Top Banner
Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.
53

Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Dec 23, 2015

Download

Documents

Janice Campbell

chiral slide

light slide

meso slide

cis slide

rings slide

syn slide

carbohydrate slide

priorities slide

Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Stereochemistry

Stereochemistry refers to the 3-dimensional properties and

reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.

Page 2: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.
Page 3: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Definitions

• Stereoisomers – compounds with the same connectivity, different arrangement in space

• Enantiomers – stereoisomers that are non-superimposible mirror images; only properties

that differ are direction (+ or -) of optical rotation

• Diastereomers – stereoisomers that are not mirror images; different compounds with different physical properties

Page 4: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

More Definitions

• Asymmetric center – sp3 carbon with 4 different groups attached

• Optical activity – the ability to rotate the plane of plane –polarized light

• Chiral compound – a compound that is optically active (achiral compound will not

rotate light)• Polarimeter – device that measures the

optical rotation of the chiral compound

Page 5: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Plane-Polarized Light

Page 6: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Plane-Polarized Light through an Achiral Compound

Page 7: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Plane-Polarized Light through a Chiral Compound

Page 8: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Polarimeter Measures Optical Rotation

Page 9: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Specific Rotation, [α]

[α] = α / cl = observed rotation

c = concentration in g/mLl = length of tube in dm

Dextrorotary designated as d or (+), clockwise rotation

Levorotary designated as l or (-), counter-clockwise rotation

Page 10: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Specific Rotations of some Common Organic Compounds

Compound [] # * centers

Penicillin V +233.0 3

Sucrose +66.5 10 

Camphor +44.3 2

MSG +25.5 1

Cholesterol -31.3 8

Morphine -132.0 5

Page 11: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Chirality CenterCarbon has four different groups attached

Page 12: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Enantiomers nonsuperimposible mirror images

OH

CH3HO2CH

OH

CO2HCH3

H

mirrorplane

(S)(+) lactic acid (R)(-) lactic acid

from muscle tissue from milk[] = +13.5 [] = -13.5

oo

Page 13: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Enantiomeric Excess(Optical Purity)

actually 94.3% (+)

11.4% racemic88.6% (+)

= 88.6% e.e.

x 100 123.0109.0

e.e. =

oobserved rotation = +109

from oranges

o

[] = +123.0

H

from lemons

o[=

(S)-(-) Limonene (R)(+) Limonene

H

x 100 = enantiomeric excess (e.e.)rotation of pure enantiomerobserved rotation

Page 14: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.
Page 15: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Biological Activity

(R)(+) Thalidomide (S)(-) Thalidomide

N

NO

O

O

O

H

H

a sedative and hypnotic a teratogen

N

NO

O

O

O

H

H

Page 16: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

SSRI Efficacy depends on Stereochemistry

ON(CH3)2

F

NC

*

(+/-) Celexa(-) Lexapro

Page 17: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Absolute Configuration

1

23

4

Use Cahn, Ingold, Prelog priorities

Place the lowest priority group back (focus down C - 4 bond)

(R)

clockwise

draw arrow from 1-2-31

2 34

(S)

counterclockwise

Page 18: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Assign Priority to each Group on Asymmetric Center

focus down C-4 bond

4

3

2

1I

ClHF

rotateI

FH

Cl

Page 19: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Lactic Acid

(S) (R)

4

3 2

1

4

32

1OH

CH3 CO2HH

OH

CH3HO2CH

Page 20: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

C.I.P. Priorities

CH2CH2CH3 CH(CH3)2

CH2CH2OH CH2CH

O

CH2CH2CH3 CH=CH2

CO2H CH 2Cl

Low High

CH2CH2Br CH(CH3)2

Page 21: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Fischer Projections

Vertical bonds move away (dashed bonds)

Horizontal bonds approach you (wedge bonds)

OH

CO2H

CH3

HOH

CH3HO2CH

OH

CO2H

CH3

H

Page 22: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Assigning Absolute Configuration to Fischer

Projections

OH

CO2H

CH3

H

OH

CO2H

CH3

H

OH

CH3HO2CH

(S) (S) (S)rotate

Page 23: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Rotation of the Projection 90o

Reverses Absolute Configuration

90o

90oo

90

(S) (R) (S) (R)

CH3

H

OH

HO2C

CO2H

CH3

H

HO

H

OH

CO2H

CH3

OH

CO2H

CH3

H

Page 24: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

DiastereomersStereoisomers That Are Not Mirror Images

3 322

opposite stereochemistry at C3

same stereochemistry at C2 (S)

CO2H

OHH

Br H

CO2H

OHH

BrH(2S,3S) (2S,3R)

Page 25: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Fischer Projections with 2 Chiral Centers

CO2H

CH3

H OH

Br H H Br

H OH

CO2H

CH3

(2S,3S) (2S,3R)

2

3

2

3

Page 26: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

2 Chiral Centers4 Stereoisomers

Page 27: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Identical, Enantiomers or Diastereomers?

H

H

CH3

CH3

&

CH3

CH3

H

H CC

a)

CH2CH3

CH3

H

H

Br

Br

CH2CH3

CH3&

b)

OH

HO

NH2

NH2

Page 28: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Tartaric Acids

CO2H

CO2H

H OH

HO H H OH

HO H

CO2H

CO2H

CO2H

CO2H

H OH

H OH HO H

HO H

CO2H

CO2H

R,R S,S

R,S S,R

Page 29: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Racemic Mixture

o

(g/mL) 1.7598 1.7598 1.7723

m.p. C 168-170 168-170 210-212

[] (degrees) - 12 + 12 0

(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid

Racemic Mixture (Racemate): 50/50 mixture of enantiomers

CO2H

CO2H

H OH

HO H H OH

HO H

CO2H

CO2H

R,R S,S

Page 30: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Meso CompoundInternal Plane of Symmetry

Optically Inactive

orotate 180

superimposible

CO2H

CO2H

H OH

H OH HO H

HO H

CO2H

CO2H

R,S S,R

mirror plane

Page 31: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

2,3,4-trichlorohexaneHow many stereoisomers?

Cl

Cl

Cl3 asymmetric centers

8 stereoisomers

* **

2n, n= # asymmetric centers (3)

Page 32: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

n = 3; 2n = 8

CH3

CH2CH3

H Cl

Cl H

H Cl Cl H

H Cl

Cl H

CH3

CH2CH3

CH3

CH2CH3

Cl H

H Cl

H Cl Cl H

Cl H

H Cl

CH3

CH2CH3

H Cl

H Cl

H Cl

CH3

CH2CH3

Cl H

Cl H

Cl H

CH3

CH2CH3

Cl H

H Cl

H Cl

CH3

CH2CH3

H Cl

Cl H

Cl H

CH3

CH2CH3

S

S

R

R

R

S

Page 33: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

A CarbohydrateCHO

CH2OH

H OH

HO H

H OH

H OH

(+) D-Glucose

R

S

R

R

Page 34: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Internal Planes of Symmetry

CH3CH3

CH3CH3

CH3CH3

CH3 CH3

Both are Meso

Page 35: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Asymmetric Centers on Rings

Br

Br

Br

Br

1(R),2(S) cis 1,2-dibromocyclohexane

nonsuperimposible but A flips into B

A B

BrBr

Meso

Page 36: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Allenes can be Chiral

C C C

H

CH3

C CClHC

CH3

H

ClH

Page 37: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Mycomycin, an antibiotic

C C C

H

CH=CHCH=CHCH2CO2HCCCCHH

Nocardia acidophilus []D = -130o

Page 38: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Reactions that Generate Chirality Centers

Hydrogenation, syn

CH3CH3

CH2CH3CH2CH3

H2, Pt/C

CH2CH3 CH2CH3

CH3CH3

HH

CH2CH3

CH2CH3

H CH3

H CH3

product is meso

Page 39: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

BrominationTrans is formed exclusively

No Meso is formed (cis)

racemic mixture

S SR RBr BrBr Br

Br2

Page 40: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Bromonium Ion is Opened Equally from Both Sides

Br2

Br Br Br BrR R S S

racemic mixture

Br

Br

Br

Br

Br Br + -

Page 41: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

trans alkene + anti addition = MESO

CH2CH3

CH2CH3 H

H

Br2

CH2CH3

CH2CH3

HH

Br

Br

Br Br

CH2CH3CH2CH3HH

meso

Page 42: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

cis Alkene + anti addition = racemic mixture

H

CH2CH3 CH2CH3

H

Br2

Br Br

CH2CH3CH2CH3 H

HR R

CH2CH3

CH2CH3

H

H

Br

Br

CH2CH3CH2CH3 H

H

Br BrS S

Br

H HCH2CH3CH2CH3

Br

Br

BrH

H

CH2CH3

CH2CH3

a b

a b

Page 43: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Brominations Often Generate Asymmetric Centers

Br2

R RS S

racemic mixture

CH3CH3

H H

CH3CH3

Br BrH H

CH3CH3

Br BrH H

CH3

CH3 H

H CH3

CH3 H

H

Br

Br

CH3CH3

Br BrH H

S Rmeso

Br2

Page 44: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Asymmetric Center is Generated Racemic Mixture Formed

H-Br

HH

Br

Br

a)

b)

Br

H

a) Br

H

b)(R) (S)

Page 45: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Asymmetric Induction

PPh2

PPh2

RuCl2

CH3

OHH2

Ru(BINAP)Cl2

CH3H

OH

96% e.e.

Noyori and Knowles shared Nobel Prize in Chemistry, 2001

Page 46: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Preparation of (L)-Dopafor Treatment of Parkinson’s

HO

HO

CH2C

CO2H

NH2

H

l-(-) Dopa

HO

HO

CH2CH2NH2

Dopaminecannot cross blood-brain

barrier

C=CNH2

CO2HH

HO

HO

H2Rh(DIOP)Cl2

enz.

Page 47: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Relevance of Stereochemistry

(S,S)(R,S)useful decongenstants

d-pseudoephedrine and l-ephedrine

4 stereoisomers

**

2 asymmetric centers

EPHEDRA from Ma Huong

NHCH3

CH3

OH

Page 48: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

One-step synthesis

Pseudophed

*

d-(S)- "Meth"l-(R) - Vicks

(methamphetamine)"desoxyephedrine"NHCH3

CH3

Page 49: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

-(p-isobutylphenyl)propionic acid

CH3 CO2HH

(S)(+) ibuprofen (R)(-) ibuprofen

CH3HO2C

H

anti-inflammatory 80-90% metabolized to (S)(+)

Page 50: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Model of Thalidomide

Page 51: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

How Sweet it is!

Sucrose

O

HOOH

O

CH2OH

OCH2OH

CH2OH

HO

HO

OH

Sucralose or Splenda

O

Cl

HOOH

O

CH2OH

OCH2Cl

CH2Cl

HO

HO

Sucralose is 600 times sweeter and does not get metabolized.

Page 52: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Sildenafil (Viagra) and Caffeine

NN

N

N

CH3

H

O

CH3CH2O

S

N

N

CH3

O

O

N

N

N

N

CH3

O

O

CH3

CH3

Page 53: Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned.

Radiosensitizer of Choice Until 2004

Okadaic acid17 asymmetric centers

O

OH

HOOC

OH

OH

O

OH

HO

OH

HOH

O

O


Related Documents
Chapter 9: Stereochemistry 31 summer 14...Stereochemistry Vocabulary Enantiomers = non- superimposable mirror images (stereoisomers) Chiral molecules = molecules th t t i blthat are

Chapter 9: Stereochemistry 31 summer 14...Stereochemistry...

Category: Documents
STEREOCHEMISTRY OF ALKANES AND … · CONFORMATIONAL ISOMERS •Stereochemistry concerned with the 3-D aspects of molecules •Rotation is possible around C-C bonds in open-chain

STEREOCHEMISTRY OF ALKANES AND … · CONFORMATIONAL...

Category: Documents
Stereochemistry - Elsevier · 2014-06-26 · 241 8 stereochemistry 8.1 stereoisomers 8.2 mirror image objects, mirror image molecules, and chirality Molecules that have different

Stereochemistry - Elsevier · 2014-06-26 · 241 8...

Category: Documents
Module 8 Stereochemistry Lecture 20 Stereochemistry I

Module 8 Stereochemistry Lecture 20 Stereochemistry I

Category: Documents
STEREOCHEMISTRY · 2021. 1. 15. · Scope • Stereochemistry (from the Greek stereos, meaning solid) refers to chemistry in space i.e., in three dimensions and describes chemistry

STEREOCHEMISTRY · 2021. 1. 15. · Scope •...

Category: Documents
Stereochemistry of small molecules: Configurational and ...Stereochemistry of small molecules: Configurational and conformational control Yiqun Zhang Dissertation submitted to the

Stereochemistry of small molecules: Configurational and...

Category: Documents
Stereochemistry: Chiral Molecules

Stereochemistry: Chiral Molecules

Category: Documents
Stereochemistry Chiral Molecules · Ch. 5 - 4. 1A. The Biological Significance of Chirality Chiral molecules are molecules that cannot be superimposable with their mirror images.

Stereochemistry Chiral Molecules · Ch. 5 - 4. 1A. The...

Category: Documents
Stereochemistry Importance of Stereochemistry€¦ · 1 Stereochemistry The Relative Arrangement of Atoms in Space Stereochemistry •Stereochemistry: –The study of the three-dimensional

Stereochemistry Importance of Stereochemistry€¦ · 1...

Category: Documents
Stereochemistry & Chiral Molecules. Isomerism Isomers are different compounds with the same molecular formula 1) Constitutional isomers: their atoms are.

Stereochemistry & Chiral Molecules. Isomerism Isomers are...

Category: Documents
Definitions o Stereochemistry refers to the 3-dimensional properties and reactions of molecules. o It has its own language and terms that need to be learned.

Definitions o Stereochemistry refers to the 3-dimensional...

Category: Documents
© 2013 Pearson Education, Inc. Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language.

© 2013 Pearson Education, Inc. Stereochemistry...

Category: Documents