Mass Spectrometry

Principles of Mass Spectrometry

Mass spectrometry is a powerful analytical technique used to determine the molecular weight and structure of organic compounds. Molecules are ionized by electron bombardment to produce a radical cation, which is unstable and fragments into smaller ions and radicals. These fragments are analyzed to deduce structural information.

• Ionization:

• Fragmentation: The unstable radical cation breaks into radicals and cations.

• Analysis: Fragmentation patterns are dictated by the stability of the carbocation formed after bond cleavage.

Example:

• Breaking a C–C bond in isobutane produces a fragment with .

• Stability order: methyl < CH2R < CHR2 < CR3 (most stable).

Infrared Spectroscopy

Fundamentals of IR Spectroscopy

Infrared (IR) spectroscopy is used to identify functional groups in organic molecules by measuring the absorption of IR radiation, which causes molecular vibrations. The position and intensity of absorption bands provide diagnostic information.

• Bond Stretching Frequencies:

  • C–H, O–H, N–H: Bonds to hydrogen appear at higher frequencies.

  • Triple bonds (C≡C, C≡N): Stronger bonds, higher frequency.

  • Double bonds (C=C, C=O, C=N): Intermediate frequency.

  • Single bonds (C–C, C–O, C–N): Lower frequency, fingerprint region.

• Diagnostic Absorptions:

  • C=O stretch: ~1700 cm-1 (intense)

  • O–H stretch: >3000 cm-1 (intense, broad)

Example:

• IR spectrum showing strong C=O and broad O–H absorptions.

Conformational Analysis

Ethane

Conformational analysis examines the spatial arrangement of atoms resulting from rotation about single bonds. For ethane, staggered conformations are more stable than eclipsed conformations due to minimized electron repulsion.

• Staggered conformation: Dihedral angle

• Eclipsed conformation: Dihedral angle

• Stereoelectronic effects: Stabilization arises from hyperconjugation between filled C–H orbitals and empty orbitals.

• Stabilization energy: per interaction

Butane

Butane exhibits several conformations due to rotation about the central C–C bond. The energy of each conformation depends on the relative positions of the methyl groups.

• Staggered (anti-periplanar): Most stable; methyl groups are opposite.

• Gauche: Methyl groups are 60° apart; less stable due to steric strain.

• Eclipsed: Methyl groups are aligned; least stable due to torsional and steric strain.

Example:

• Steric strain occurs when two CH3 groups are only 60° apart (gauche).

Skeletal Structures and Newman Projections

Skeletal structures and Newman projections are two ways to represent the three-dimensional arrangement of atoms in a molecule. Newman projections are especially useful for visualizing conformational isomers.

• Skeletal structure: Shows connectivity of atoms.

• Newman projection: Visualizes the molecule looking down a specific bond axis.

Cyclohexane Conformations

Cyclohexane adopts non-planar conformations to minimize strain. The most stable is the chair conformation, which interconverts via a ring flip. Axial and equatorial positions are exchanged during a ring flip.

• Chair conformation: Minimizes torsional and steric strain.

• Ring flip: Axial H atoms become equatorial and vice versa.

• Substituted cyclohexanes: Bulky groups prefer equatorial positions to minimize 1,3-diaxial repulsions.

• Isomer stability:

  • Trans isomers with two equatorial groups are more stable than cis isomers with one axial and one equatorial group.

Stereochemistry

Enantiomers

Enantiomers are non-superimposable mirror images of each other, arising from the presence of a stereogenic center (usually a tetrahedral carbon with four different substituents).

• Assigning configuration:

  • Assign priorities to groups (Cahn-Ingold-Prelog rules).

  • Orient the molecule so the lowest priority group is away from you.

  • Trace from highest (1) to lowest (3) priority:

    • Clockwise = (R)

    • Anti-clockwise = (S)

Example:

• Sitagliptin (Januvia) and carvone (spearmint) are examples of molecules with stereocenters.

Diastereomers

Diastereomers are stereoisomers that are not mirror images. They differ in the configuration at one or more stereocenters but not all.

• Properties: Diastereomers have different physical and chemical properties.

• Number of stereoisomers: For n stereocenters, maximum possible is .

Sigma Conjugation: Carbocation & Radical Stability

Carbocation Stability

Carbocations are stabilized by sigma conjugation (hyperconjugation) and inductive effects. The stability increases with the number of alkyl groups attached to the positively charged carbon.

Radical Stability

Carbon radicals are also stabilized by sigma conjugation. The stability order parallels that of carbocations.

• Hybridization: Carbon radicals are sp2 hybridized; the singly occupied molecular orbital (SOMO) contains the unpaired electron.

C–H Bond Dissociation Energies (BDEs) & Thermodynamics

C–H BDEs

The bond dissociation energy (BDE) of a C–H bond is the energy required to homolytically cleave the bond, forming a carbon radical and a hydrogen atom. BDEs are influenced by the stability of the resulting radical.

Gibbs Free Energy Formula

The spontaneity of a reaction is determined by the change in Gibbs free energy (), which depends on the change in enthalpy () and entropy ():

• Formula:

• Where is the temperature in Kelvin.

Example:

• Homolytic cleavage of a C–H bond:

Summary Table: Key Concepts

Additional info: Academic context and definitions have been expanded for clarity and completeness. Tables have been inferred and formatted for comparison of stability trends.