5.10 Chirality at Nitrogen, Phosphorus, and Sulfur
2 min read•may 7, 2024
, , and atoms can act as in certain compounds. This adds complexity to molecular structures, affecting their properties and reactivity. Understanding these centers is crucial for predicting and controlling in organic reactions.
at these atoms presents unique challenges, like , which can complicate enantiomer isolation. Techniques to prevent inversion and resolve chiral mixtures are essential tools for chemists working with these compounds in research and industry.
Chirality at Nitrogen, Phosphorus, and Sulfur
Chirality centers of N, P, and S
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- Nitrogen, phosphorus, and sulfur atoms can act as chirality centers when they are sp³ hybridized having four different substituents attached (, , )
- Nitrogen chirality centers commonly found in amines and such as
- Phosphorus chirality centers found in organophosphorus compounds like phosphines, for example
- Sulfur chirality centers found in sulfonium salts and other organosulfur compounds, such as
- These chirality centers exhibit , which is crucial for their stereochemical properties
Nitrogen inversion and enantiomer isolation
- Nitrogen inversion is a low-energy process that occurs in trivalent nitrogen compounds involving the rapid interconversion between two
- on nitrogen passes through the plane of the three substituents leading to an umbrella-like inversion of the configuration
- Results in the rapid equilibration of nitrogen-centered making it difficult to isolate individual enantiomers as they interconvert faster than they can be separated
- Preventing nitrogen inversion can be achieved by:
- Incorporation of nitrogen into a cyclic structure (, )
- Quaternization of the nitrogen atom (ammonium salts)
Configurational stability of chiral compounds
- refers to the ability of a chiral center to maintain its configuration over time
- Chiral phosphines exhibit high configurational stability with inversion barrier much higher compared to nitrogen, for example , a chiral diphosphine ligand used in
- Chiral sulfonium salts display moderate configurational stability with inversion barrier lower than phosphorus but higher than nitrogen, such as , used in
- Factors affecting configurational stability include:
- around the chirality center
- Electronic effects of the substituents
- Presence of lone pairs and their ability to invert
- can occur when configurational stability is low, leading to the loss of optical activity
Chiral resolution techniques
- is used to separate enantiomers of chiral compounds containing N, P, or S centers
- Methods include crystallization of diastereomeric salts, chromatographic separation, and enzymatic resolution
- These techniques are crucial for obtaining pure enantiomers, especially when dealing with compounds that undergo rapid racemization
Key Terms to Review (31)
(R)-2-Methylpyrrolidine: (R)-2-Methylpyrrolidine is a chiral organic compound with a nitrogen atom in the ring structure. It is an important concept in understanding chirality, particularly in the context of nitrogen, phosphorus, and sulfur atoms.
(R)-BINAP: (R)-BINAP is a chiral phosphine ligand that has found widespread use in asymmetric catalysis. Its unique binaphthyl backbone and two phosphine groups create a well-defined chiral environment that can selectively catalyze a variety of organic transformations.
(R)-Ethylmethylphenylsulfonium bromide: (R)-Ethylmethylphenylsulfonium bromide is a chiral sulfur-containing compound with a tetrahedral configuration around the sulfur atom. This term is relevant in the context of understanding chirality at sulfur, as well as the broader concepts of chirality at nitrogen, phosphorus, and other elements.
(R)-Methylphenylphosphine: (R)-Methylphenylphosphine is a chiral organophosphorus compound with a stereogenic center at the phosphorus atom. It is an important compound in the context of understanding chirality at phosphorus, as well as its relationship to chirality at nitrogen and sulfur.
(S)-Ethylmethylphenylsulfonium tetrafluoroborate: (S)-Ethylmethylphenylsulfonium tetrafluoroborate is a chiral sulfur-containing compound with a tetrahedral configuration around the sulfur atom, making it an example of chirality at sulfur. This compound is often used in organic chemistry as a reagent or intermediate in various reactions.
Amines: Amines are a class of organic compounds derived from ammonia (NH3) by the replacement of one or more hydrogen atoms with alkyl or aryl groups. They are characterized by the presence of a nitrogen atom with a lone pair of electrons, giving them basic properties and the ability to act as nucleophiles in chemical reactions.
Ammonium Salts: Ammonium salts are a class of chemical compounds formed by the reaction between ammonia (NH3) and an acid. They are characterized by the presence of the ammonium cation (NH4+) and a corresponding anion from the acid. These salts are widely used in various applications, including agriculture, industrial processes, and household products.
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.
Asymmetric Catalysis: Asymmetric catalysis is a powerful synthetic strategy that employs chiral catalysts to selectively produce one enantiomer of a chiral product over the other. It is a crucial technique in organic chemistry for the synthesis of optically pure compounds, which are essential in the pharmaceutical, agrochemical, and fine chemical industries.
Asymmetric Synthesis: Asymmetric synthesis is a chemical reaction that produces a chiral molecule in a stereoselective manner, resulting in the formation of one enantiomer or diastereomer in excess over the other. This concept is crucial in understanding various topics in organic chemistry, including Pasteur's discovery of enantiomers, chirality at nitrogen, phosphorus, and sulfur, prochirality, chirality in nature and chiral environments, and the synthesis of amino acids.
Azetidines: Azetidines are a class of organic compounds containing a four-membered ring with one nitrogen atom. They are important in the context of understanding chirality at nitrogen, phosphorus, and sulfur atoms, as the presence of the nitrogen atom within the ring can lead to the formation of stereoisomers.
Aziridines: Aziridines are a class of organic compounds containing a three-membered ring with one nitrogen atom and two carbon atoms. They are important intermediates in organic synthesis and have unique chemical properties due to the strained nature of the aziridine ring.
Chiral Resolution: Chiral resolution is the process of separating a racemic mixture, which contains equal amounts of two enantiomeric forms of a compound, into its individual enantiomers. This is an important technique in organic chemistry, particularly in the context of understanding chirality at nitrogen, phosphorus, and sulfur.
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.
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.
Configurational Stability: Configurational stability refers to the ability of a molecule to maintain its specific three-dimensional arrangement or configuration under various conditions. It is an important concept in the context of chirality, which is the property of a molecule to exist in non-superimposable mirror-image forms, and is particularly relevant when discussing the stability and reactivity of chiral molecules.
Enamines: Enamines are organic compounds formed by the reaction between a secondary amine and an aldehyde or ketone, characterized by the presence of a nitrogen atom connected to a carbon-carbon double bond. They are the result of nucleophilic addition of amines to carbonyl compounds followed by dehydration.
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.
Lone Pair: A lone pair, also known as an unshared pair, refers to a pair of valence electrons in an atom that are not involved in covalent bonding with other atoms. These electron pairs are not shared with neighboring atoms and remain solely within the atom's electron cloud.
Nitrogen: Nitrogen is a chemical element that is essential for life, playing a crucial role in the structure and function of many organic molecules, including those found in living organisms. It is a key component in various biological processes and is a fundamental building block of proteins, nucleic acids, and other biomolecules.
Nitrogen Inversion: Nitrogen inversion is a process where the nitrogen atom in a molecule temporarily flips its position in space, leading to the interconversion of stereoisomers. This phenomenon is particularly relevant in the context of chirality at nitrogen, phosphorus, and sulfur atoms.
Phosphines: Phosphines are a class of organic compounds containing a phosphorus atom bonded to one or more hydrocarbon groups. They are important in organic chemistry due to their unique properties and applications, particularly in the context of chirality at nitrogen, phosphorus, and sulfur.
Phosphorus: Phosphorus is a chemical element that is essential for various biological processes in living organisms. It is a key component of many important molecules, such as DNA, RNA, and ATP, and plays a crucial role in cellular energy production, bone and teeth formation, and nerve function.
Pyramidal Configurations: Pyramidal configurations refer to the three-dimensional spatial arrangement of atoms or groups around a central atom, typically observed in molecules with a tetrahedral or trigonal pyramidal geometry. This structural feature is particularly relevant in the context of chirality, where it can lead to the formation of stereoisomers.
Quaternary ammonium salts: Quaternary ammonium salts are compounds where an ammonium ion (NH4+) has four organic groups attached to it, typically through a nitrogen atom, and is paired with a negatively charged ion (anion). These substances are known for their surfactant and antiseptic properties.
Racemization: Racemization is the process by which a chiral molecule is converted into a racemic mixture, containing equal amounts of the two enantiomeric forms. This phenomenon is particularly relevant in the context of chirality at nitrogen, phosphorus, and sulfur, the SN1 reaction, peptide synthesis, and automated peptide synthesis using the Merrifield solid-phase method.
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.
Steric Hindrance: Steric hindrance, also known as steric strain or steric effect, refers to the repulsive forces that arise between atoms or groups of atoms in a molecule due to their physical size and spatial arrangement. This phenomenon can significantly impact the stability, reactivity, and conformations of organic compounds.
Sulfonium Salts: Sulfonium salts are a class of organic compounds containing a positively charged sulfur atom bonded to three organic substituents, forming a tetrahedral structure. These salts are important in the context of understanding chirality at sulfur, nitrogen, and phosphorus centers.
Sulfur: Sulfur is a chemical element with the atomic number 16. It is an essential mineral found in the human body and plays a crucial role in various biological processes. Sulfur is particularly relevant in the context of understanding the hybridization of nitrogen, oxygen, phosphorus, and sulfur, as well as the concept of chirality at nitrogen, phosphorus, and sulfur.
Tetrahedral Geometry: Tetrahedral geometry refers to the three-dimensional spatial arrangement of atoms or groups of atoms in a molecule, where the central atom is bonded to four other atoms or groups in a symmetrical tetrahedral configuration. This geometric structure is a fundamental concept in understanding the structure and properties of various organic and inorganic compounds.