Organic Chemistry- Exam II

Chirality and Proton Signaling

isomers

• Compounds with the same molecular formula but different properties.

constitutional isomers

• same molecular formula: The number and type of atoms are identical in both molecules.

• Different connectivity: The way atoms are linked differs — for example, which carbon atoms are bonded to which, or where a functional group is located

  Chemistry Learner+1.

• Different properties: Because their structures differ, constitutional isomers often have distinct physical (e.g., boiling point, polarity) and chemical properties

stereoisomers

Atoms have the same connectivity but differ in their specific arrangement in space (e.g., cis/trans isomers).

configuration vs configuration

• Conformation: Different arrangements due to rotation around single bonds

• Configuration: The absolute arrangement of groups in three-dimensional space

Key characteristics of a identifying a chirality center (achiral vs chiral)

Achiral: A molecule is achiral if it and its mirror image are superimposable (identical). All bonds and atoms line up.

• The prefix "a-" means "not" (e.g., asymptomatic = not symptomatic).

Chiral: A molecule is chiral if it and its mirror image are non-superimposable (cannot be perfectly aligned).

• The term "chiral" comes from the Greek word for "hand."

• Analogy: Your left and right hands are mirror images but are non-superimposable.

enantiomers

Stereoisomers that are non-superimposable mirror images of each other.

• Can not line up all atoms and bonds together to get a mirror image

Methods of determining a chirality center

1. Superimposability Test:

   • Draw the molecule in 3D.

   • Draw its mirror image.

   • Attempt to superimpose the mirror image onto the original molecule by rotating it in space (without breaking bonds).

   • If they superimpose, the molecule is achiral. If not, it is chiral.

   • Example: CH2BrCl is achiral (superimposable mirror image). CHBrClF is chiral (non-superimposable mirror image).

2. Chirality Center (Stereocenter, Asymmetric Carbon):

   • An atom (typically carbon) bonded to four different groups.

   • Labeled with an asterisk (*).

   • Example: CH2BrCl has no chirality center because the two hydrogens are identical. CHBrClF has one chirality center (the carbon) because Br, Cl, F, and H are all different.

   • Cyclic Molecules: To identify chirality centers in rings, compare the two paths around the ring from the potential center. If the paths are different, it's a chirality center.

     • Example A (symmetric ring): No chirality centers.

     • Example B (asymmetric ring): One chirality center.

Relationship between number of chirality centers and chiraliy

• Zero Chirality Centers: Generally achiral (rare exceptions exist, e.g., chirality axis).

• One Chirality Center: Always chiral.

• Two or More Chirality Centers: May or may not be chiral (requires further evaluation, discussed later).

plane of symmetry

• If a molecule possesses an internal plane of symmetry (dividing it into two identical mirror halves), it is achiral meso.

• Consider molecular rotation to find potential planes of symmetry.

Properties of enantiomers

• Identical Chemical and Physical Properties:

  • Same boiling point, melting point, density, solubility in achiral solvents.

  • Same reactivity with achiral reagents.

• Differing Properties:

  • Interaction with Chiral Substances: Enantiomers interact differently with other chiral molecules (e.g., biological receptors, enzymes). This explains the thalidomide example.

  • Interaction with Plane-Polarized Light (Optical Activity):

    • Chiral compounds rotate the plane of plane-polarized light.

    • Achiral compounds do not rotate plane-polarized light; they are optically inactive.

    • Specific Rotation: Enantiomers rotate plane-polarized light by the same magnitude but in opposite directions.

      • Dextrorotatory (d or +): Rotates light clockwise.

      • Levorotatory (l or -): Rotates light counter-clockwise.

    • Racemic Mixture (Racemate): A 50/50 mixture of two enantiomers. It is optically inactive because the rotations cancel each other out.

Absolute Configuration (assigning R/S)

• Purpose: To systematically label and distinguish between enantiomers, especially since they have identical IUPAC names.

• Con-Ingold-Prelog (CIP) Rules / Sequence Rules: A set of rules used to assign priority to the four different groups attached to a chirality center.

• This priority assignment is the first step in determining the absolute configuration (R or S) of a chirality center.

• R/S notation is used to label the absolute configuration of a chirality center.

• A chirality center is typically a carbon atom bonded to four distinct groups.

• Before assigning R/S, the four groups attached to the chirality center must be ranked by priority

Assigning prioity to atoms connected to chirality center

• Rule 1: Atomic Number

  • Assign priorities (1 = highest, 4 = lowest) based on the atomic number of the atoms directly bonded to the chirality center.

  • Higher atomic number corresponds to higher priority.

  • Example: Cl (atomic number 17) > N (7) > C (6) > H (1).

• Rule 2: Tie-Breaking (Next Atom)

  • If the atoms directly bonded to the chirality center are identical, move outward along each chain to the next set of atoms.

  • Priority is determined at the first point of difference. Do not sum atomic numbers.

  • Compare the atomic numbers of the atoms attached to the tied atoms.

  • Example: Isopropyl (C bonded to 2 C, 1 H) > Ethyl (C bonded to 1 C, 2 H) > Methyl (C bonded to 3 H).

  • Example with further tie-breaking: A CH2Cl group would have higher priority than a CH2CH2Br group because the chlorine (Cl) breaks the tie at the first point of difference (Cl vs. C), even though bromine (Br) has a higher atomic number than carbon.

• Rule 3: Tie-Breaking (Isotopes)

  • If two atoms have the same atomic number but are different isotopes, the heavier isotope receives higher priority.

  • Example: Deuterium (D) > Hydrogen (H).

• Rule 4: Multiple Bonds

  • Treat multiple bonds as if they are single bonds to an equivalent number of atoms.

  • Double Bond (e.g., C=C): The carbon is treated as being single-bonded to two carbons. The other carbon is also treated as being single-bonded to two carbons.

  • Double Bond (e.g., C=O): The carbon is treated as being single-bonded to two oxygens. The oxygen is treated as being single-bonded to two carbons.

  • Triple Bond (e.g., C≡N): The carbon is treated as being single-bonded to three nitrogens. The nitrogen is treated as being single-bonded to three carbons.

  • This "phantom atom" approach allows for direct comparison with single-bonded groups.

Assigning R/S configuration

1. Assign Priorities: Use the CIP rules to assign priorities 1, 2, 3, and 4 to the four groups.

2. Orient the Molecule: Position the molecule so the lowest priority group (priority 4) is pointed away from the viewer (typically represented by a dashed wedge).

3. Trace the Path: Trace a path from priority 1 to 2 to 3.

   • If the path is clockwise, the configuration is R (from Latin rectus, meaning right).

   • If the path is counter-clockwise, the configuration is S (from Latin sinister, meaning left).

4. Enantiomers: Molecules that are non-superimposable mirror images (enantiomers) will have opposite R/S configurations at their corresponding chirality centers. Identical molecules will have the same R/S configuration.

•  Rotate Method:

  • Mentally (or using a model) rotate the entire molecule in space until the lowest priority group (4) is pointed away (on a dash).

  • Then, assign R/S by tracing 1→2→3.

  • This method involves physically moving the molecule without breaking bonds.

Fischer Projections- Purpose

• Purpose: A simplified 2D representation of 3D stereochemistry, particularly useful for molecules with multiple chirality centers.

Fischer Projections- Drawing convention

• Drawing Convention:

  • The chirality center is at the intersection of horizontal and vertical lines.

  • Horizontal bonds are understood to be coming towards the viewer (wedges).

  • Vertical bonds are understood to be going away from the viewer (dashes).

  • The carbon atom at the center is not explicitly drawn, and no wedges or dashes are used.

Fischer Projection- Interpretation

• Fischer projections are not flat; they still convey 3D information.

• To assign R/S from a Fischer projection, it is often helpful to convert it back to a wedge-and-dash representation.

• Conversion Tip: When converting from Fischer to wedge-and-dash, imagine grabbing the horizontal bonds and moving them into the plane. The top vertical group will then pop forward (wedge), and the bottom vertical group will go back (dash).

Molecules with multiple chirality centers- determining max stereoisomers

• Maximum Number of Stereoisomers: (2^n), where (n) is the number of chirality centers.

  • One chirality center: 2 stereoisomers (a pair of enantiomers).

  • Two chirality centers: Maximum of 4 stereoisomers.

Molecules with multiple chirality centers- drawing stereoisomers

• Drawing Stereoisomers (Systematic Approach):

  • Draw one stereoisomer (e.g., with specific R/S configurations).

  • Draw its mirror image, which will be its enantiomer (opposite R/S at all centers).

  • Create a third stereoisomer by inverting the configuration at one chirality center of the first molecule (e.g., swapping two groups). This creates a diastereomer.

  • Draw the mirror image of the third stereoisomer.

Molecules with multiple chirality centers- Identical compounds

• Have the same configuration at every chirality center.

Molecules with multiple chirality centers- enantiomers

• Non-superimposable mirror images with opposite configurations at all chirality centers.

Molecules with multiple chirality centers- diastereomers

• Stereoisomers that are not mirror images. They can have some chirality centers with the same configuration and others switched.

  • Example: Cis/trans isomers of disubstituted cyclohexanes are diastereomers, even without chirality centers.

Fischer projections for multiple chirality centers

• Represent molecules in an eclipsed conformation.

• Horizontal bonds come towards the viewer, vertical bonds go away.

• The carbon-carbon bond between chiral centers lies in the plane.

Meso compounds

• Definition: An achiral compound that contains chirality centers but is overall achiral due to an internal plane of symmetry.

• Identification: When systematically drawing all possible stereoisomers for a molecule with multiple chirality centers, a meso compound is identified when a stereoisomer is superimposable on its own mirror image, meaning it is achiral despite having chiral centers.

Spectroscopy

• To determine molecular structure, as structure dictates properties. Spectroscopy provides structural information by observing how energy interacts with molecules.

Energy and electromagnetic spectrum

• Different energy sources probe different chemical changes, yielding complementary structural information.

• Energy Formula: (\Delta E = h\nu = hc/\lambda), where (\Delta E) is the energy gap, (h) is Planck's constant, (\nu) is frequency, (c) is the speed of light, and (\lambda) is wavelength.

• A photon of appropriate energy must be absorbed for a transition to occur.

NMR spectroscopy

significance: Considered the most powerful technique for organic chemists.

information provided: Structural and connectivity information about the carbon-hydrogen framework.

NMR spectroscopy - types of experiments

• Types of NMR Experiments:

  1. Proton NMR ((^1)H NMR): Determines the type and number of hydrogen atoms.

  2. Carbon NMR ((^{13})C NMR): Determines the chemical environments/types of carbons.

  3. Other Nuclei: Can be performed on nuclei with odd mass numbers (e.g., (^{19})F, (^{31})P) or odd atomic numbers (e.g., (^2)H, (^{14})N) for simpler spectra.

• Energy Source: Radio frequency (RF).

  1. Long wavelength, low frequency (60-1000 MHz).

  2. Probes nuclear spins (not electron spins).

NMR spectroscopy- Theory overview (nuclear spins)

1. A proton is a spinning charged particle, creating a magnetic field.

2. In the absence of an external magnetic field, nuclear spins are randomly aligned.

3. In an external magnetic field ((B_0)), spins align either with (lower energy) or against (higher energy) the field.

4. The energy difference between these states is (\Delta E).

5. Spin Flip: Absorption of an RF photon matching (\Delta E) causes a nucleus to transition from a lower to a higher energy state.

6. Resonance: When a nucleus undergoes a spin flip, it is in resonance; the photon frequency is the resonant frequency.

NMR spectroscopy- instrumentation

1. A magnet holds the sample, which is dissolved in a tube.

2. A computer controls the RF pulse sequence and records data.

3. MRI (Magnetic Resonance Imaging) uses the same principles.

4. Stronger magnets lead to larger (\Delta E) and require larger resonant frequencies.

NMR spectroscopy- structural information from NMR

1. The energy gaps for protons vary based on their chemical environment.

2. Nuclear Shielding: Electron density around a nucleus shields it from the external magnetic field.

   • More electron density = more shielded = smaller effective magnetic field = lower resonant frequency.

   • Less electron density = less shielded = larger effective magnetic field = higher resonant frequency.

NMR spectroscopy- NMR spectrum appearance

1. Y-axis: Intensity (taller peak/larger area = more intense signal).

2. X-axis: Chemical Shift ((\delta)) in parts per million (ppm).

   • Standardization: Chemical shift is a ratio: (observed shift in Hz) / (spectrometer frequency in MHz). An internal standard, typically Tetramethylsilane (TMS), is set to 0 ppm.

   • Scale: 0 ppm (right) to ~12 ppm (left); numbers increase from right to left.

NMR Spectroscopy- four core perspective factors in proton NMR

1. Position of Signals (Chemical Shift): Indicates the specific electronic environment of the proton.

2. Number of Signals: Reveals the number of chemically distinct types of protons.

3. Intensity of Signals (Peak Integration): Area under the peak is proportional to the number of hydrogens contributing to that signal.

4. Splitting/Multiplicity: Provides information about adjacent protons.

Chemical shift: shielding

• Occurs when a nucleus is surrounded by high electron density.

• Electrons create an induced magnetic field that opposes the external magnetic field (B₀).

• The nucleus experiences a reduced effective magnetic field.

• Requires a lower radiofrequency for spin flip (resonance).

• Appears "upfield" (closer to 0 ppm) in the NMR spectrum.

• Example: Methane (CH₄) hydrogens appear at ~0.23 ppm.

Chemical shift- deshielding

• Deshielding:

  • Occurs when a nucleus has less electron density surrounding it.

  • The nucleus experiences a greater fraction of the external magnetic field.

  • Requires a higher radiofrequency for spin flip.

  • Appears "downfield" (larger ppm values) in the NMR spectrum.

• Factors Causing Deshielding:

  • Electronegative Atoms: Electronegative atoms (e.g., Cl) pull electron density away from adjacent hydrogens, making them more deshielded.

    • Example: CH₃Cl hydrogens appear at ~3 ppm, significantly more deshielded than CH₄.

  • Hybridization:

    • sp² hybridized carbons (vinyl, aromatic protons): Hydrogens on sp² carbons are more deshielded than those on sp³ carbons.

    • Pi electrons in sp² systems create an induced magnetic field that reinforces the external magnetic field (B₀).

    • This effect is enhanced in aromatic systems (e.g., benzene), where a "ring current" leads to significant deshielding (6.5-8.5 ppm).

    • Result: Larger chemical shift values (downfield).

  • sp hybridized carbons (alkyne protons):

    • Despite having two pi bonds, alkyne protons are more shielded than sp² protons.

    • The perpendicular orientation of the two pi bonds in alkynes creates an induced magnetic field that opposes the external magnetic field.

    • Result: Smaller chemical shift values (upfield relative to sp²).

Number of signals: chemical equivalence

• The number of signals in a proton NMR spectrum indicates the number of different types of chemically equivalent hydrogens in a molecule.

Number of signals: chemical equivalent hydrogens

• Are in the same chemical environment.

• Experience the same degree of shielding/deshielding.

• Give rise to a single NMR signal.

Number of signals: chemical non-equivalent hydrogens

• Are in different chemical environments.

• Experience different degrees of shielding/deshielding.

• Give rise to separate NMR signals.

Examples

• Dimethyl ether (CH₃OCH₃): All six hydrogens are chemically equivalent, resulting in one signal.

• Methanol (CH₃OH): The three CH₃ hydrogens are equivalent to each other, but different from the OH hydrogen, resulting in two signals.

Determining Equivalence: The CH to CZ Substitution Test

• This test helps determine if hydrogens are chemically equivalent, especially in ambiguous cases.

• Procedure: Replace one hydrogen at a time with a hypothetical test group 'Z'.

Analysis of CZ Substitution Test

• Analysis of Resulting Structures:

  • Homotopic Protons: If substitution at different hydrogens yields the same compound, the hydrogens are homotopic and chemically equivalent.

  • Enantiotopic Protons: If substitution at different hydrogens yields enantiomers, the hydrogens are enantiotopic and chemically equivalent.

  • Diastereotopic Protons: If substitution at different hydrogens yields diastereomers or constitutional isomers, the hydrogens are diastereotopic and chemically non-equivalent (will produce different signals).

Examples of CH to CZ test

• Ethanol (CH₃CH₂OH): The two hydrogens on the CH₂ group are enantiotopic, meaning they are chemically equivalent and contribute to one signal.

• Molecule with a Chiral Center: If a carbon adjacent to a chiral center has two hydrogens, these hydrogens are often diastereotopic and will appear as two distinct signals.

• n-Pentane (CH₃CH₂CH₂CH₂CH₃):

  • The CH₃ groups at the ends (C1 and C5) are equivalent.

  • The CH₂ groups at C2 and C4 are equivalent.

  • The CH₂ group at C3 is unique.

  • Applying the CH to CZ test confirms that hydrogens on C2 and C4 are equivalent, while hydrogens on C2 and C3 are non-equivalent.

  • Result: 3 signals (one for CH₃, one for C2/C4 CH₂, one for C3 CH₂).

Integration Peak Area and Hydrogen Count

• Integration refers to the area under each signal in the NMR spectrum.

• The integral value is proportional to the number of hydrogens contributing to that signal.

• Representation:

  • Often shown as an "integral trace" (a step-like curve where the height of each step corresponds to the relative area).

  • Can also be given as numerical values, which may need to be simplified to the lowest whole-number ratio to represent the relative number of hydrogens.

• Example: For n-pentane, if the signals correspond to 6 (CH₃), 4 (C2/C4 CH₂), and 2 (C3 CH₂) hydrogens, the integral ratio would be 6:4:2, which simplifies to 3:2:1.

Special Cases for Equivalence: Restricted Rotation

• Diastereotopic protons can also arise from restricted rotation within a molecule.

• Cycloalkanes: Due to restricted rotation around C-C bonds in a ring, hydrogens in different spatial relationships (e.g., cis vs. trans to a substituent) can be diastereotopic.

  • Example: In chlorocyclopropane, hydrogens on adjacent carbons that are cis to the chlorine are in a different environment than those that are trans, leading to multiple signals.

• Alkenes: The pi bond in alkenes restricts rotation, which can also lead to diastereotopic protons.

NMR Splitting: Position of signals and peak integration

• Position of Signals: Determined by the chemical environment, indicating the number of equivalent proton groups.

• Peak Integration: Represents the number of hydrogens contributing to an individual signal, corresponding to the area under the curve.

NMR Splitting: Spin Multiplicity/ spin-spin protons

• Spin Multiplicity / Spin-Spin Splitting:

  • Refers to interactions between hydrogens on neighboring carbon atoms.

  • Adjacent/Neighboring Protons: Defined as hydrogens that are three bonds away from each other.

  • Non-equivalent protons on adjacent atoms create slight differences in the magnetic field, causing signals to split.

  • This splitting pattern is crucial for understanding how different molecular fragments are connected.

Mechanism of signal splitting

• Molecule Analysis:

  • Signals: Two distinct signals are expected: one for HA (CHBr₂) and one for HB (CH₂Br).

  • Chemical Shift: HA is expected to be more deshielded (further downfield) due to being bonded to two electronegative bromine atoms, compared to HB which is bonded to one bromine.

Splitting of HA

• HA is the absorbing proton, and the two HBs are its adjacent neighbors.

• The two adjacent HBs can align their spins relative to the external magnetic field in three ways:

  1. Both HBs align with the field (spin up, up).

  2. Both HBs align against the field (spin down, down).

  3. One HB aligns with and one against the field (spin up, down or down, up – two possibilities).

• These three spin combinations create three slightly different magnetic fields experienced by HA.

• Result: The HA signal splits into a triplet with a characteristic 1:2:1 intensity ratio.

Splitting of HB + Coupling Constant J value

• HBs are the absorbing protons, and HA is the single adjacent neighbor.

• The single adjacent HA can align its spin in two ways: with or against the magnetic field.

• These two spin states create two different magnetic fields experienced by HB.

• Result: The HB signal splits into a doublet with a 1:1 intensity ratio.

• Coupling Constant (J Value):

  • The frequency separation between the peaks within a multiplet (e.g., the two peaks of a doublet or the three peaks of a triplet).

  • If two protons split each other's signals (i.e., they are coupled), they will exhibit the same coupling constant (J). This identity of J values helps confirm which protons are coupled.

Generalizing Splitting Rules (1 and 2)

• Rule 1: Equivalent protons do not split each other's signals.

• Rule 2 (n+1 Rule): To predict the splitting pattern for a specific nucleus:

  • n: Represents the number of non-equivalent adjacent nuclei (protons).

  • Splitting Pattern: The signal will be split into n + 1 peaks.

  • For example, if n=2 (two adjacent non-equivalent protons), the signal will be a triplet (2+1=3). If n=1, it will be a doublet (1+1=2).

Example of characteristic patterns in CH2CH3

• CH₂: Adjacent to 3 hydrogens (from the CH₃ group), so n=3. It splits into a quartet (3+1=4) with a 1:3:3:1 ratio.

• CH₃: Adjacent to 2 hydrogens (from the CH₂ group), so n=2. It splits into a triplet (2+1=3) with a 1:2:1 ratio.

• Characteristic: A quartet coupled to a triplet, with integration values of 2H and 3H respectively.

Example of characteristic patterns in CH2(CH3)2

• Isopropyl Fragment (-CH-(CH₃)₂):

  • CH₃ groups (equivalent): Each CH₃ group is adjacent to 1 hydrogen (from the CH group), so n=1. They split into a doublet (1+1=2). The combined signal integrates to 6H.

  • CH group: Adjacent to 6 hydrogens (from the two equivalent CH₃ groups), so n=6. It splits into a septet (6+1=7). This signal integrates to 1H.

  • Characteristic: A doublet coupled to a septet, with integration values of 6H and 1H respectively.

Complex Splitting patterns (doublet of doublets, splitting by multiple non equivalent neighbors)

• Doublet of Doublets:

  • Occurs when a proton is split by two different sets of non-equivalent protons, and the coupling constants (J values) for these interactions are significantly different.

  • Common in alkenes where cis and trans couplings can differ.

  • Results in four peaks of roughly equal intensity, distinguishable from a quartet by its intensity ratios and distinct J values.

• Splitting by Multiple Non-Equivalent Neighbors:

  • If a proton is split by two or more different types of non-equivalent adjacent protons (e.g., proton B is split by protons A and protons C, where A and C are chemically distinct from each other and from B), the splitting pattern is determined by multiplying the (n+1) factors for each set of neighbors.

  • Formula: (n_A + 1) * (n_C + 1).

  • Example: If proton B is split by 3 protons A and 2 protons C, the total number of lines would be (3+1) (2+1) = 4 3 = 12 lines, forming a complex multiplet.

Splitting patterns- Ex 1: CH₃-CH₂-CO-CH₃

• Molecule A (CH₃-CH₂-CO-CH₃):

  • CH₃ (adjacent to CO): No adjacent hydrogens (n=0). Appears as a singlet.

  • CH₂: Adjacent to 3 hydrogens (from the CH₃ group). n=3. Appears as a quartet.

  • CH₃ (adjacent to CH₂): Adjacent to 2 hydrogens (from the CH₂ group). n=2. Appears as a triplet.

Splitting patterns- Ex 1: CH₂-CH₂-CH₂-CH₂

• Molecule B (e.g., a symmetrical CH₂-CH₂-CH₂-CH₂ system):

  • Outer CH₂ groups (equivalent): Each is adjacent to 2 hydrogens (from the inner CH₂ group). n=2. Appears as a triplet. (Integrates to 4H).

  • Inner CH₂ group: Adjacent to 4 hydrogens (from the two equivalent outer CH₂ groups). n=4. Appears as a quintet (or pentet). (Integrates to 2H).

Proton NMR: Advanced Considerations

• Alcohols (OH Protons)

  • Expected Signals: For a molecule like CH3CH2OH, three distinct signals are expected in proton NMR (CH3, CH2, OH).

  • Observed Splitting:

    • The CH3 protons are split into a triplet by the adjacent CH2.

    • The CH2 protons are commonly observed as a quartet, split only by the CH3, and not by the OH.

    • The OH proton typically appears as a singlet, not split by the adjacent CH2.

  • Rationale for Lack of Splitting: OH (and NH) protons rapidly exchange with other molecules in the sample or solvent. This rapid exchange means the adjacent protons (e.g., on CH2) do not consistently "feel" the magnetic field of the OH proton, thus preventing splitting. This is a common observation, especially in exam scenarios.

• Conformational Changes (Cyclohexane)

  • Axial vs. Equatorial: Cyclohexane has axial and equatorial hydrogens in different chemical environments.

  • Chair Flips: Chair flips rapidly interconvert axial and equatorial positions.

  • Room Temperature Observation: At room temperature, only one signal is observed in the proton NMR spectrum of cyclohexane.

  • Rationale: The chair flip conformational change is faster than the NMR experiment timescale. This rapid interconversion averages the signals from axial and equatorial protons into a single observed signal. Distinguishing them would require cooling the NMR sample.

Carbon-13 NMR

• Purpose: Provides direct information about the carbon skeleton of a molecule, complementing proton NMR data.

• Information Gained:

  • Number of Signals: Indicates the number of different chemical environments for carbon atoms.

  • Chemical Shift: Reveals the electronic environment of each carbon.

• Key Differences from Proton NMR:

  • Natural Abundance: Only about 1% of carbon nuclei are NMR-active Carbon-13 (vs. 99.9% for Proton-1).

  • Signal Intensity & Experiment Time: Lower abundance leads to weaker signals, requiring longer acquisition times.

  • Splitting:

    • Due to low natural abundance, C-C splitting is highly unlikely.

    • C-H splitting is typically suppressed (decoupled) during the experiment, resulting in all carbon signals appearing as singlets.

  • Chemical Shift Range: Much wider (approximately 0-220 ppm) compared to proton NMR (0-12 ppm).

  • Integration: Integration values are generally less reliable in C-13 NMR and do not directly correspond to the number of carbons in a peak.

• Example Application: For a molecule like CH3CH2C(=O)CH2CH3, proton NMR would show two signals (CH3, CH2) with splitting. Carbon-13 NMR would show three signals (CH3, CH2, and the C=O carbon), all as singlets, with the C=O carbon appearing at a highly deshielded chemical shift (e.g., ~200 ppm).

IR Spectroscopy

• Mechanism:

  • Uses infrared (IR) radiation.

  • Absorption of IR photons causes changes in the vibrational motion of molecular bonds.

  • Different bonds vibrate at different energy levels, allowing for functional group identification.

• Units: Energy is reported as wave numbers ((\tilde{\nu})), in inverse centimeters (cm⁻¹), which are proportional to frequency.

IR Spectroscopy: Hooke’s law

• The wave number of a vibration is proportional to (\sqrt{f/m}), where f is the force constant (bond strength) and m is the reduced mass of the atoms in the bond.

• Bond Strength: Stronger bonds (higher f) absorb at higher wave numbers.

• Atomic Mass: Bonds involving lighter atoms (smaller m, e.g., hydrogen) absorb at higher wave numbers.

IR Spectroscopy- Spectrum appearance

• X-axis: Wave numbers (cm⁻¹), typically ranging from 4000 to 400 cm⁻¹, with higher numbers on the left.

• Y-axis: Percent Transmittance (or Transmit). The baseline is at 100% (no absorption), and peaks (absorptions) point downwards towards 0%.

• Peak Characteristics: IR peaks tend to be broad (e.g., OH due to hydrogen bonding) rather than sharp.

IR Spectroscopy: Characteristic Regions- functional group region

• Functional Group Region (1500-4000 cm⁻¹): Most diagnostic for identifying specific functional groups.

  • 4000-2500 cm⁻¹: Bonds to hydrogen (O-H, C-H, N-H). High wave numbers due to the light mass of hydrogen. Different types of C-H bonds (sp, sp2, sp3) can be distinguished by their specific wave numbers.

  • 2500-2000 cm⁻¹: Triple bonds (C≡C, C≡N). Stronger bonds lead to higher wave numbers.

    • IR Inactivity: Symmetrical bonds (e.g., N≡N) are IR inactive because they do not cause a change in the molecule's dipole moment during vibration. An IR active peak requires a change in dipole moment.

    • Intensity: Peak intensity is related to the magnitude of the dipole moment change (e.g., C=O is more intense than C=C due to greater polarity).

  • 2000-1500 cm⁻¹: Double bonds (C=C, C=O).

• Fingerprint Region (400-1500 cm⁻¹): Contains complex absorptions from single bonds and bending vibrations. While rich in information, it's less diagnostic for specific functional groups due to overlapping signals.

UV-Vis Spectroscopy

• Application: Primarily used in biochemistry for analyzing substances like protein concentration.

• Nature: An electronic spectroscopy that examines electronic transitions.

• Transitions: Involves electrons moving from the Highest Occupied Molecular Orbital (HOMO) to the Lowest Unoccupied Molecular Orbital (LUMO).

• Energy: Requires absorption of photon energy to transition from a lower to a higher electronic state.

• Quantification: Can quantify substance concentration using Beer's Law: (A = \epsilon b c), where A is absorbance, (\epsilon) is molar absorptivity, b is path length, and c is concentration.

Mass Spectrometry (MS) -Purpose and process

• Primary Value: Determines the molecular weight and, subsequently, the molecular formula of a compound.

• Process:

  • A sample is introduced into a chamber.

  • It is bombarded with a high-energy electron beam.

  • This process removes an electron, forming a radical cation called the molecular ion (or parent ion).

  • The molecular ion's mass corresponds to the compound's molecular weight.

  • The unstable molecular ion fragments into smaller radicals and cations.

  • The instrument measures the mass-to-charge ratio (m/z) of these fragments.

  • For small molecules, the charge (z) is typically +1, so m/z directly reflects the mass.

MS- Key information (halogen identification and nitrogen rule)

• Molecular Weight: Determined by the molecular ion peak.

• Fragmentation Patterns: Characteristic patterns of fragment ions provide structural clues.

• Halogen Identification (Cl, Br):

  • Chlorine: Exhibits M and M+2 peaks in a 3:1 ratio (due to Cl-35 and Cl-37 isotopes).

  • Bromine: Exhibits M and M+2 peaks in a 1:1 ratio (due to Br-79 and Br-81 isotopes).

  • The M:M+2 ratio helps distinguish between chlorine and bromine.

• Nitrogen Rule:

  • An odd number of nitrogen atoms in a molecule results in an odd molecular ion mass.

  • An even number of nitrogen atoms (or no nitrogen) results in an even molecular ion mass.

• Parent Peak: Corresponds to the molecular ion.

• Base Peak: The most intense peak in the spectrum, often set to 100% relative abundance. It may or may not be the parent peak.

Index of hydrogen deficiency/ degrees of unsaturation

• Purpose: Quantifies the number of pi bonds (double or triple bonds) and/or rings in a molecule.

• Principle: Each pi bond or ring reduces the number of hydrogen atoms by two compared to a fully saturated acyclic alkane.

• Calculation for Hydrocarbons (CnHm): [IHD = \frac{(2n + 2) - m}{2}]

• Adjustments for Heteroatoms:

  • Oxygen (O): Ignore oxygen atoms in the formula.

  • Halogens (X) (group 17): Count each halogen atom as one hydrogen atom.

  • Nitrogen (N): Subtract one hydrogen atom for each nitrogen atom.

  • General Formula (CnHmOxNyXz): Calculate IHD using (C_n H_{(m+z-y)}) in the hydrocarbon formula.

Problem solving strategy for determining chemical structure from graphs

1. Calculate IHD: If the molecular formula is known, calculate the IHD first to understand the number of rings and/or pi bonds. If the molecular formula is unknown, use MS data to deduce it.

2. Analyze IR Data: Identify characteristic functional groups (e.g., C=O, O-H, C≡N, C=C).

3. Analyze NMR Data (Proton NMR):

   • Chemical Shift: Indicates the electronic environment of protons (e.g., aromatic, near electronegative atoms).

   • Integration: Determines the relative number of protons giving rise to each signal.

   • Spin-Spin Splitting (Multiplicity): Reveals the number of adjacent protons, aiding in connecting molecular fragments.

4. Assemble and Verify:

   • Propose a molecular structure that is consistent with all spectroscopic data (IHD, IR, NMR, MS).

   • Ensure the proposed structure matches the molecular formula.

   • Cross-check all data points; for example, if IR suggests a benzene ring, NMR should show characteristic aryl protons.

   • Confirm the proposed structure adheres to basic chemical principles (e.g., correct valencies for all atoms).