomer

trans-isomer

Chapter 5 Stereochemistry I. Chiral Compounds and Enantiomers (Sec. 5.2-5.3) 1. Molecules that are not superimposable on their mirror images and thus exist in two enantiomeric forms (enantiomers) are said to be chiral.
A D C B mirror images B A D C

2. A molecule is chiral when there is no plane of symmetry in the molecule (i.e. no imaginary plane that can cut through the molecule so that one half of molecule is not the exact mirror image of the other half--- note: the molecule can rotate) 3. A carbon atom bonded to four different groups is called a chiral (asymmetric) center. (NOTE: Molecules that possess chiral carbons are usually chiral. Exception: mesocompound or a compound that have a plane of symmetry) Which of the following compounds are chiral? Identify the meso compound(s).
e.g. 1 CH3 H HOOC H H HOOC e.g. 2 CH3 OH e.g. 3 H CH3 e.g. 4 H CH3 O e.g . 5 Br H Cl Br H Cl

II. Sequence Rules (Cahn-Ingold-Prelog Rules) for Specification of Configuration (Sec. 5.7) - a verbal method for indicating the 3-D arrangement of atoms (the configuration) at the stereogenic (chiral) center 1. Look at the four atoms directly attached to the chiral center, - assign priorities in order of decreasing atomic number e.g.1 , I > Br > Cl > S > F > O > N > C > 3H (T) > 2H (D) > 1H - the group with the highest atomic number is ranked first; the group with the lowest atomic number is ranked fourth Br e.g. 3 e.g. 2 Br
Cl H CH3
H CH3 CH2CH3

2. If a decision about priority can't be reached by applying rule 1, compare atomic numbers of the second atoms in each substituent, - continuing on as necessary through the third or fourth atoms outward until the first point of difference is reached. - one high-priority atom takes priority over any number of lower-priority atoms
e.g. 4 H C Br H H CH3 H H H

>

C Cl Cl

>

C CH3 CH3

>

C CH3 CH3

>

C CH3 H

>

C H H

e.g. 5

CH3 C CH3 CH3

CH2Br

CH2Br

CH3

>

C CH3 H

>

C H H

>

C H H

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3. Multiple-bonded atoms are considered as an equivalent number of single-bonded atoms

e.g. 6 OH C O
becomes

mirror H COOH OH C C A H OH COOH HO OH COOH H C C H COOH B C H

OH C O C N
becomes

(N) (C) C N (N) (C)

COOH OH C C

mirror OH COOH H C C H OH COOH D

(O) (C)

OH

e.g. 7
HO

COOH CH3 H

e.g. 8
HOH2C OHC

H OH

H COOH

4. Mentally orienting the molecule so that the group of lowest priority (fourth) is pointing directly back, away from us. Look at the three remaining substituents, if a curved arrow drawn from the highest to the second-highest to third-highest priority substituent (123) is clockwise, we say that the chiral center has the R configuration; if it is counterclockwise, we say that the chiral center has the S configuration. If a molecule has R configuration, its mirror image must have S configuration.

Which of the compounds above are meso- compounds? Relationships between A and B: C and D: A and C or D: B and C or D: C. Chirality of Conformationally Mobile Systems A molecule cannot be optically active if its chiral conformations are in equilibrium with their mirror images. We consider such a molecule to be achiral. Which of the following compounds is chiral?
Br Br
cis-1 ,2 -d ib ro m o c y clo h e xa n e

Br Br

H Br Br Br H

H Br H Br

H Br H Br

H Br Br H

III. Molecules with Two or More Chiral (Stereogenic) Centers (Sec. 5.11) A. In general, a molecule with n stereogenic centers gives rise to a maximum of 2n stereoisomers (2n-1 pairs of enantiomers). (Exception: meso compounds).
H COOH NH2 C C H CH3 A H H2N C C HO H CH3 H3C COOH HOOC OH HO CH3 B H C C OH H H3C NH2 H2N C H C C OH H HO H mirror H2N COOH H C C H OH CH3 H COOH NH2 C C H H CH3 D H C C CH3 NH2 mirror H2N COOH H C C OH

Br

Br

Br

t r a n s -1 ,2 -d ib ro m o cy c lo h e xan e

D. Nomenclature (sec. 5.13) - the configuration of each chiral center is individually determined.

COOH HOOC

Relationships between A and B: C and D: A and C or D: B and C or D: Enantiomers: stereoisomers that are not superimposable on their mirror images; enantiomers have opposite configuration at all stereogenic centers. Diastereomers: stereoisomers that are not identical and are not mirror images of each other; diastereomers have the same configuration in at least one center but opposite configurations at the others. B. Meso Compounds (Sec. 5.12) - compounds with two or more stereogenic centers, but achiral due to the presence of a symmetry plane

IV. Optical Activity and Racemic Mixtures (Sec. 5.8-5.10 ) 1. Plane-polarized light: light waves oscillating in a single plane (Fig 5.13) 2. Chiral compounds can rotate the plane polarized light - optically active 3. Polarimeter - intrusment for measuring the amount of rotation. (Fig. 5.12) a) plane-polarized light pass through the solution of optically active compound and the rotation of the plane of the polarized light occurs b) by rotating the analyzer until the light passes through it, we can find the new plane of polarization and the extent of rotation () c) levorotatory compounds: rotate polarized light to the left: (observing directly end on at the analyzer) -- minus sign (-) dextrorotatory compounds: rotate polarized light to the right, plus sign (+) NOTE: (i) The sign of optical rotation, (+) or (-), is not related to the R, S designation. -- the R, S configuration is designated from the arrangements of groups in space -- the optical rotation (+) or (-) is determined experimentally i.e. A chiral compound of R configuration can be (+) or (-) in optical activity,

LMZ/CHEM109A/ Winter 2010

-- if a chiral compound of R configuration is (+) in optical activity, its mirror image (enantiomer, S configuration) will be (? ) in optical activity. (ii) A racemic mixture or racemate (an equal (1:1) mixture of two enantiomers) show zero rotation. Why? (iii) What about the optical rotation of achiral compounds or meso- compounds? d) specific rotation: -- the amount of rotation depends on the number of molecules that the light beam encounters, and therefore depends on the concentration of the sample and the path length (length of sample tube in the direction of light) -- to standardized, specific rotation []D is used path length: l = 1 dm (10 cm); light: = 598 nm (sodium D line); sample conc.: c = 1 g/mL - at 25C []25D = Observed rotation (degrees)_______ = /lc path length l (dm) x conc. c (g/mL) e.g. A 1.5 g sample of compound A was dissolved in 10 mL ethanol and placed in a sample cell with a 5.0 cm path length. The observed rotation at the sodium D line was 1.2. Calculate the specific rotation []D for compound A. e) enantiomeric excess e.e. = observed specific rotation/specific rotation of the pure enantiomer x 100% V. Physical Properties of Stereoismer and Pasteur's Discovery of Enantiomers (Sec. 5.16) 1. Enantiomers: same melting points, boiling points, solubilities, chemical propertiesexcept for reactions with chiral compounds. - differs in the sign of their rotation of plane-polarized light. 2. Diastereomers: different properties 3. Racemic mixture or racemate: - acts as a pure compound, but their physical properties are different from either of the enantiomers due to different packing and intermolecular interactions. 4. Pasteur found that sodium ammonium tartrate formed two distinct kinds of crystals (1849).
COO H C C OH COO H H COO OH OH C C OH COO H

- compounds with a lone electron pair N is a chiral (asymmetric center), but inversion fast (racemization) ~6 kcal/mol

VI. Stereochemistry of alkene reactions

a) The two kinds of crystals were different in shapes and nonsuperimposable mirror images of each other. b) The solutions of the crystals of either kind (+) or (-) were optically active, but solutions of the orginal salt (), (a 50:50 mixture of each kind) was optically. VI. N atom can be asymmetric centers (sec. 5.17) - compounds with four different groups attached.