Structure determination

Molecules with what spin quantum number can be observed by NMR?

any number that is not 0 or an integer; odd number of nucleons

In the presence of an applied magnetic field, how many orientations can nuclei with I ≠ 0 have?

2I + 1

What are the energy states of nuclear spins a) aligned and b) opposed to an applied magnetic field?

a) α; low energy

b) β; high energy

How is an NMR spectrum obtained? (4 steps)

1. a broad range of frequencies are applied to the sample as a pulse

2. some α energy state nuclei excited to higher energy

3. free induction decay: the excited α state nuclei return to ground state

4. The free induction decay is transformed mathematically into a spectrum

frequency that promotes nuclear spins from α to β of an individual nucleus

Larmor frequency: v = γ B₀/2π

• γ: gyromagnetic ratio unique to nucleus

• B₀: magnetic field strength

Greater electron cloud shielding (decreases/increases) the effect of the NMR magnetic field on the nucleus, making the shift appear more (down/up)field.

Greater electron cloud shielding (decreases/increases) the effect of the NMR magnetic field on the nucleus, making the shift appear more (down/up)field.

*upfield= right

What are the compounds used as reference in NMR?

TMS for organic/non-polar solvents

TSP for polar solvents

Double bond equivalents formula

C+1 - (H+X)/2 + N/2

How do signals for a) CH₃, b) CH₂, c) CH, d) CR₄ appear in DEPT spectrum?

a) positive

b) negative

c) positive

d) doesn’t appear in DEPT, only proton decoupled

How is chemical shift (δ; ppm) calculated from frequency for where to appear in the HNMR spectrum?

δ = v_sample - v_{reference /} v_reference

v is in Hz

Equation that relates chemical shift and frequency

δ (ppm) = v_shift (Hz) / v_spectrometer (MHz)

What are the two most significant types of coupling?

What is the ²J for a) sp³ and b) sp² centers?

a) 20 to 6 Hz

b) 2 Hz

TRUE OR FALSE: All Hydrogens couple to each other

FALSE: identical hydrogens do not couple, ie. hydrogens that are in interchangeable positions

What is ³J for sp³ centers?

0 to 16 Hz

Karplus relation

J = J_0/180 cos² Φ - c

Where Φ is the dihedral angle between ³J coupled H:

• 0° ≤ Φ ≤ 90° ≤ Φ ≤ 180

What are common couplings for a) cyclohexanes and b) cyclopentanes?

a) 2-6 Hz

b) 4-13 Hz

What is the Coupling constant of a) H to H and b) H to H?

a) 3-12 Hz

b) 10-20 Hz

a) Which coupling constants would a more electronegative group X affect and b) how?

a) ³J

b) a more electronegative group lowers J

a) Is ³J_cis of ³J_trans more strongly dependent on ring size of cyclic structures and b) what effect does increasing ring size have?

a) cis

b) increase in J

Substitution of a heteroatom in an aromatic system leads to (no change/decrease/increase) in J_ortho across the adjacent bond.

Substitution of a heteroatom in an aromatic system leads to (no change/decrease/increase) in J_ortho across the adjacent bond.

⁴J couplings are in what Hz range?

1-3 Hz

For an A₂X₃ system what would be a) the multiplicity of signals and b) the intensity (combined heights of all peaks)?

a) A₂: quartet, X₃: triplet

b) A₂: 2/3, X₃: 3/3

The same reasoning applies to all other combinations of AX and AMX

Nuclei are chemically equivalent if…

they are in the same chemical environment / are related by an operation of symmetry

What makes an ABX system hard to analyse? (2)

• signal intensities are not 1:1

• chemical shift is not at center of signals

Nuclei are magnetically equivalent if…

they are chemically equivalent and are equally coupled to neighboring nuclei

TRUE OR FALSE: Nuclei are magnetically inequivalent if they are not chemically equivalent but are equally coupled to neighboring nuclei

FALSE: if they ARE chemically equivalent but AREN’T equally coupled to neighboring nuclei

TRUE OR FALSE: in an AMX system, A is more closely related to M than X

TRUE: letter closer in the alphabet indicate shifts/frequencies closer together

What is a a) weakly and b) strongly coupled system and c) which is first order analysis applicable to?

a) Δv/J >5

b) Δv/J <5

c) a

When is first order analysis valid for coupled spin systems (eg. AMX)?

When it is a strongly coupled system ie. all Δv/J (eg. (v_M - v_A)/J_AM) >5

Nuclei in a region of high electron density experience a (__) magnetic field than those in a region of low electron density, and so they come into resonance (__) at (__) ppm.

Nuclei in a region of high electron density experience a weaker magnetic field than those in a region of low electron density, and so they come into resonance upfield at low ppm.

Substitution of hydrogen by an alkyl group causes what kind of shift in a) the carbon and b) attached hydrogens?

a & b) downfield (because more electronegative)

In cyclohexane, are equatorial or axial hydrogens more deshielded?

equatorial

Which hydrogen will be at higher/lower ppm and why?

H will be at lower ppm than H because H is shielded by anisotropy of the pi bond

For the following molecules, rank the a) hydrogens and b) carbons from highest ppm (most deshielded) to lowest.

a) H > H > H > H

b) C > C > C > C > C

Do aromatic carbons and hydrogens have a) greater or lower shifts than non-aromatic, and b) how does increasing rings size affect this feature?

a) greater

b) increases

TRUE OR FALSE: Mass spectrometry relies on ions being in the gas phase

TRUE

What is a shortcoming(s) of mass spectrometry?

not useful for involatile sample that can’t be turned into a gas, or for high MW or heat sensitive compounds

How is mass spectrometry conducted? (3 steps)

1. ionization: generates cations (some cases anions) in gas phase

2. ion separation: Separates mixtures of gas phase ions according to their mass to charge ratio (m/z)

3. ion detection: detects abundance which is reflected in generated spectrum

TRUE OR FALSE: only radicals are seen by mass spectrometry

FALSE: They are not seen because they are not charged. Only cations (M⁺) and radical cations (M⁺˙) show up

What are the types of electrons that can be lost during ionisation to give a radical, from most likely to least likely

lone pair > π > σ

Identify the molecules that give rise to the following M with significant M+2 peaks

What is the relationship between m/z and N in the compound?

Even m/z = even (or 0) number of N

Odd m/z = odd number of N

*if containing only C, H, N, O, S or Halogen

Simple cleavage: C-C bond cleavage

The most stable cation (tertiary > secondary > primary) will be formed preferentially

Is simple cleavage C-X bond cleavage or C-C more likely to occur in the same molecule?

C-X because the bond is weaker than for C-C

Simple cleavage: allylic/ benzylic β-cleavage

the cation is resonance stabilized

Simple cleavage: α-cleavage

homolytic breaking of the carbon-carbon bond adjacent to a functional group containing a heteroatom

Retro Diels Alder rearrangement

McLafferty rearrangement

Proximity (Ortho) rearrangement

Easy way to recognize the presence of an alcohol in the MS spectrum?

loss of H₂O (m/z 18)

IR characteristic peaks (12)

3500-3200: R-OH

3400-3100: R_x-NH

3350-3175: CH (alkyne)

3200-2500: carboxylic acid

3175-3000: CH (aromatic)

3000-2800: CH (alkane)

2900-2700: aldehyde

2400-2200: nitrile

2300-2100: CC (alkyne)

1750-1650: C=O

1650-1550: C=C (alkene)

1625-1500: R-NH₂

¹H NMR shifts (10)

13.0-10.0: carboxylic acid

10.5-9.5: aldehyde

8.5-6.0: aromatic

8.5-5.5: amide

7.0-4.5: phenol

5.5-4.5: vinylic

4.0-3.2: H-CO

4.0-3.0: H-C-X

2.8-2.0: H-C-C=O

2.5-1: H-C (sp³)

¹³C NMR shifts (9)

220-160: C=O

155-100: C=C, C_(sp)N

90-65: alkyne, C-NO₂

75-50: C-O

<60: C-X

<50: C-H (sp³)