scoresvideos
Organic Chemistry
Table of Contents
Unit 5 Overview: Stereochemistry at Tetrahedral Centers
5.1 Enantiomers and the Tetrahedral Carbon
5.2 The Reason for Handedness in Molecules: Chirality
5.3 Optical Activity
5.4 Pasteur’s Discovery of Enantiomers
5.5 Sequence Rules for Specifying Configuration
5.6 Diastereomers
5.7 Meso Compounds
5.8 Racemic Mixtures and the Resolution of Enantiomers
5.9 A Review of Isomerism
5.10 Chirality at Nitrogen, Phosphorus, and Sulfur
5.11 Prochirality
5.12 Chirality in Nature and Chiral Environments

🥼organic chemistry review

5.5 Sequence Rules for Specifying Configuration

Citation:

Chiral molecules have unique 3D structures that determine their properties and reactions. Understanding how to specify their configuration is crucial for predicting behavior and synthesizing specific isomers.

The Cahn-Ingold-Prelog rules provide a systematic way to assign R or S labels to chiral centers. This allows chemists to communicate and work with precise molecular structures in organic synthesis and analysis.

Specifying Configuration in Chiral Molecules

Cahn-Ingold-Prelog sequence rules

  • Prioritize substituents around a chiral center using Cahn-Ingold-Prelog (CIP) sequence rules enables determination of absolute configuration (R or S)
  • Rank substituents by atomic number highest atomic number receives highest priority (bromine > chlorine)
  • Compare the next set of atoms if substituents have the same atomic number continue moving outward until a point of difference is found (ethyl > methyl)
  • Consider double or triple bonds as an equivalent number of single-bonded atoms a double bond is treated as two single-bonded atoms a triple bond is treated as three single-bonded atoms ($\text{C}=\text{O}$ > $\text{C}-\text{OH}$)
  • Assign priority based on the number of atoms for substituents with the same atoms a substituent with more atoms of a given element receives higher priority ($\text{CH}_2\text{CH}_3$ > $\text{CH}_3$)
  • These rules are also known as priority rules in stereochemistry

R and S configuration determination

  • Orient the molecule with the lowest priority substituent pointing away from the viewer ensures a consistent frame of reference for assigning configuration
  • Trace the remaining substituents from highest to lowest priority clockwise direction indicates an R (rectus) configuration counterclockwise direction indicates an S (sinister) configuration
  • Mentally or physically swap the position of the lowest priority substituent with the substituent directly across from it if it is not pointing directly away swapping positions of two substituents inverts the configuration (R becomes S, S becomes R)
  • This process is used to determine the configuration of a stereocenter

Absolute vs relative configurations

  • Absolute configuration refers to the actual spatial arrangement of substituents around a chiral center determined using the Cahn-Ingold-Prelog sequence rules described as R or S configuration
  • Relative configuration compares the arrangement of substituents between two or more chiral centers denoted using stereodescriptors such as "like" or "unlike" diastereomers have different relative configurations
  • Enantiomers have the same relative configuration but opposite absolute configurations one chiral center will be R while the other is S (mirror images)
  • Diastereomers have different relative configurations and may have the same or opposite absolute configurations depends on the specific arrangement of substituents around each chiral center (non-mirror images)
  • Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules
  • Chirality refers to the property of a molecule that is non-superimposable on its mirror image
  • Stereoisomers are isomers that differ only in the spatial arrangement of their atoms
  • Fischer projections are two-dimensional representations of three-dimensional molecules, often used to depict stereochemistry
  • Optical activity is the ability of chiral molecules to rotate plane-polarized light, which is related to their stereochemistry

Key Terms to Review (36)

Sequence rules: Sequence Rules are a set of guidelines used in organic chemistry to determine the priority of substituents attached to a chiral center, aiding in the specification of its configuration. They are essential for assigning the absolute configuration as either R (rectus) or S (sinister) based on the atomic number and connectivity of the substituents.
Chirality centers: A chirality center in organic chemistry is an atom, typically carbon, that has four different groups attached to it, leading to non-superimposable mirror image forms of the molecule. These centers are crucial for determining the 3D spatial orientation of molecules, affecting their chemical behavior and interactions.
Cahn–Ingold–Prelog sequence rules: The Cahn-Ingold-Prelog (CIP) sequence rules are a set of guidelines used to systematically name the spatial arrangement of atoms around a stereocenter, helping to determine the configuration of molecules in organic chemistry. These rules prioritize atoms or groups attached to a chiral center based on atomic number, isotopic mass, and connectivity, facilitating the assignment of R (rectus) or S (sinister) configurations.
Anti stereochemistry: Anti stereochemistry describes the spatial arrangement in a chemical reaction where two substituents are positioned on opposite sides of a double bond or ring structure after the reaction. It is particularly relevant in the halogenation of alkenes, resulting in products where the added atoms are located across from each other.
R configuration: R configuration is a designation used in the Cahn-Ingold-Prelog (CIP) priority rules to describe the spatial arrangement of atoms around a chiral center, indicating that the substituents are arranged in a clockwise direction when viewed from a certain perspective. It stands for "rectus", which is Latin for "right".
Cahn–Ingold–Prelog rules: The Cahn-Ingold-Prelog rules are a set of guidelines used to assign priority to substituents attached to a chiral center in molecules, helping determine the three-dimensional spatial configuration of atoms. These rules are crucial for naming the stereochemistry of organic compounds using the R (rectus) and S (sinister) nomenclature.
S configuration: In organic chemistry, S configuration describes the spatial arrangement of atoms around a chiral center, determined by the sequence rules for specifying configuration, where the arrangement follows a counterclockwise order. It is one of the two possible configurations, the other being R configuration.
Absolute configuration: Absolute configuration is the spatial arrangement of atoms around a chiral center, described as either R (rectus) or S (sinister) based on a set of sequence rules. It defines the 3D orientation of molecule parts and does not change with the molecule's orientation or how it's drawn.
Double bond: A double bond in organic chemistry is a chemical bond between two atoms involving four bonding electrons instead of the usual two. It results in stronger attraction and shorter distance between the bonded atoms compared to a single bond.
Atomic number (Z): The atomic number is the number of protons in the nucleus of an atom, which determines the chemical element's identity and its position on the periodic table. It also influences the atom's chemical behavior in reactions.
Triple bonds: A triple bond is a chemical bond where three pairs of electrons are shared between two atoms. It is the strongest and shortest type of covalent bond found in molecules.
Atomic Number: The atomic number is a fundamental property of an element that represents the number of protons in the nucleus of an atom. It is a unique identifier for each element and is a crucial concept in understanding the structure and behavior of atoms.
Chirality: Chirality is a fundamental concept in organic chemistry that describes the three-dimensional arrangement of atoms in a molecule. It refers to the property of a molecule that is non-superimposable on its mirror image, resulting in the existence of two distinct forms known as enantiomers. Chirality is a crucial factor in understanding the behavior and properties of various organic compounds, including their interactions with living systems.
Stereochemistry: Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects the chemical and physical properties of the substance. It examines the spatial orientation of atoms and their relationship to one another, which is crucial in understanding many organic chemistry concepts.
Triple Bond: A triple bond is a covalent bond in which three pairs of electrons are shared between two atoms, resulting in a very strong and stable chemical connection. This type of bond is particularly important in the context of organic chemistry, as it is a key structural feature in certain classes of compounds known as alkynes.
Chiral Center: A chiral center is a carbon atom with four different substituents attached, resulting in a non-superimposable mirror image. This structural feature is crucial in understanding the concepts of enantiomers, Pasteur's discovery of enantiomers, the sequence rules for specifying configuration, and the nucleophilic addition of HCN to form cyanohydrins.
Enantiomers: Enantiomers are a pair of stereoisomers that are non-superimposable mirror images of each other. They have the same molecular formula and connectivity, but differ in the spatial arrangement of their atoms, resulting in a unique handedness or chirality.
Stereocenter: A stereocenter is a carbon atom in a molecule that is bonded to four different substituents, resulting in a chiral center that can exist in two non-superimposable mirror-image forms called enantiomers. Stereocenters are central to understanding the handedness and configuration of molecules, as well as their interactions in biological systems.
Optical Activity: Optical activity is the ability of certain molecules to rotate the plane of polarized light as it passes through a solution containing those molecules. This phenomenon is directly related to the concept of chirality, where molecules can exist in two non-superimposable mirror-image forms, known as enantiomers.
Stereoisomers: Stereoisomers are molecules that have the same molecular formula and connectivity, but differ in the three-dimensional arrangement of their atoms in space. This spatial arrangement of atoms leads to different physical and chemical properties, even though the atoms are connected in the same way.
Fischer Projection: A Fischer projection is a way of representing the three-dimensional structure of a molecule, particularly organic compounds with tetrahedral carbon centers, on a two-dimensional plane. It is used to depict the relative orientation of substituents around a carbon atom and is crucial for understanding concepts such as enantiomers, diastereomers, and the configuration of sugars.
Prelog: Prelog is a set of rules used to specify the configuration of stereoisomers, particularly in the context of alkene stereochemistry and the assignment of E/Z designations. These rules, developed by the chemist Vladimir Prelog, provide a systematic approach to unambiguously determine the spatial arrangement of atoms around a stereocenter.
Double Bond: A double bond is a covalent chemical bond that forms between two atoms, with the sharing of four valence electrons. This type of bond is commonly found in organic compounds, particularly in alkenes, and is a key structural feature that influences the properties and reactivity of these molecules.
Diastereomers: Diastereomers are a type of stereoisomer that have the same molecular formula and connectivity, but differ in their three-dimensional arrangement of atoms in space. They are not mirror images of each other and do not exhibit the property of chirality.
Ingold: Ingold is a concept in organic chemistry that is primarily used in the context of specifying the configuration of stereoisomers and understanding the stereochemistry of alkenes. It provides a systematic set of rules for assigning priorities to substituents around a stereocenter or double bond, which is crucial for determining the relative orientation of these groups.
Stereodescriptors: Stereodescriptors are the systematic way of describing the three-dimensional arrangement of atoms in a molecule. They provide a standardized method for unambiguously communicating the spatial orientation of substituents around a stereocenter.
Priority Rules: Priority rules are a set of guidelines used to determine the relative importance or precedence of different substituents or functional groups when specifying the stereochemical configuration of organic compounds. These rules are particularly relevant in the context of alkene stereochemistry and the assignment of E/Z designations.
Configuration: Configuration refers to the three-dimensional arrangement of atoms in a molecule. It describes the spatial orientation of atoms and functional groups within a compound, which is crucial in determining the molecule's properties and reactivity.
Sinister: The term 'sinister' refers to something that is evil, harmful, or threatening in nature. In the context of organic chemistry and the sequence rules for specifying configuration, the term 'sinister' is used to describe the direction of rotation of a molecule around a chiral center.
R: In the context of 5.5 Sequence Rules for Specifying Configuration, the term 'R' refers to the priority or precedence assigned to different substituents or functional groups attached to a carbon atom. It is a crucial concept in determining the stereochemical configuration of organic compounds.
Rectus: In the context of the sequence rules for specifying configuration, the term 'rectus' refers to the priority or precedence assigned to atoms or functional groups based on their atomic number. This rule is a crucial component in determining the stereochemistry and configuration of organic molecules.
Absolute Configuration: Absolute configuration refers to the three-dimensional arrangement of atoms around a chiral carbon center. It describes the specific orientation of substituents attached to the chiral carbon, allowing for the unambiguous identification of stereoisomers.
Sequence Rules for Specifying Configuration: Sequence rules, also known as the Cahn-Ingold-Prelog (CIP) rules, are a set of guidelines used to determine the absolute configuration of a chiral molecule. These rules provide a standardized system for assigning priority to substituents around a stereocenter, allowing for the unambiguous specification of the three-dimensional arrangement of atoms in a molecule.
Relative Configuration: Relative configuration refers to the spatial arrangement of atoms or groups within a molecule in relation to a reference point or other atoms, without specifying the absolute stereochemistry. It describes the orientation of substituents around a stereocenter without defining the overall configuration of the molecule.
Cahn: Cahn is a term that refers to the Cahn-Ingold-Prelog (CIP) sequence rules, which are a set of guidelines used to specify the stereochemical configuration of molecules, particularly in the context of alkene stereochemistry and the E/Z designation.
Cahn-Ingold-Prelog Sequence Rules: The Cahn-Ingold-Prelog sequence rules are a set of guidelines used to systematically assign priorities to the substituents around a stereogenic center in organic chemistry. These rules provide a standardized method for specifying the configuration of chiral molecules.