Absolute configuration

6 Key excerpts on "Absolute configuration"

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  Organic Chemistry

  An Acid-Base Approach, Third Edition

  • Michael B. Smith(Author)
  • 2022(Publication Date)
  • CRC Press

    (Publisher)

  Cahn-Ingold-Prelog selection rules (the CIP rules) . These rules for determining stereochemistry have been formalized and expanded by IUPAC.

  Both enantiomers of 1-bromo-1-chloroethane are shown, drawn in line notation and in Fischer projection. All atoms attached to a stereogenic carbon atom are assigned a priority of importance for each attached atom. The spatial arrangement of these atoms about the central carbon will determine the Absolute configuration of each molecule.

  First, assign a priority based on the atomic mass of each atom. 1-Bromo-1-chloroethane, for example, has a H, Cl, Br, and a CH3 group attached to the stereogenic carbon. The mass of the group (–CH3 ) is not used but rather the mass of the carbon atom attached to the stereogenic atom . The atomic masses of Br, Cl, H, and C are compared, and the order of descending atomic mass is Br > Cl > C > H. The priority letters a , b , c, and d are assigned for each atom in a tetrahedral representation of 1-bromo-1-chloroethane. The “a” has the highest priority and “d” the lowest priority: Br = a, Cl = b, C = c, and H = d (see A in Figure 9.4 ).

  Figure 9.4

  Assignment of Absolute configuration for 1-brnomo-1-chloroethane using the steering wheel model.

  Before the Absolute configuration can be assigned, the model must be viewed with the lowest priority group (d) projected to the rear (180° from the viewer). The a-b-c atoms form the base of the tetrahedron projected to the front, as illustrated in Figure 9.4 . Starting with A, the tetrahedron is tipped back and slightly to the right so the d group is moved to the rear as the a group and the c group tip up. The b group remains more or less in the same position to give B. Atoms a-b-c form the base of the tetrahedron, and this view can be imagined as the steering wheel of an old-time car. Indeed, this representation is called the steering-wheel model (see Figure 9.4 ). An imaginary arrow can be drawn to generate the arc of a circle from the highest priority atom (a) toward the next highest priority atom (b) and finally toward (c). If this imaginary arrow proceeds in a clockwise direction , the term (R) for rectus (Latin for right) is used. If this imaginary arrow proceeds in a counterclockwise direction , the term (S) for sinister (Latin for left) is used. In this example, the imaginary arrow from a → b → c proceeds in a counterclockwise direction, so it is labeled the (S)-configuration. The name is (1S)-bromo-1-chloroethane. Using the same protocol and priority scheme for the enantiomer leads to an arrangement in which the arrow from a → b → c proceeds in a clockwise direction and the name is (1R)-bromo-1-chloroethane. To summarize, the Absolute configuration for an enantiomer is determined by assigning priorities a-d for atoms connected to a stereogenic center. Attach these atoms to a tetrahedron with the stereogenic carbon in the center. Rotate the molecule so the (d) group is projected to the rear. Trace a circle from a → b → c. If the direction a → b → c is clockwise, the Absolute configuration is (R) but if the direction is counterclockwise, the Absolute configuration is (S

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  Mathematical Stereochemistry

  • Shinsaku Fujita(Author)
  • 2015(Publication Date)
  • De Gruyter

    (Publisher)

  78

  13.1 Absolute configuration

  13.1.1 Single Pair of Attributes ‘Chirality/Achirality’ in Modern Stereochemistry

  In the glossary of the IUPAC Recommendations 1996 [1 ], the term configuration is defined as “In the context of stereochemistry, the term is restricted to the arrangement of atoms of a molecular entity in space that distinguishes stereoisomers, the isomerism between which is not due to conformation differences. See also Absolute configuration and relative configuration”. And then, the term Absolute configuration is defined as “The spatial arrangement of the atoms of a chiral molecular entity (or group) and its stereochemical description, e.g., R or S.”

  The term ‘stereogenic’ has later been proposed to rationalize the foundations of R/S- stereodescriptors [2 ]. Helmchen [3, Section 1.3 ] has pointed out that the term chirality element is one of problematic terms: “This previously common term should be used with care. More appropriate is the term stereogenic unit”. However, Helmchen [3, Table 1] maintains the usage of the terms ‘chirality center’ (C ‘chirality units’) and ‘pseudoasymmetric center’. (C ‘pseudoasymmetric units’). Moreover, Rule 91.1.1.1 of Provisional Recommendations 2004 [4 ] refers to the term ‘stereogenic unit’ and points out the presence of three kinds of stereogenic units (a central atom such as a chirality center, a central bond such as a chirality axis, and a double bond). Then, it states “... A chirality center, formerly known as an ‘asymmetric atom’, is the classical example of a stereogenic unit.” and shows an example of assigning an R-descriptor to a ‘chirality center’ of Xabcd.

  The term ‘stereogenic centers’ is used to designate a pair of Cl-substituted carbons in cis- and trans-1,3-dichlorocyclobutanes, where interchange of two ligands (Cl and H) at a ‘stereogenic’ center leads to a stereoisomer [5, Fig. 3.8

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  Basic Stereochemistry of Organic Molecules

  • Rose Marie O. Mendoza(Author)
  • 2020(Publication Date)
  • Arcler Press

    (Publisher)

  Right now, scalar physical properties of the items, for example, their dissolving focuses are extraordinary, just like the total estimations of their optical pivots. As opposed to utilizing a stereochemical show, the enantiomers of lactic corrosive can be recognized through scalar physical properties. This outcome is as per the general rule that the collaboration of a chiral species categories with the antipodal individuals from any enantiomeric pair (even with its own sort) is a diastereomeric procedure, for example, it is diverse from a scalar perspective. Basic Stereochemistry of Organic Molecules 140 Indeed, even the various headings of optical turn saw with enantiomers might be followed back to diastereomeric communications. 5.6. Absolute configuration The exact or detailed arrangement of the substituents at a stereogenic center is known as the Absolute configuration of that particular molecule. If an individual has to draw the structure, then he or she can use the R-and S-notation system in order to locate the Absolute configuration of that structure of that particular molecule. It is a more considerably a difficult task in order to be able to locate the Absolute configuration to an actual sample of a molecule (that is a compound in a bottle). This process is can be achieved with the help of solving the x-ray crystal structure of a molecule (which is a method that is not always readily available), with the help of spectroscopic methods, or possibly with the help of inference based on chemical reactions of known specific stereochemistry involving a compound whose Absolute configuration is known.

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  Studies in Natural Products Chemistry

  • (Author)
  • 2014(Publication Date)
  • Elsevier

    (Publisher)

  [1] . Our objective here, however, is much more modest. In this chapter, we will be especially interested in molecular chirality, which is the manifestation of chirality in the three-dimensional arrangement of atoms in a given molecule, known as Absolute configuration (AC).

  This feature is particularly important for natural products chemistry since natural compounds are predominantly chiral and generally enantiomerically enriched. As a result, stereochemical discrimination may be considered the ultimate refinement of chemical communication in nature [2] . Chirality is, therefore, a key concept to understanding the interactions of biologically active compounds with their protein targets, as well as the biosynthetic pathways leading to their formation. Based on that, the unambiguous determination of the AC and conformations of chiral compounds is critical for the studies of natural products and biomolecular systems [3] .

  Nevertheless, despite its cornerstone importance, determining the AC of chiral molecules is not a trivial task. Enantiomers, which are defined as a pair of molecular entities which are mirror images of each other and nonsuperposable [4] , share, in an achiral environment, basically the same physical and chemical properties that make them indistinguishable in many aspects. Even though X-ray crystallography and nuclear magnetic resonance (NMR) methods are still considered golden standards to stereochemical studies, some requirements may limit their applicability. The former requires a well-defined single crystal and the presence of at least one strong anomalous scatterer (a heavy atom); otherwise an internal chiral reference of known AC has to be introduced in the crystal structure [5 ,6 ]. The latter is intrinsically achiral and can be used only if a chiral auxiliary is added during the experiment. NMR auxiliaries may be chiral derivatizing agents (CDAs), chiral solvation agents (CSAs), ion-paring agents, chiral hosting compounds, metal complexes, and liquid crystals [7]

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  Stereochemistry

  Basic Concepts and Applications

  • M. Nógrádi(Author)
  • 2013(Publication Date)
  • Pergamon

    (Publisher)

  Different configurations correspond to different arrangements of these atoms. Different conformations of molecules of the same constitution and configuration differ by their torsion angles around single bonds. Conformational changes may, or may not, affect the configuration. The topic of configuration will be discussed first in Section 1.1 followed by that of conformation in Section 1.2 but it should be stressed that the two terms are complementary. 2 N6grfdi 1 1.1 CONFIGURATION AND CHIRALITY 1.1.1 Molecular geometry Although stereochemical studies may be undertaken (and indeed were pursued for many decades) without any knowledge of the real dimensions of molecules, more meaningful results are achieved if the geometrical parameters associated with the molecules of interest are known. For this reason, these parameters will be defined first. Molecules are composed of atoms, while atoms consist of a nucleus sur-rounded by a number of electron shells. The structures of the latter lie in the domain of quantum mechanics and need not be considered further here. In general, stereochemistry is concerned with the relative positions of atomic nuclei; the electronic structures associated with the latter are unimportant except for the fact that they do influence rotation about bonds. Thus rotations around single bonds are fast in comparison with those about double bonds. When a system consists of a single atom, the geometry may be expressed in terms of a single parameter, the van der Wools 9 radius (r) (Fig. la). Van der Waals* radii may be defined in terms of the energy profile obtained when two non-bonded neutral atoms approach each other (Fig. lb). As the internuclear distance decreases, the initial weak attractive interaction be-tween the atoms is replaced by a strong repulsion.

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  Vibrational Optical Activity

  Principles and Applications

  • Laurence A. Nafie(Author)
  • 2011(Publication Date)
  • Wiley

    (Publisher)

  In a related paper, the Absolute configuration of R -(−)-iodochlorofluoromethane was determined by VCD measurement and ab initio calculation (Figure 10.2). The molecule is of interest in the search for parity violation of molecular origin (Soulard et al., 2006). Figure 10.2 Comparison (left panel) of measured depolarized right-angle ICP-Raman (I R z I L z) and -ROA (I R z −I L z), a and d, respectively, for the neat liquid (–)-enantiomer of bromochlorofluoromethane with the corresponding ab initio calculation of the R -enantiomer showing close agreement for all major bands (Costante et al., 1997). Reproduced with permission from John Wiley & Sons (Costante, J., Hecht, L., Polavarapu, P.L., Collet, A., and Barron, L.D. (1997) Absolute-Configuration of Bromochlorofluoromethane from Experimental and Ab-Initio Theoretical Vibrational Raman Optical-Activity. Angew. Chem. Int. Ed. 36, 885–887. Fig. 2, p. 886. John Wiley & Sons). Comparison (right panel) of measured IR and VCD spectra in the gas phase with rotational bands shapes of the (–)-enantiomer of iodochlorofluoromethane with the corresponding DFT calculation, without rotational bandshapes of the R -enantiomer. Reproduced with permission from Elsevier Science Ltd. (Soulard et al., 2006a) 10.2.2 Comparison with X-Ray Crystallography For many years, the gold standard for AC determinations has been anomalous X-ray crystallography by the method of Bijvoet (Bijvoet et al., 1951). The requirement of this method is a pure single crystal of the molecule. A typical further, but not absolute requirement is that a heavy atom (beyond C, N, O) be present in the crystal as a phase reference for the X-ray scattering. Obtaining such single-crystals in general is an art and obtaining a crystal of sufficient size and purity may take a long time, on the order of days or weeks

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