unknowns workshop booklet 2014

2008PHM Pharmaceutical Analysis Semester 2, 2014

Unknowns Workshop Booklet: Analysis of unknown organic and pharmaceutical compounds

2

You are analysing a sample of raw material of a drug and found that it contained some residual solvent from the synthesis. Use the spectra below to identify this impurity.

3

Problem 3 1. What is the molecular formula? 2. What functional group/s are present in the IR? 3. UV/Vis: what is the possible chromophore? 4. Mass Spec: What is the parent peak? What are the fragments that give rise to the peaks observed in the spectrum? 5. 1H NMR: Identify the chemical environment of the 1Hs, the integration and the spin-spin splitting (how many neighbouring protons) for the peaks at:

Peak (ppm) Chemical Environment Integration Splitting & n =

1.3

2.0

4.1

6. 13C NMR: Based on the DEPT spectrum and the chemical shift, propose the chemical environment of the carbons at:

Peak (ppm) Chemical Environment 14

21

50

172

Fragment Box

Proposed Structure

4

Unknown organic compound #4

5



0.8

2.1

3.4



28

32

175

Fragment Box

Proposed Structure

6

Unknown Organic Compound #8

7

Problem 8 1. What is the molecular formula? 2. What functional group/s are present in the IR? 3. UV/Vis: what is the possible chromophore? 4. Mass Spec: What is the parent peak? What are the fragments that give rise to the peaks observed in the spectrum? 5. 1H NMR: Identify the chemical environment of the 1Hs, the integration and the spin-spin splitting (how many neighbouring protons) for the peak at:


0.9

N/A



34

Fragment Box

Proposed Structure

8


9



1.9

2.1



38

219

Fragment Box

Proposed Structure

10


11



2.1

5.9



70

Fragment Box

Proposed Structure

12

A medicinal chemist has devised a new synthetic route for a drug that your pharmaceutical company is developing. They send a sample to you to see if you can detect any impurities that may have arisen from this new method. What is the impurity that you have identified from the spectra below?

13



1.2

1.8

4.0

6. 13C NMR: Based on the proton coupled spectrum and the chemical shift, propose the chemical environment of the carbons at:


63

Fragment Box

Proposed Structure

14

Organic Unknown Compound #17

15



2.3

3.5



37

Fragment Box

Proposed Structure

16

You have been analysing a sample of biological fluid. You suspect that your sample contains a neurotransmitter, which you have isolated. You run the spectra below to confirm your suspicions. What is the identity of the neurotransmitter?

17



1.9

2.4

3.0



34

40

Fragment Box

Proposed Structure

18


19



3.5

6.7 & 7.2



114, 120, 130, 160

Fragment Box

Proposed Structure

20

Organic Unknown Compound #23

21



2.6

4.6

7.4



127-142 (4 peaks)

Fragment Box

Proposed Structure

22


23



2.6

7.5 & 7.9

6. 13C NMR: Based on the chemical shift, propose the nature of the carbons at:


~120-140 (4)

188

Fragment Box

Proposed Structure

24


25



3.5

4.5

6.8 & 7.2

7.7



77

~115-130 (4)

158

Fragment Box

Proposed Structure

26


27



1.4

4.0

6.8 & 7.8

6.7 & 7.6

D2O exchangeable

6. 13C NMR: Based on the chemical shift, propose the chemical environment of the carbons at: Peak (ppm) Chemical Environment

12

39

62

~112-160 (4)

169

Fragment Box

Proposed Structure

28

An illicit substance was being analysed for purity by a forensics lab, but was found to have significant

quantities of another compound. A pure sample of contaminating compound was given to you for analysis.

Use the spectra below to identify the unknown substance.

29



0.9

2.1

4.0

6.8 & 7.4

8.0



24

63

~114-155 (4)

170

Address the points below and place your fragments in the fragment box as you go

Fragment Box

Proposed Structure

30

1. Look at the molecular formula This can tell us a great deal of information before we even start: are there any heteroatoms (O,N,S, halogens), therefore what kind of functional groups could be present? It can also tell us about the size of the molecule, and if there are enough carbons for it to be aromatic (> 6 carbons). You can calculate degrees of unsaturation. 2. IR spectrum: what functional groups are present? Use a correlation chart (provided at the back of this workshop), in conjunction with the molecular formula, to identify what functional groups are present. You should easily be able to identify an OH and carbonyl group on sight. 3. UV/Vis Spectrum: is there a chromophore? The UV/Vis will identify whether a chromophore is present. Chromophores arise from conjugation eg. aromatic rings, ketones, aldehydes again, use the molecular formula to identify what is possible. If the molecular formula is > 6 carbons, then it may be due to an aromatic ring, if its < 6 carbons then it may be due to an conjugated alkene, ketone or aldehyde. Also, the chromophore can not be due to an aldehyde or ketone if the formula doesnt contain oxygen. 4. Mass Spectrum: What is the molecular weight/molecular formula and what fragments are present? This is a very powerful technique that can identify important components of the molecule which is produced upon fragmentation. Use a list of common fragments to help identify what may be giving rise to a particular peak, or use a combination of the masses of atoms (H = 1, C = 12, N = 14, O = 16, F = 19, S = 32, Cl = 35, Br = 80) to make up your own (reasonable!) fragment. Always keep in mind the molecular formula when proposing potential fragments to make sure they are possible. Also keep in mind the specific ways that functional groups fragment (eg. alpha cleavage of carbonyls). 5. Proton (1H) NMR: The different chemical environments of the hydrogens This technique will identify how many different chemical environment of 1H there are. There are three very important aspects of 1H NMR: Chemical shift: each chemically distinct proton or group of protons will have a unique chemical shift (where it comes on the x-axis in ppm), depending on the environment it is in, which is very heavily influenced by proximity to electronegative atoms. See Watson Table 8.1 and 8.2 for a useful correlation chart (provided at the back of this workshop). Integration: this is the area under the peak/s and is proportional to the number of protons this peak represents. Keep in mind the molecular formula when calculating the integration, and the number of hydrogens in the formula should be the same as the number of protons identified in the spectrum, unless you have D2O exchange (a proton directly attached to O or N in a solvent of D2O or MeOD. Coupling: This gives information on the number of neighbouring protons (n) using the the n+1 rule. A peak will be split into n+1 peaks due to n number of neighbouring protons, eg. A proton adjacent to a CH3 will be split into n+1 (3+1) = 4 peaks, or a quartet. 6. 13C NMR: The different chemical environments of the carbons Uses the same principles as 1H NMR for chemical shift. See table 8.3 in Watson as a correlation chart. Refer to NMR lecture 3 regarding 1H coupled and decoupled spectra, JMOD and DEPT spectra.

Correlation Charts Common Mass Spec Fragments

31

IR Correlation Charts

33

1H and 13C NMR Correlation Charts

unknowns workshop booklet 2014

Documents

chemical shift

parent peak

dept spectrum

functional groups

possible chromophore

unknown organic compound

molecular formula

fragment box