Introduction to stereochemistry, Representation of 3D molecules, R/S nomenclature, D-L and M-P convention, Topicity, Prochirality, Allenes, Biphenyls, Spiranes, Hemispirane.
PTC IS THE PHASE TRANSFER CATALYSIS HERE TYPES OF PTC ARE DISCUSSED , THEORIES OF CATALYSIS AND MECHANISM OF PTC, ADVANTAGES OF PTC, APPLICATION OF PTC
PTC IS THE PHASE TRANSFER CATALYSIS HERE TYPES OF PTC ARE DISCUSSED , THEORIES OF CATALYSIS AND MECHANISM OF PTC, ADVANTAGES OF PTC, APPLICATION OF PTC
Cyclohexane exists in different conformations viz chair, boat, twist boat and half chair. These conformations possess different energies. Therefore they differ in energy.
In 1891,Emil fischer devised a method of representing the 3D structures of
molecules in 2D Structures on a plane (Paper) by convention, horizontal line
represent bonds projecting from the plane of paper towards the observer and
vertical line represent away from the observer
Cyclohexane exists in different conformations viz chair, boat, twist boat and half chair. These conformations possess different energies. Therefore they differ in energy.
In 1891,Emil fischer devised a method of representing the 3D structures of
molecules in 2D Structures on a plane (Paper) by convention, horizontal line
represent bonds projecting from the plane of paper towards the observer and
vertical line represent away from the observer
Chirality and its biological role (English language) - www.wespeakscience.comZeqir Kryeziu
This presentation focuses on organic chemistry, especially stereochemistry for 3D shape of molecules. When the same chemical substance differs in its spatial construct it changes in a drastic way its own features, in a biological environment.
Theories of coordination compounds, CFSE, Bonding in octahedral and tetrahedral complex, color of transition metal complex, magnetic properties, selection rules, Nephelxeuatic effect, angular overlap model
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 2
HISTORY:
Christian Huygens (1629-1695) discovered plane polarized light.
Jean Baptiste Biot in 1815 noted that certain natural organic compounds rotate plane
polarised light.
Louis Pasteur in 1847 carried out crystallization of sodium ammonium salt tartaric acid and
separated mirror image crystals by hand. The equimolar solution of separated crystals have
equal but opposite optical activity.
In 1847 Joseph A Lebel and Jacobs H Van’t Hoff proposed carbon with four attachment is
tetrahedral and showed that carbon with four different attachments may exists as a pair of
isomers.
Thalidomide disaster showed significance of stereochemistry. This drug was used to treat
morning sickness in pregnant women. However, drug caused deformation in babies. It was
3. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 3
found that one isomer was safe but other had tetratogenic (agent that disturb development of
embryo) effect causing serious genetic damage.
Acts as Sedative Acts as Tetratogenic
R-(+)-Thalidomide S-(-)-Thalidomide
What is Stereochemistry?
It is branch of chemistry that involves the study of the different spatial orientation or
arrangement of atoms or groups in the molecule.
This branch of chemistry is commonly referred to as 3-Dimensional chemistry. Since, it
focuses on stereoisomers (i.e. chemical compounds with same molecular formula but
different spatial arrangement in three dimensions).
Enantiomers - Non-superposable mirror images or chiral molecules which are mirror
images.
Enantiomers have identical: b.p.’s, m.p.’s, solubilities, index of refraction, IR, NMR in
achiral solvent, etc.
Enantiomers differ when they interact with other chiral substances and when they interact
with plane polarized light
Chiral or asymmetric carbon - a tetrahedral carbon atom bearing four different
substituent’s.
Diastereomers - stereoisomers which are not enantiomers (or mirror images), that is non-
super imposable not mirror images.
Diastereomers have different physical properties.
Optical activity - the ability of chiral substances to rotate the plane of polarized light by a
specific angle
4. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 4
Racemic mixture - an equimolar (1:1) pair of enantiomers is called a racemic mixture. A
racemic mixture has an optical rotation of zero.
Device used to measure optical rotation: Polarimeter
Dextrorotatory (+): an optically active compound that rotates plane polarized light in a
clockwise direction.
Levorotatory (-): an optically active compound that rotates plane polarized light in a counter
clockwise direction.
The specific rotation of a compound is calculated using the following formula:
Molecules with one stereocenter can be R or S = 2 possible stereoisomers.
Molecules with n stereocenters can have all the possible combination of R and S for each
stereocenter = 2n
possible stereoisomers.
Representation of three dimensional molecules
Configuration of a chiral molecule is three dimensional structure and it is not ver easy to
depict on a paper having only two dimensions. To overcome this problem four 2dimesional
structures known as projections have been used.
(1)Dashed Wedge or Flying Wedge formula
(2)Fischer projection
(3)Sawhorse formula
(4)Newmann projection.
5. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 5
(1)Dashed-Wedge or Flying Wedge formula
In this representation a solid continuous lines represent bond is in the plane.
A solid wedge line represent bond is above the plane i.e. towards the observer.
( )
A broken wedge / dashed line represent the bond is below the plane i.e. away from the
observer.
( )
CH3
H
OH
CH2CH3
CH3
H
OH
CH2CH3
Dash-Wedge formula
(2) Fischer projection:
In this representation, bonds are drawn as solid lines. The bonds are placed vertical and
horizontal to each other.
A tetrahedral carbon is represented using just two crossed lines represents the stereo center.
6. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 6
Horizontal line is coming out of the plane of the page (towards observer) and vertical line is
going back behind the plane of the paper (away from observer).
In Fischer representation most oxidized carbon atom is placed on the vertical line at the top.
COOH
CH3
NH2H
D-Alanine
Most oxidize carbon
COOH
CH3
NH2H
D-Alanine
There are some regular relationships that are "short cuts" to recognizing stereochemical
relationships:
• A 180° rotation gives the same stereochemistry.
7. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 7
• A 90° rotation gives the inverted stereochemistry.
• Exchanging any two positions gives the inverted stereochemistry.
• Pairwise exchange of two sets of positions gives back the same stereochemistry.
Disadvantage:
➢ These projections can be turned or rotated only in certain specified way.
➢ In compounds more than one stereocenters, a Fischer projection implies an eclipsing
relationship of groups attached to two stereo centers but staggered is more stable than
eclipsed.
(3) Saw-horse representation
In this representation each carbon atoms may be viewed as a letter “Y”.
CHO
OHH
CH2OH
H Cl
Front carbon
Rear carbon
H Cl
CH2OH
H OH
CHO
8. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 8
CHO
OHH
CH2OH
H Cl
1
2
3
4 4
3
2
1 CH2OH
CHO
4
3
2
1
Cl
CH2OH
H OH
CHO
4
3
2
1
HCl
CH2OH
4
3
2
1
H
CHO
HO H
EclipsedStaggered
Fischer projection
Sawhorse projection
Rotate C-2
by 180o
(4) Newmann Projections
In this representation the molecule is viewed along the bond joining the two carbon atoms.
The front carbon shown by three solid lines i.e. “Y”
The rear carbon is shown by a circle with three bonds pointing out from it i.e.
Combining the front and rear results in the eclipsed Newmann projection which on rotation
through 180o
results in stable staggered Newmann projection
9. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 9
StaggeredEclipsed
Newmann projection
Propane staggered Newmann projection from two views is shown below.
INTER CONVERSION OF REPRESENTATIONS
Conversion of Dash Wedge formula to Fischer projection
By viewing the molecule in between dash line and wedge line one can convert Dash formula
to Fischer projection as shown below
A
D
C B
A
B
D C
10. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 10
COOH
H
HO CH3
COOH
CH3
H OH
One more method for converting the dash formula into Fischer projection is to see whether
the solid continuous line is left or right side as follows.
If the solid lines are on right side in the first step solid line is written vertical line. In the
second step horizontal line is drawn and substituent which is placed on wedge bond will be
placed on right side.
CH3
CHO
Br
H
Right side CH3
CHO
CH3
CHO
HBrStep-1 Step-2
NOTE: Finally look for whether the most oxidized carbon is placed on top of the vertical
line. If not rotate the Fischer projection through 180o
in the plane of the paper.
11. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 11
CH3
CHO
Br
H
Right side CH3
CHO
CH3
CHO
HBrStep-1 Step-2
CH3
CHO
H Br
Rotate 180o
in the
plane of the paper
If the solid lines are on left side in the first step solid line is written vertical line. In the
second step horizontal line is drawn and substituent which is placed on wedge bond will be
placed on left side.
COOH
H
Left side COOH
NH2
COOH
NH2
CH3HStep-1 Step-2
H2N
CH3
Conversion of Fischer projection to Dash Wedge formula
The reverse of the above discussed method will be used to covert Fischer projection to Dash
Wedge formula.
In this conversion first step is Fischer vertical line will be written in solid line of Dash
formula. In the second step horizontal line will be written in dashed line and wedge line. To
place the substituent on dash and wedge line configuration of Fischer projection is used.
12. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 12
Left side
COOH
NH2
CH3H
Step-1
COOH
H2N Step-2
COOH
HH2N
CH3
(S)-Alanine (S)-Alanine
COOH
NH2
(S)-Alanine
COOH
NH2
H
H3C
Step-1
Step-2
Right side
Conversion of Fischer projection to Newmann projection to Sawhorse
formula:
Fischer projection is viewed either from front carbon or rear cabon atom which results in
eclipsed Newmann projection. Rotation of either front carbon or rear carbon 180o
gives
staggered Newmann projection. This Newmann projection viewed through central bonds
results in sawhorse formula.
13. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 13
Conversion of Sawhorse formula to Newmann projection to Fischer
projection:
Staggered Sawhorse formula is viewed either from front carbon or rear cabon atom which
results in staggered Newmann projection. Rotation of either front carbon or rear carbon 180o
gives eclipsed Newmann projection. This Newmann projection holding in vertical plane
results in Fischer projection.
Conversion of Sawhorse formula to Fischer projection:
Staggered Sawhorse formula is converted into eclipsed projection by rotating either front
carbon or rear carbon 180o
. It is then held in vertical plane in such manner that the two
groups pointing upwords are shown on the vertical line results in Fischer projection.
14. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 14
Configuration: Three dimensional arrangements of atoms or groups around an asymmetric
carbon atom or chiral centre are known as configuration.
Two systems have been developed to study the configuration of organic compounds.
(1) Relative configuration (D-L configuration): Prior to 1951, there was no method
available for determining the absolute configuration of a compound. So, configuration
relative to that of standard ((+)-Glyceraldehyde) were determined. This system of
configuration is known as D-L configuration.
CHO
CH2OH
OHH H
CH2OH
HO
CHO
D-Glyceraldehyde L-Glyceraldehyde
(2) Absolute Configuration (R-S system): Due to some draw backs of D-L configuration
a new system called R-S system of configuration was developed by Robert. S. Cahn
(Royal Institute of Chemistry, London), Christopher K. Ingold (University College,
London), and Vladimir Prelog (Swiss Federal Institute of Technology, Zurich) in the
1950's, and is thus called the Cahn-Ingold-Prelog convention.
D-L Conventions:
D-L system is seldom used today except for some class of compounds like carbohydrates and
amino acids.
D- & L - Glyceraldehyde are used as standard references for D-L system of configuration of
carbohydrates.
D- & L - Alanine are used as standard reference for alpha amino acid with D-L system of
configuration.
D-series of sugars are those with –OH group attached to highest numbered stereo center on
the right side in Fischer projection.
15. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 15
CHO
CH2OH
OHH
D-Glyceraldehyde
CHO
H OH
HO H
H OH
H OH
CH2OH
D-Glucose
CHO
HO H
HO H
H OH
H OH
CH2OH
D-Mannose
1
2
3
4
5
6
1
2
3
L-series are those with –OH group attached to highest numbered stereo center on the left side
in Fischer projection.
H
CH2OH
HO
CHO
L-Glyceraldehyde
CHO
H OH
HO H
H OH
HO H
CH2OH
L-Glucose
CHO
HO H
HO H
H OH
HO H
CH2OH
L-Mannose
D- & L- configuration of α-amino acid refers to the configuration of the regardless of the
number of asymmetric carbon in the molecule.
16. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 16
COOH
CH3
NH2H
D-Alanine
COOH
H NH2
CH3
H OH
D-Threonine
1
2
3
4
1
2
3
H
CH3
H2N
COOH
L-Alanine
COOH
H2N H
CH3
H OH
L-Threonine
The D- & L- system has the disadvantage of specifying configuration of only one
stereocenter.
D- & L- configurations are not related to the optical rotation of sugars.
Threo and Erythro system:
A molecule with two adjacent stereocenters and with two groups are common to each carbon
while third group is different i.e. Cabx-Caby gives rise to threo and erythro diastereomers.
When similar groups are on the same side = Erythro
17. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 17
CH3
H Br
CH3
H OH
erythro-3-Bromo-2-butanol
When similar groups are on the opposite side = Threo
CH3
Br H
CH3
H OH
threo-3-Bromo-2-butanol
3-bromo-2-butanol has two asymmetric centres. So, the total number of stereoisomers = 2n
=
22
= 4
NOTE:
The term erythro and threo are generally applied only to those molecules which do not have
symmetric ends. Instead Meso or (d, l) will be used.
18. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 18
CH3
H Br
CH3
H Br
Meso-2, 3-Dibromobutane
Plane of symmetry
CH3
Br H
CH3
H Br
(d,l)-2, 3-Dibromobutane
R-S system:
The Sequence (CIP) Rule is the actual method whereby the four substituents on an
asymmetric carbon may be assigned priorities 1, 2, 3 or 4 so that the absolute configuration R
or S may be determined.
Rule-1: Rank the groups or atoms boned to the asymmetric carbon in order of priority.
Priorities depend on atomic number; the atom of higher atomic number is assigned higher
priority.
If two atoms are isotopes of same element, the atom of higher mass number has the higher
priority.
Rule-2: If the relative priority of two groups can note be determined as above, then look for
next atom, often it may be necessary to proceed atom by atom till a point of difference is
obtained.
19. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 19
Rule-3: In the case of double or triple bond, either atoms or groups are considered as
duplicate or triplicate.
Rule-4: Orient the molecule so that the groups or atoms with lowest priority are directed
away from the observer.
Rule-5: Draw an arrow from the group or atom with highest priority to the group or atom
with next priority (decreasing priority). If you trace a circular path from 1 to 2 to 3 and the
path describes a clockwise rotation, then the center is called R (Latin: rectus means right). If
the path shows a counter clockwise rotation, then the chiral center is called S (L.: sinister
means left).
NOTE:
Case-1: When the group or atom of lowest priority is on continuous solid line, one can look
along C-lowest priority group bond.
20. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 20
H
CH3
I
Br
4
1
2
3
View the molecule
along C-H bond
I
Br
CH3
H
1 2
3
4
R
OR
If the fourth group is on the plane then do double interchange in such a way that the 4th
group
goes below the plane.
H
CH3
I
Br
4
1
2
3
R
I
CH3
H
Br
4
1
2
3
First
interchange
I
Br
H
H3C
4
1
2
3
Second
interchange
Case-2: When the group or atom of lowest priority is oriented towards the observer, one may
rotate the molecule so that priority 4th
group point back.
21. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 21
4
1
2
3
S
4
1
2
3
Rotate
OR
If fourth group is above the plane, then clock wise movement is “S”, while counter clock
wise movement is “R”.
The R & S system of nomenclature can be applied to isomers with more than one asymmetric
carbon. If a compound has more than one asymmetric carbon, the steps followed to determine
whether an asymmetric carbon has R / S configuration must be applied to each of asymmetric
carbon individually.
22. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 22
R-S nomenclature for Fischer projection:
Case-I: If the 4th
group is present on top or bottom of the vertical line in the Fischer
projection.
H
NH2
H3C COOH
1
23
4
S
NH2
H
COOH
1
23
4
R
Case-II: If the 4th
group is present on left or right of the horizontal line in the Fischer
projection.
23. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 23
COOH
NH2
CH3H
1
2
34
S
Ph
C2H5
OHH3C 1
2
3
4
R
Helical descriptors-M & P:
Many chiral molecule lack conventional center that cannot be described by R/S system can be
viewed as helical and may have propeller or screw shaped structure.
To assign descriptor in such molecules highest priority at near group and highest priority at
far group were determined separately.
Sighting down the axis, if moving from near group highest priority to corresponding far
group highest priority requires clock wise rotation then the helix is right handed and is
described as P (Plus). A counter clockwise rotation implies helix is left handed and
designated as M (Minus).
NO2
CH3
O2N CH3
1 2
3
4
P
H
Cl
H3C H
1 2
3
4
M
24. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 24
These M-P convention has relation with R-S configuration as shown in the formula
P = aS M = aR
P = pS M = pR
aS & aR represents Axial chirality
pS & pR represents Stereoplanar chirality
Chirality is also observed in compounds that lack a stereogenic carbon atom.
• Quaternary ammonium salts
R4
N
R3
R1
R2
Cl
R4
N
Cl
R2
R3
R1
25. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 25
• Phosphine oxides
O
P
R3
R1
R2
O
P
R2
R3
R1
• Silicon containing compounds
R4
Si
R3
R1
R2
R4
Si
R2
R3
R1
• Sulfones due to different isotopes
S CH3
O16
O18
H3C
Optical activity in compounds without stereogenic center
The chiral compounds discussed so far contains one or more stereocenter and have their
chirality specified at one or more such centers. There are other chiral compounds without
stereocenter like axial chirality (Stereoaxis), Planar chirality (Stereoplanar) and Helicity.
The central tetrahedron usually occupied by a tetracoordinate atoms e.g. C in Cabcd.
26. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 26
a
bc
d
a
b
d
c
Regular Tetrahedron
If this centre is replaced by a linear grouping such as C-C or C=C=C, the tetrahedral becomes
elongated along the axis. Such elongated tetrahedron (D2d point group with 3C2 axes and 2σ
planes) has lesser symmetry than a regular tetrahedral (Td). Elongate tetrahedron approach
can be applied to a variety of compounds like allenes, spiranes and biphenyls which are chiral
not due to presence of stereocenter but due to stereoaxis.
a
b
c
d
a
b c
d
Elongated Tetrahedron
This extended tetrahedron will be chiral if the pair of ligands or substituent’s at one end of
one axis and the pair at other end are different i.e. the minimum condition for chirality is that
ligand a ≠ b.
Allenes:
Suitable substituted allenes could be chiral was made by Van’t Hoff in 1875 and verified by
Matlan and Mills in 1935.
Allenes contain cumulative double bonds and have general formula
C C C
b
aa
b
C C C
b
aa
b
27. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 27
Simplest allene i.e. propa-1,2-diene is achiral due to presence of two plane of symmetry.
C C C
H
HH
H
Allenes has two types of carbon based on hybridization i.e. two Sp2
hybridized carbon atom
at terminal and one Sp hybridized carbon atom in the middle.
C C C
H
H
H
H
Sp hybridized
Sp2
hybridized Sp2
hybridized
To make allene chiral unlike substituents at either end and also on carbon are added.
C C C
H
H3C
H
CH3 H ≠ CH3
An allene with substituents on one terminal carbon atom are unlike and substituent on other
terminal carbon atoms are same, then it will be achiral due to one symmetry plane.
C C C
H
H3C
H
H
(Achiral)
One plane of
symmetry
28. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 28
Allene with all the four different substituent’s are also chiral.
C C C
H
H3C
Cl
C(CH3)3
(Chiral)
Types of Allenes
(1) Asymmetric allenes: Allenes having asymmetric carbon / C1 point group exhibit
chirality.
C C C
H
C
H
H
(Chiral due to
asymmetric center)
R1
R3
R2
C C C
R2
R1
R3
R4
(Chiral due to
C1 point group)
(2) Dissymmetric allenes: Allenes having C2 point group exhibit chirality.
C C C
H
C
H
R1
R3
R2
C C C
R2
R1
R2
R1
(Chiral due to C2 point group)
C
R3
R1
R2
Conditions for chirality of allenes:
(1) Proper substitution i.e. two different substituents at either end and also on carbon.
(2) Number of double bonds should be even.
29. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 29
The Cumulene with odd number of double bond with terminal carbon atoms having unlike
substituent also will be achiral because both terminal planes will be same.
C C C
R
R'
C
R'
R
Substituent at two ends of cumulated double bonds now lies in the same plane. Hence, they
exhibit geometrical isomerism instead of optical isomerism.
30. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 30
R/S nomenclature for the Allenes:
1. Viewing of molecule from left side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
2. Viewing of molecule from right side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
OR
❖ Always the groups on the solid lines are given priority then priority given to dashed
and wedge lines.
C C C
CH3
H
H
H3C
1
23
4
R
31. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 31
C C C
CH3
H
H
H3C
1
2 3
4
R
Hemispiranes or Alkylidenecycloalkanes:
The replacement of one double bond in an allene by a ring gives alkylidenecycloalkanes
referred to as hemispiranes, does not alter the basic geometry of the allene and exists as
optical form if suitabley substituted.
C C C
CH3
H
H
H3C
For such a system, Optical activity arises if
(1) Number of ring + double bonds should be even.
(2) Proper substitution i.e. two different substituents at either end and also on carbon.
Spiranes:
If both double bonds in the allene system are replaced by rings the resulting molecules are
spiranes. In spirane molecule two rings are perpendicular to each other due to steric crowding
by the hydrogen atoms.
32. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 32
H
H
H
H
H
H
H H
H
H
HH
Spiranes has two types of hydrogen
1. Lateral - 8 hydrogens are lateral
2. Terminal – 4 hydrogens are terminal
H
H
H
H
H H
H H
H H
H H
Terminal Hydrogens
Lateral Hydrogens
Essential criteria for exhibiting optical activity
1. Even number of ring in spiro compound (Odd number of spiro carbon)
2. Proper substitution at only terminal H.
❖ Chirality due to chiral centre can be generated in any spirane compound (even or odd
number of ring) by substitution at lateral hydrogen (Plane of symmetry should not be
there).
33. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 33
R/S nomenclature for the Spiranes:
1. Viewing of molecule from left side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
2. Viewing of molecule from right side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
OR
❖ Always the groups on the solid lines are given priority then priority given to dashed and
wedge lines.
34. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 34
1
2 3
4
S
H
H3C
CH3
H
Biphenyls:
Biphenyls itself is not planar, one benzene ring being slightly twisted in relation to other as a
consequence of steric crowd.
Dihedral angle 45o
Conformation having a 90o
dihedral angle is achiral as a consequence of plane of symmetry.
If each of the phenyl rings of biphenyl has two different ortho / meta substituent, even the
twisted 90o dihedral angle conformer becomes chiral.
In order to interconvert such conformation with their mirror image structure, a rotation
through the higher energy coplanar form must be made. The ease with which this
interconversion occurs will depend on the size of ortho substituents.
Conformational isomers that are isolable due to high energy barrier are called atropisomers (a
= not, tropos = turn).
The name was introduced by Kuhn i 1933, but atropisomerism was first detected in 6, 6’-
dinitro-2, 2’-diphenic acid by Cristie in 1922.
The C-C sigma bond is known as pivotal bond.
Biphenyls are classified into two categories
1. Bridged biaryls
35. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 35
C
H2 n
n > 2, leads to atropisomersim irrespective of bulkiness of two ortho
substituents
2. Non bridged biaryls
R
R'
R
R'
Conditions for biphenyls to be enantiomeric or resolvable:
1. Two aryl ring must be non planar. This can be done by introducing bulky group in
ortho position.
2. Most tetra substituted biphenyls can be resolved and quite stable to racemisation.
Buttressing effect (BE-effect):
The substituent in meta position tend to enhance the racemisation barrier i.e. preventing the
outward bending of an ortho substituent, which could otherwise occur in the transition state
for racemisation.
In simple the extra meta-group prevents that the ortho-group can bend and therefore makes
the transition state higher in energy. (The meta group ‘buttresses’ or ‘reinforces’ the bond of
the ortho-substituent). This is known as buttressing effect.
36. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 36
The rate of racemisation of the 3-nitro derivative is much lower compared to 5’-nitro
derivative. The meta substituent increases the effective size of the ortho substituent.
MeO
H
NO2
COOH
MeO
H
NO2
COOH
NO2
NO2
NO2 gp in meta increase effective
size of ortho OMe hence
racemization rate decreases
NO2 gp in meta does not have
much influence on ortho H
hence racemization rate is more
R/S nomenclature for the Biphenyls:
1. Viewing of molecule from left side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
H3C NO2
NO2
CH3
1
2
34
S
H3C
O2N
NO2
CH3
37. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 37
2. Viewing of molecule from right side
(a) Groups near to the observer are drawn on the bold line and away groups are on the
thin line.
(b) Priority will be given to near group according to CIP rule than far group.
OR
❖ Always the groups on the solid lines are given priority then priority given to dashed and
wedge lines.
1
2
3
4
H3C
O2N
NO2
CH3
S
H3C
O2N
NO2
CH3
NO2
CH3
1 2
3
4
S
O2N CH3
38. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 38
Classification of cyclic compounds
Cyclic compounds are classified, according to the number of atoms in the ring and properties,
as small rings with 3 or 4 atoms, common rings with 5–7, medium rings 8–11, and large rings
with 12 or more.
Types of strain
Conformational analysis of simple alkanes revealed two types of strain—torsional and steric.
According to Hendrickson and separately Allingerthe total strain of a conformation is the
sum of:
Bond strain - stretching or compression of chemical bonds. This type of strain is rather
severe and is not encountered very often in organic compounds. To minimize bond strain, a
molecule adopts conformations that have other, less energy-demanding, types of strain.
Torsional strain (eclipsing strain, Pfitzer strain) is caused by eclipsing interactions.
Torsional strain is considerably higher compared to steric or angle strain, which are explained
next.
Steric strain (Van der Waals strain, Prelog strain) is caused by atoms forced too close to
each other. Transannular strain (Prelog strain) is a form of steric strain characteristic of
medium rings.
Angle strain (Bayer strain, classical strain) is a result of deviation from the ideal bond
angle. Compared to other types of strain, increase in energy of a conformation caused by
angle strain is relatively low. As a result, a molecule can accommodate relatively large
deviation from an ideal bond angle and still be stable.
Van’t Hoff and Lebel proposed tetrahedral geometry of carbon. The bond angel is of 109˚ 28'
(or 109.5˚) for carbon atom in tetrahedral geometry (methane molecule). Baeyer observed
different bond angles for different cycloalkanes and also observed some different properties
and stability.
On this basis, he proposed angle strain theory.
The theory explains reactivity and stability of cycloalkanes.
Baeyer proposed that the optimum overlap of atomic orbitals is achieved for bond angel of
109.5o. In short, it is ideal bond angle for alkane compounds. Effective and optimum overlap
39. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 39
of atomic orbitals produces maximum bond strength and stable molecule. If bond angles
deviate from the ideal then ring produce strain. Higher the strain higher will be instability.
Higher strain produce increased reactivity and increases heat of combustion.
Baeyer proposed “any deviation of bond angle from ideal bond angle value (109.5o) will
produce a strain in molecule. Higher the deviation lesser will be instability.
Baeyer’s theory is based upon some assumptions as following.
1. All ring systems are planar. Deviation from normal tetrahedral angles results in to
instable cycloalkanes.
2. The large ring systems involve negative strain hence do not exists.
3. The bond angles in cyclohexane and higher cycloalkanes (cycloheptane,
cyclooctane, cyclononane……..) are not larger than 109.5o because the carbon
rings of those compounds are not planar (flat) but they are puckered (Wrinkled).
According to Baeyer, the relative order of stability for some common cycloalkanes is as
under.
Cyclopentane > Cyclohexane >Cyclobutane> Cyclopropane
Actual observed order of stability for these cycloalkanes is as under.
Cyclohexane > Cyclopentane >Cyclobutane> Cyclopropane
According to Baeyer, the bond angle in cyclopentane is 108˚ (the geometry is
pentagonal) that is very close to tetrahedral angle (109.5˚), so it is almost free from ring
strain.
Heat of Combustion and Relative Stability of Cycloalkanes
The amount of heat evolved when one mole of compound is burned in carbon
dioxide and water is referred as heat of combustion.
Heat of combustion is important property to know the stability and other valuable
information. The information from heat of combustion is important to understand the
Baeyer’s theory and its limitations.
41. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 41
Successfulness of Baeyer’s angle strain theory
• Baeyer rightly proposed that cyclopropane and cyclobutaneare flat molecule and
having angle of 60˚ and 90˚ those are much deviated from the ideal tetrahedral
value of 109.5˚ hence these ring systems are unstable and easily undergo ring
opening reactions. There is much angle strain in cyclopropane and cyclobutane.
• Baeyer also proposed that cyclopentane is not need to be planar but it is planar as in
that condition the angle is much near to ideal tetrahedral angle
Unsuccessfulness of Baeyer’s angle strain theory
• Baeyer was not able to explain the effect of angle strain in larger ring systems.
• According to Baeyer cyclopentane should be much stable than cyclohexane but
practically it is reversed.
• Larger ring systems are not possible according to Baeyer as they have negative
strain but they exist and much stable.
• Larger ring systems are not planar but puckered to eliminate angle strain.
Coulson-Moffitt Model or Concept of Maximum Overlap of Carbon
Orbitals (Bent bond/Banana bond Theory)
• A bent bond, also known as a banana bond, is a type of covalent chemical bond with
geometry somewhat indicative of a banana.
• The term itself is a general representation of electron density or configuration
resembling a similar "bent" structure within small ring molecules, such as
cyclopropane (C3H6) or as a representation of double or triple bonds within a
compound that is an alternative to the sigma and pi bond model.
42. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 42
Sachse-Mohr Theory (Theory of Strainless Rings)
Sachse Mohr’s theory proposed that higher member ring can become free from strain if all
the ring carbons are not forced into one plane. They exhibit in two non-planar ‘folded’ or
‘puckered’ conformations both of which are completely free from strain. These are
strainless as the carbon atoms lie in different planes and the normal valency angle (109.5o
)
is retained. These are called the ‘Chair’ Form or the ‘Z’ Form and the ‘Boat’ Form or the
‘C’ Form because of their shapes.
The chair conformation is the most stable conformation of cyclohexane.
Conformational analysis
The various arrangements in space that is available for a molecule by rotation about single
bond its conformation. There are in principle an infinite number of conformations, but a
molecule will adopt a geometry that minimises total energy; this minimum energy is given by
Esteric = E(r) + E(q) + E(f) + E(d))
Where, E(r) = stretching energy, E(q) = strain energy, E(f) = torsion energy, E(d) = non-
bonding interactions.
The investigation of various conformations of a molecule and their stabilities is known as
conformational analysis.
43. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 43
Understanding the differences in energy with conformational analysis allows prediction of
relative rates of compounds.
Conformation of Cyclopropane:
In cyclopropane, the three carbon atoms lie in a plane. All C-C bond lengths are same and
three carbons form an equilateral triangle. The hybridization at each carbon atom is Sp3
.
The bonding electrons principally lie outside the triangular internuclear line resulting in bent
bonds. There are three strained bonds and six eclipsed hydrogens.
Newmann projection of cyclopropane.
44. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 44
Conformation of Cyclobutane:
Cyclobutane has internuclear angle of 90o. There are four strained bonds and eight eclipsed
hydrogens.
Cyclobutane is not planar but puckered i.e. one –CH2- group bent at an angle of about 25o
.
The molecule flips from one puckered conformation to other.
Due to bent at angle of about 25o
from plane of three ring carbons there will be reduction in
the eclipsed hydrogen interaction and compensate for the increase in bond angle strain.
45. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 45
Conformation of Cyclopentane:
If the structure of cyclopentane is planar, the C-C-C bond angle will be 108o
which is so close
to normal tetrahedral bond angle of 109o
.28’ that is no significant strain effect would be
expected.
However, in such structure all of the hydrogens are completely eclipsed and it would have
considerable torsion strain resulting from ten H---H eclipsing interactions.
Torsional strain is reduced by moving one or two carbon away from the plane. This
results in an increase in angular strain. Carbon atoms move in and out of the plane
rapidly, resulting in an illusion of rotation of the molecule. This phenomenon is termed
as pseudo-rotation. The actual structure is of open envelope shape. In which four carbon
atoms lie in plane and one above or below it.
46. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 46
Conformation of Cyclohexane:
A planar structure of cyclohexane is clearly improbable. The bond angle would be 120o
i.e.
10.5o
larger than the ideal tetrahedral angle. Also every C-C bond in such structure would be
eclipsed. The resulting angle and eclipsing strain would severely destabilize this structure.
Planar
Erel = Very large
If two carbon atoms on opposite side of six member ring are lifted out of the plane, much of
the angle strain can be eliminated. It can form Chair conformation or Boat conformation.
In 1950, interconversion of chair conformation and the different orientation bond was
elucidated by D. H. R. Barton.
Chair conformation:
It is non planar puckered conformation. All bonds are fully staggered therefore Pitzer strain is
minimized. The bond angles are not exactly 109o
.28’ but 111o
. Relative energy is zero (four
carbons are planar, one puckered up and one puckered down)
Cyclohexane forms a number of different conformers. However, structure other than
the chair conformation suffers torsional strain, angular strain or both.
Boat Conformation:
Even though boat conformation is free from angular strain. However, in addition to the
torsional strain resulting from 4 H---H eclipsing interactions, it also has a flagpole interaction
between the hydrogen atoms on 1- and 4-carbon atoms. Hence, it has higher energy than
chair conformation of about 25 KJ/mol or 6.0 Kcal/mol.
47. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 47
The eclipsing interaction can be relieved by slightly twisting two C-C bonds resulting in new
conformation called twist boat conformation.
In boat conformation there are four types of hydrogens
1. Flag pole hydrogen – 2 Nos (Hfp)
2. Bow spirit hydrogen – 2 Nos (Hbs)
3. Quasi axial hydrogen – 4 Nos (Hqa)
4. Quasi equatorial hydrogen – 4 Nos (Hqe)
Hfp
Hbs
Hqa
Hqe
Hqa
Hfp
Hbs
Hqe
Twist Conformation:
It is more stable than the boat conformation, but less stable than
than chair conformation. The flagpole interactions and torsional strain in the boat
conformation are reduced in the twist conformer.
The twist boat has energy of about 21 KJ/mol or 5.5 Kcal/mol which is lower than boat
conformer.
Half chair conformation:
It is a transition state conformation. The half chair conformer lies about 43 KJ/mol or 10
Kcal/mol above chair conformation. It has five carbons lie in plane and one puckered out of
plane.
48. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 48
Stability order of cyclohexane conformers:
Chair > Twist boat > Boat > Half chair
On careful examination of cyclohexane we find that the twelve hydrogens are not structurally
equivalent.
Equatorial Bonds: These are three sets of two parallel bonds, each of which are
parallel to two of the bonds in the ring. Equatorial bonds alternate from slightly up to
slightly down orientation on moving from one carbon to the next.
49. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 49
Axial Bonds: They are parallel to each other and to the principal axis, but
perpendicular to the average plane of the ring. There are three bonds facing up and
three facing down.
An inversion of a cyclohexane chair involves all of the conformations of cyclohexane.
Starting with a chair conformation a, cyclohexane first passes through a “half-chair”
conformation b. The half-chair, as expected, has a very high energy and is only a transition
state, which gives rise to the actual conformation—twist-boat c. Next, the twist-boat
conformation flips into the alternative twist-boat conformation e. The transition state for this
flip is the boat conformation d. Then, the cyclohexane molecule passes through another half-
chair transition state f (mirror image of the first one) and finally arrives at the alternative
chair conformation g. At room temperature cyclohexane interconvert from one chair form to
another referred to as ring inversion or ring flipping.
Axial and equatorial bonds also undergo interconversion, when a chair conformation flips to
the other. However, their relative orientations in space do not change.
50. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 50
Since two equilibrium chairs are in rapid equilibrium all twelve hydrogen have 50%
equatorial and 50% axial character.
Conformations of substituted cyclohexanes:
Monosubstituted cyclohexanes:
The axial and equatorial positions have different spatial orientations. In chair-chair
interconversion, substituent’s moves from equatorial to axial and vice versa. Bigger
substituent’s has more steric interaction in an axial position than in equatorial. Hence, the
chair conformation which has the larger group on equatorial is more stable.
Y
H
H
H Y
H
H
H
Steric repulsion
Y = axialY = equitorial
When larger group occupies the axial position there is a steric repulsion between the
substituent and the axial hydrogens which are three carbons away. These repulsive effects are
called 1, 3 –diaxial interactions. It destabilizes the axial conformer about 1.8 Kcal/mol
compared to equatorial conformer.
1, 3 –diaxial interactions is approximately equivalent to one gauche butane interaction of 0.9
Kcal/mol. Since in axial methyl cyclohexane two gauche butane type of interaction between
axial methyl and two ring C-C bond destabilizes the axial conformer while such interactions
does not exists when methyl group is in equatorial.
51. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 51
Due to difference in energy between placing a substituent in the axial vs equatorial position,
the two chair conformers are no longer equal energy.
With methyl substituent a hydrogen a hydrogen is directed towards 1, 3 – hydrogens. As the
substituent becomes larger, steric interaction with 1, 3-hydrogen increases.
With ethyl substituent, if the extra methyl is pointed towards 1, 3-hydrogens can rotate to
move away. Has energy similar to methyl cyclohexane i.e. 1.8 Kcal/mol.
H
H
C
H
H
H
View from this side
View from this side
C
H
H
H
52. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 52
H
H
C
H3C
H
H
H
H
C
H
H
CH3
With isopropyl substituent, can still have a conformer with hydrogen pointed towards 1, 3-
hydrogens. Has energy of about 2.1 Kcal/mol.
H
H
C
H3C
H
CH3
H
H
C
H
CH3
CH3
With tertiary butyl group must have methyl group towards 1, 3-hydrogens. Its energy is
greater than 4.5 Kcal/mol.
H
H
C
H3C
CH3
CH3
The relative population of the two chair conformers can be calculated by the equation,
The free-energy difference between conformers is referred to as the conformational free
energy. For substituted cyclohexanes it is conventional to specify the value of -Gc for the
equilibrium:
[Axial][Equatorial]
53. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 53
As - Gc is negative when the equatorial conformation is more stable than the axial, the value
of - Gc is positive for groups that favor the equatorial position. The larger the - Gc, the greater
the preference for the equatorial position.
The equatorial conformer of ethyl cyclohexane is 7.4 KJ/mol more stable than the axial
conformer. Calculate the percentage of ethyl cyclohexane which is in equatorial at 25o
C.
∆G = -RT ln Keq
Keq = e-∆G/RT
= e-7.4 / 0.0083 x 298
=e-2.99
Keq = 0.0504
54. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 54
Disubstituted Cyclohexanes and Diastereoisomerism:
In a disubstituted cyclohexane, the most stable conformation is the one in which the largest
number of substituents are in equatorial positions. If the number of equatorial and axial
substituents of the same size in two conformations is the same, then the two conformations
are equally stable.
1, 1 -Disubstituted cyc1ohexanes:
The two identical groups, like in 1, 1-dimethylcyc1ohexane, occupy an equatorial and an
axial position in both conformations. Hence, both are equally stable and so identical.
When two different substituents are present, the bulkier one preferentially occupies the
equatorial position. Example is 1-methyl-1-cyc1ohexanol. The conformation with the larger
methyl group in the equatorial position is more stable, so the two conformers are present in
unequal amounts. Because the substiiuents are present in different positions, the two
conformations are diastereomers. However, since they interconvert very fast, they cannot be
separated.
1,2-, 1,3- and 1,4-disubstituted cyclohexanes exhibit cis–trans isomerism. In
a cis isomer, both substituents are on the same side of the ring, while in a trans isomer the
two substituents are on the opposite sides. Cis–trans isomerism is a consequence of restricted
rotation about carbon–carbon bonds in cyclic compounds. Note that in a cis isomer both
substituents point “up” (or “down”) and that in a trans isomer one substituent points “up” and
the other one “down”. The chair flip does not change the orientation of substituents. One that
was pointing “up” still points “up” and the one that was pointing “down” still points “down”.
55. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 55
Substitution Pattern and Cis/Trans Isomerism
Substitution Position Isomer
1, 2- and 1, 4-
disubstituted
e, e & a, a trans
e, a & a, e cis
1, 3-disubstituted
e, e & a, a cis
e, a & a, e trans
1, 2- disubstituted
CH3
CH3
CH3
CH3
H H
H
H
(e, e) (a, a)
No axial methyl but
one gauche butane
interaction between
to methyl groups
Two axial methyl
i.e. two 1,3-diaxial
interaction
Erel = 0.9 Kcal/mol Erel = 2 x 1.8 = 3.6 Kcal/mol
56. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 56
1, 4- disubstituted
1, 3-disubstituted
Two substitutions by bulky groups, ring distortion takes place. In the chair conformation of
1,4-di-t-butylcyclohexane the bulky t-butyl groups even in diequatorial positions cannot
avoid steric interactions with the adjacent hydrogens. Hence, the molecule prefers to pucker
into a twist boat form so that these groups are away from all the adjacent hydrogens. In the
twist boat form, the groups are not exactly equatorial as in the chair conformation, but are
directed away from the ring and are known as the pseudoequatorial positions.
Another factor which predominates in deciding the stability of the conformations is the
intramoleculer H-bonding e.g. in the 1, 3- and 1, 4- dihydroxy cyclohexanes. The diaxial
chair contormation of cis-l, 3-dihydroxycyclohexane is preferred due to stabilization by
intramolecular H-bonding, as the two hydroxy groups are closer, while this is not possible in
the diequatorial form.
57. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 57
More interesting is the example of cis-l, 4-dihydroxycyclohexane where the unfavourable
boat form is the preferred conformation due to intramolecular H-bonding and the molecule
exists in only one form.
Conformational effect on reactivity:
In cyclic system to satisfy a particular mechanism a suitable conformation may be of higher
energy is adopted.
Substitution reactions:
SN1: Acetolysis of cis-4-t-butylcyclohexyltosylate. Axial conformer reacts faster due to
relieve in the steric strain due to 1,3-diaxial interaction and forms carbocation very easily.
58. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 58
OTs
OTs
Fast
Slow
SN2 reaction: Axial conformer reacts faster due to relieve in the steric strain due to 1,3-
diaxial interaction and leads to more stable (e, e) conformation with two bulky in equatorial
position. Displacement equatorial X group by PhS-
leads to the formation of less stable (e, a)
conformation.
X
X
PhSNa
PhSNa
SPh
PhS
SPh
Less stable product
PhS
Saponification of an ester: If the ester is in the axial position or in a equatorial position what
is the rate. The equatorial acetate will be hydrolysed faster as compared to the axial ester.
Reaction of axial ester decelerated due to severe developing 1,3-diaxial interactions in
transition state.
59. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 59
COOEt
OEt
OH-
O
NaOH
COOH
OEt
OH-
O
NaOH
COOEt
H
H
COOH
Alcohol oxidation: Destabilizing 1,3-diaxial interactions in cis chromate ester accelerated its
break down to the ketone.
60. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 60
E2 elimination reaction: occurs through anti periplanar transition state. In cyclic
compounds, two leaving groups must be diaxial so as to assume anti periplanar arrangement.
1-Chloro-2methylcyclohexane undergoes elimination reaction in presence of base to give 3-
methylcyclohexene and 2-methylcyclohexene is not all formed.
CH3
Cl
CH3 CH3
Base
Only prodct formed
1-Chloro-2methylcyclohexane undergoes elimination reaction to give 3-methylcyclohexene
through less stable conformer. Since less stable conformer has two groups in diaxial position
i.e. one axial hydrogen and one axial chloro group and hence it assume anti periplanar
arrangement must for elimination reaction.
2-methylcyclohexene is not formed at all because the hydrogen is in equatorial position and
anti periplanar arrangement is not possible.
CH3
Cl
Cl
CH3
H3C
Cl
H
H
More stable
conformer
Less stable
conformer
Base
Axial
Axial
:B
H3CCH3
CH3
61. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 61
Pyrolytic elimination (Syn):
Pyrolytic elimination reaction of acetate, benzoate and xanthates take place through cyclic six
membered transition states which require cis rearrangement.
(1S, 2R)-Ethyl-2-acetoxycyclohexanecarboxylate undergoes syn elimination reaction through
cyclic six membered transition state to give ethylcyclohex-2-enecarboxylate.
OCOCH3
COOEt
COOEt
H
OCOCH3
H
H
COOEt
H
O
H
H
O
CH3
COOEt
H
-CH3COOH
6-membered cyclic TS
(e, a) Cis to each other
(1S,2R)-ethyl 2-
acetoxycyclohe
xanecarboxylate
ethyl cyclohex-2-enecarboxylate
Conformation of Cycloheptane:
Cycloheptane is the largest common ring and it exhibits some features associated with
medium rings such as a more difficult preparation and steric strain in some conformations.
Hendrickson in 1961 distringusihed two general type of conformation of cycloheptane-chair
and boat.
Chair Boat
62. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 62
Both chair and boat of cycloheptane exhibit torsional strain are quite flexible that easily
undergo pseudorotation to lower energy conformations twist char and twist boat. The
interconversion barrier between the chair and boat is computed to be 8 Kcal/mol.
The lowest energy conformation is a twist-chair, while a twist-boat has slightly higher energy
due to the presence of the intraannular “flagpole” hydrogen
63. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 63
Earlier part of stereochemistry was concentrated on the stereo center.
Now we start to see the relationship between the ligands attached to stereo center if the
attached ligands are homomorphic in nature.
Homomorphic Groups / Ligands / Atoms:
The Groups / ligands / atoms which are in isolation look the same or super imposable mirror
images of each other are called homomorphic groups / ligands / atoms.
Homo in greek means same
Morph in greek means form
In case of atoms, they must be of same element example two H’s or two Br atoms. If we
isolate the two H’s, then they are same and super imposable to each other hence they are
called homomorphic hydrogen's.
C
X
Y
A B
Stereo center
*
C
X
Y
A B
Relation
between
X & Y
C
CH3
CH3
H H Homomorphic
groups
Homomorphic atoms
64. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 64
In case of groups, they must have same constitution and configuration. For example two
methyl or two Ph groups of same chirality R or S. They are called homomorphic groups /
ligands / atoms.
TOPICITY: (TOPOs in Greek means place) can be defined as geometrical or
sterochemical relationship between homorphic groups / ligands / atoms and structure of the
molecule.
Different types of relationships are possible for homorphic ligands / groups / atoms.
1. Homo topic (Homo-same; topo-place)
2. Hetero topic (Hetero-different; topo-place)
Ligands can not by itself be called homotopic or heterotopic, in order to use this
terminologies a comparison with other homomorphic ligand or ligands present either in the
same molecule (internal comparison) or in a different molecule (external comparison) is
necessary.
Two criteria are used to decide whether the ligands / groups are equivalent or not
1. Substitution-addition criteria
2. Symmetry criteria
Are employed to determine the topic relationship of homomorphic ligands
C
CH3
CH3
HH
H H
Isolated Isolated
Identical and super imposable
65. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 65
(a) Homo topic ligands:
Two or more ligands that are identical when viewed in isolation but individual replacement of
two identical ligands by another give rise to identical molecule, then they are called
homotopic ligands.
1. Substitution-addition criteria
Two homomorphic ligands are homotopic if substitution (replacement) of first one and other
by different test ligand leads to homomers or identical product.
Example-1:
Example-2:
Ha X
Hb X
Identical product
C C C
Hb
HaH
H
C C C
H
XH
H
C C C
X
HH
H
66. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 66
Example-3:
Example-4:
Ha F
Hb F
Identical
products
COOH
Hc
Ha Hb
Hc F
COOH
H
F H
COOH
H
H F
COOH
F
H H
Ha D
Identical
products
COOH
Ha OH
Hb D
COOH
D OH
COOH
H OH
HbHO
COOH
HO D
COOH
HO H
COOH
67. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 67
(b) Homo topic faces
Two faces of a pi system or a double bond are homotopic if addition to either face gives same
or identical product.
Example-1:
Example-2:
68. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 68
2. Symmetry criteria
(a) Homo topic ligands
Two homomorphic ligands are homotopic if they can interchange position by rotation around
Cn axis.
Example-1:
Example-2:
69. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 69
(b) Homo topic faces
Two faces of pi system are homotopic if they can interchange face result in same structure by
rotation around C2 axis.
Example-1:
Example-2:
70. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 70
NMR Spectroscopy of Homotopic Hydrogen
If the hydrogen atoms in the molecule are homotopic, then they are chemically equivalent.
Hence they will resonate at same chemical shift values.
SUMMARY
Between homotopic groups and faces no differentiation is possible either by enzyme or by
NMR or by human being because they are homomers or identical.
Topicity
Substitution-
addition criteria
Symmetry criteria Reactivity
Homotopic
groups and
faces
Homomers /
Identical
Cn or C2
No differentiation
possible
71. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 71
Hetero topic ligands
Two or more ligands that are identical when viewed in isolation but individual replacement of
two identical ligands by another ligand give rise to two structurally different (isomeric)
molecules, then they are called heterotopic ligands.
Constitutionally Hetero topic ligands
Two or more ligands in a molecule that are identical on individual replacement by another
ligand give rise to two molecule that constitutional isomers of each other, then the original
two ligands are said to be constitutionally heterotopic ligands.
72. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 72
Example-1:
Example-2:
C C
H3C
H
CH3
COOH
C C
X
H
CH3
COOH
C C
H3C
H
X
COOH
CH3 X CH3 X
1
23
1
23
H F H F
NO2
H
H
NO2
F
H
NO2
H
F
73. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 73
C CC
(R)(S)
H
Cl
Ha
Hb
Ha Cl Hb Cl
C CC
H
Cl
Cl
H
CC C
H
Cl
Cl
H
1
23
41
23
4
They are enantiomersand hence enantiotopicligands
Stereo chemically heterotopic
Two or more ligands in a molecule that are identical on individual replacement by another
ligand give rise to two molecule that are enantiomers / super imposable mirror images of each
other, then the original two ligands are said to be enantiotopic ligands.
(a) Enantiotopic ligands
1. Substitution-addition criteria
Two homomorphic ligands are enantiotopic if substitution (replacement) of first one and
other by different test ligand leads to enantiomers.
Example-1:
Example-2:
74. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 74
Example-3:
Example-4:
(R) (S)
OH
O
Hb Ha
Ha D Hb D
OH
O
H D
OH
O
D H
They are enantiomersand hence Ha & Hb are enantiotopic ligands
(R)(S)
Ha D Hb D
H3C
CH3
Ha
H
Hb
H
H3C
CH3
D
H
H
H
H3C
CH3
H
H
D
H
They are enantiomersand hence Ha & Hb are enantiotopic ligands
75. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 75
(b) Enantiotopic faces
Two faces of a pi system or a double bond are enantiotopic if addition to either face gives
enantiomeric product.
Example-1:
Example-2:
(R) (S)
O
H
Ph
Top face
Bottom face
H
Ph
Et
OH
H
Ph
OH
Et
EtMgBr EtMgBr
Addition reaction
from either face leads
to formation of
enantiomers and
hence two faces are
enantiotopic
O
H
Ph
Top face
Bottom face
H
Ph
H
Ph
OH
CN
CN
OHHCN
HCN
(S)
(R)
Addition reaction from either face leads to formation of
enantiomers and hence two faces are enantiotopic
76. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 76
Molecules having stereo heterotopic ligands (enantiotopic) exhibit prostereoisomerism or
prochirality
Prostereoisomerism or Prochirality
Prochiral molecules are those which are achiral can be converted into chiral molecule in a
single step.
Prochirality may be the result of substitution reaction of Sp3 carbon substituent (usually
hydrogen) with other substituent results in chiral center.
OR
Prochirality may be the result of addition reaction of a Sp2 carbon to a chiral Sp3 carbon
with nucleophile.
Prochirality may be the result of substitution reaction of Sp3
hybridized
carbon substituent.
(R) (S)
Ha Cl Hb Cl
12
3
1
2
3
4
C
CH3
Hb
Ha
4
C
CH3
H
Cl
C
CH3
Cl
H
4th group on wedge bond hence
clock wise "S" configuration
PROCHIRAL
CHIRAL CHIRAL
PROCHIRAL
HYDROGENS
77. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 77
Prochirality may be the result of addition reaction of Sp2
hybridized
carbon.
2. Symmetry criteria
(a) Enantiotopic ligands
Two homomorphic ligands are enantiotopic if they can interchangeable through plane of
symmetry or center of inversion or Sn axis.
Example-1: Molecule with plane of symmetry (σ) containing homomorphic ligand is
enantiotopic.
(R)(S)
NaBH4
1
2
3
1
2
3
4
CH2H3C
C
H3C
4
View the molecule through C-H bond for assigning the
configuration
PROCHIRAL
CHIRAL CHIRAL
O
C
H
OH
H3C
C
H2
C
OH
H
H3C
C
H2
H3C H3C
NaBH4
COOH
Ha OH
Hb OH
COOH
plane of symmetry
78. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 78
Example-2: Molecule with Improper axis of symmetry (Sn) containing homomorphic
ligand is enantiotopic.
Example-3: Molecule with Center of inversion (i) containing homomorphic ligand
enantiotopic.
(b) Enantiotopic faces:
Two faces are enantiotopic if they can interchangeable through plane of symmetry or center
of inversion or Sn axis.
O
H
Ph
Top face
Bottom face
O
Ph
H
Top face
Bottom face
Structure is not same upon rotation hence mirror plane
exists.
H3C OH
Ha
Hb
Rotation Reflection
HO CH3
Hb
Ha
H3C OH
Hb
Ha
Cl
Cl
OH
OH
Inversion center
79. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 79
NMR Spectroscopy of Enantiotopic Hydrogen
If the hydrogen atoms in the molecule are enantiotopic, then they are chemically equivalent.
Hence they will resonate at same chemical shift values.
SUMMARY
Between enantiotopic groups and faces differentiation is possible either by enzyme or by
NMR in chiral reagent or catalyst.
Topicity
Substitution-
addition criteria
Symmetry
criteria
Reactivity
Enantiotopic
groups and
faces
Enantiomers σh or Sn
Differentiation
possible
O
Ph
H
Top face
Bottom face
Molecularmirrorplaneexists
80. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 80
(a) Diastereotopic ligands
Two or more ligands in a molecule that are identical on individual replacement by another
ligand give rise to two molecule that are diastereomers / non super imposable not mirror
images of each other, then the original two ligands are said to be diastereotopic ligands.
Substitution-addition criteria
Two homomorphic ligands are diastereotopic if substitution (replacement) of first one and
other by different test ligand not already attached to the molecule leads to diastereomers / non
super imposable not mirror images.
Example-1:
Substitution of Ha & Hb by Cl leads to formation of trans
and cis products which are diastereomers and hence two
hydrogens are diastereotopic
H3C
C C
H
Hb
Ha
H3C
C C
H
H
Cl
H3C
C C
H
Cl
H
Ha
Cl
Hb
Cl
-CH3 & -Cl
are
Cis
-CH3 & -Cl
are
Trans
81. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 81
Example-2:
Geminal methylene protons adjacent to a stereocenter on substitution test
by other ligands not already present in the molecule usually leads to
diastereomers and are usually diastereotopic.
Ha
Cl
Hb
Cl
-Br & -Cl
are
Trans
-Br & -Cl
are
Cis
Br
H
Ha
Hb
Br
H
Cl
H
Br
H
H
Cl
Substitution of Ha & Hb by Cl leads to formation of trans
and cis products which are diastereomers and hence two
hydrogens are diastereotopic
O
Hb Ha
Stereo center
Adjacent to a stereo
center hence they are
usually diastereotopic
82. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 82
RR SS
RS SR
Enantiomers
Enantiomers
Diastereomers
Diastereomers
Diastereomers
Example-1:
Example-2:
Ha
Cl
Hb
Cl
O
Hb Ha
O
Cl H
O
H Cl
(S)
(R) (R)
(R)
Substitution of Ha
& Hb by Cl leads to
formation of
diastereomers and
hence two
hydrogens are
diastereotopic
Ha
D
Hb
D
(S)
(R) (R)
(R)
CH3
H Cl
Hb Ha
Cl
CH3
H Cl
D H
Cl
CH3
H Cl
H D
Cl
(R)
Substitution of Ha
& Hb by D leads to
formation of
diastereomers and
hence two
hydrogens are
diastereotopic
83. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 83
(b) Diastereotopic faces
Two faces of a carbonyl group adjacent to a stereo center upon addition reaction leads to
diastereomers and possess diastereotopic face.
NMR Spectroscopy of Diastereotopic Hydrogen
If the hydrogen atoms in the molecule are diastereotopic, then they are chemically and
magnetically non equivalent. Hence they will resonate at different chemical shift values.
Stereo center
CH3
O
H3C H
C6H5
Two faces of a
carbonyl group
adjacentto a stereo
center
H
H
HO
H
CH3
Diastereotopic hydrogens
Due to non equivalentnatureof protons
it splits into multiplet.
84. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 84
SUMMARY
Between diastereotopic groups and faces differentiation is possible either by enzyme or by
reagent or by NMR.
Topicity
Substitution-
addition criteria
Symmetry
criteria
Reactivity
Diastereotopic
groups and
faces
Diastereomers Not applicable
Differentiation
possible
EXAMPLES FOR HOMOTOPIC, ENANTIOTOPIC AND
DIASTEREOTOPIC LIGANDS
H
Br
Ha
Hb
H
Br
D
H
H
Br
H
D
trans
Cis
Substitution of Ha &
Hb by D leads to
formation of
diastereomers and
hence two hydrogens
arediastereotopic.
85. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 85
Ha
Hb
D
H
H
D
Substitution of Ha & Hb by D
leads to formation of
homomers and hence two
hydrogensarehomotopic.
MeO OMe
H H
MeO OMe
D H
MeO OMe
H D
Substitution of H & H by D
leads to formation of
homomers and hence two
hydrogensarehomotopic.
Substitution of H & H by D
leads to formation of
homomers and hence two
hydrogensarehomotopic.
Cl Cl
H H
Cl Cl
D H
Cl Cl
H D
R R
R R
R R
86. Stereochemistry
Dr. Krishnaswamy. G, DOS & R in Organic Chemistry, TUT Page 86
O O
H
Ph CH3
H3C Ph
H
O O
H
Ph CH3
H3C Ph
H
C2
H & H are
interchangeable by C2
rotation and hence two
hydrogens are homotopic.
H
H
D
H
H
D
Substitution of H & H by D
leads to formation of homomers
and hence two hydrogens are
homotopic.
H
H
D
H
H
D
Substitution of H & H by D
leads to formation of
enantiomers and hence two
hydrogensareenantiotopic.
H
H
D
H
H
D
Substitution of H & H by D
leads to formation of
diastereomers and hence two
hydrogens are diastereotopic.