Fragmentation rules mass spectroscopy

mass fragmentation and its rules

1. PRESENTED BY- SANTHOSH KUMAR T S M.PHARM (PH ANALYSIS) 1 ST YEAR A PRESENTATION ON MASS FRAGMENTATION AND ITS RULES KARNATAKA COLLEGE OF PHARMACY BANGALORE FACILITATED TO- Dr. T SREENIVAS RAO ASSISTANT PROFESSOR DEPT. OF ANALYSIS

2. Mass fragmentation and its rules HIGHLIGHTS

3. Mass fragmentation and its rules

4. Ionizer Sample + _ Mass Analyzer Detector BLOCK DIAGRAM OF MASS SPECTROMETRY

5. General mode of fragmentations: Simple cleavage H o molytic cleavage ( alpha cleavage ) Heterolytic cleavage ( sigma cleavage ) Retro diels alders reaction 2. Rearrangements reactions Mc lafferty rearrangement Elimination reactions

6. ---- HC – C – Z ---- ---- C=C + HZ + Retro Diels-alder + . + . + + . + McLafferty + . .

7. RULES OF FRAGMENTATION 1. Stevensons rule 2. Nitrogen rule 4 . Mclafferty rearrangement 5. Retro diels alder reaction

8. Fragmentation rules in MS Intensity of M . + is Larger for linear chain than for branched compound Intensity of M . + decrease with Increasing M.W. ( fatty acid is an exception ) Cleavage is favored at branching  reflecting the Increased stability of the ion Stability order: CH 3 + < R-CH 2 + < R R CH + < RC + R R R R” CH R’ Loss of Largest Subst. Is most favored

9. Rule 3: Alkanes Cleavage Favored at branching Loss of Largest substituent Favored Rule1: intensity of M . + is smaller with branching Illustration of first 3 rules (large MW)

10. Illustration of first 3 rules (large MW)

11. MW=170 Fragmentation occur at branching: largest fragment loss Branched alkanes

12. Fragmentation rules in MS Aromatic Rings, Double bond, Cyclic structures stabilize M . + and increases the probability of its appearance Double bond favor Allylic Cleavage  Resonance – Stabilized Cation

13. Aromatic ring has stable M .+

14. Cycloalkane ring has stable M .+

15. Fragmentation rules in MS a) Saturated Rings lose a Alkyl Chain (case of branching) Unsaturated Rings  Retro-Diels-Alder + + . + . + . + -R .

16. Fragmentation rules in MS Aromatic Compounds Cleave in b  Resonance Stabilized Tropylium -R . Tropylium ion m/z 91

17. Fragmentation rules in MS C-C Next to Heteroatom cleave leaving the charge on the Heteroatom - [RCH 2 ]  - [R 2 ]  larger

18. Fragmentation rules in MS Cleavage of small neutral molecules (CO 2 , CO, olefins, CN, NH 2 ,SH , H 2 O ….) Result often from rearrangement McLafferty Y  H, R, OH, NR2 Ion Stabilized by resonance - CH 2 =CH 2

19. APPLICATIONS OF MASS SPECTROSCOPY QUALITATIVE ANALYSIS Determination of Molecular weight. Determination of Molecular formula. Determination of Partial molecular formula. Identification of compounds from fragmentation patterns.

20. QUANTITATIVE APPLICATIONS Quantitative analysis of mixtures. Component analysis. Gas analysis. Isotope abundance measurement. Isotope measurement. Component type determination. Thermodynamic studies. Ion molecule reaction. Measurement of ionisation potential. Molecular Structure. Gas chromatograph eluent identification. Impurity detection.

21. Qualitative Applications The mass spectrum of a pure compound provides valuable information of qualitative identification purposes. Components of mixture can also be identified by making use of mass spectroscopy. 1. Molecular weight determination The molecular weight of compound that can be easily volatilized can be calculated easily and the method requires the identification of the molecular ion peak, the mass of which gives the molecular weight to atleast the nearest whole number.

22. The determination of molecular weight, however, suffers from the following difficulties: The molecular ion peak may either be absent or so small that it is confused with a peak caused by an impurity Collision processes may produce M+1 peak that is more intense than the parent ion peak. 2. Determination of Molecular Formula If it is possible to identify the molecular ion peak, the molecular formulae can be determined from the mass spectrum either partially or exactly. By making use of high resolution instrument capable of detecting mass differences of a few thousand of unit, it is possible to derive a unique formula for compound from the exact mass of the ion peak.

23. 3. Determination of Partial Molecular formula If a molecule contains any number of chlorine, bromine, silicon or sulphur atoms, this fact is immediately apparent from the mass spectrum and number of such atoms can be rapidly and accurately deduced. The number of carbon atoms present can also be rapidly estimated to ±1 atom. It is also possible to determine the number of oxygen and nitrogen atoms theoretically but the values obtained are not reliable.

24. 4. Identification of compounds from Fragmentation Patterns Fragmentation of even simple molecules produces a large number of ions with different masses. A complex spectrum is obtained which is very useful for the identification of compound or for the recognition of the presence of functional groups in compounds. A careful study of the fragmentation patterns for pure substances provides useful information regarding rational fragmentation mechanisms and also provides a series of general rules that are helpful in interpretation of the spectra.

25. Quantitative Applications The basic requirements for a successful mass spectrometric analysis are Each component must exhibit atleast one peak that differs markedly from the others. The contribution of each component to a peak, must be linearly additive. The sensitivity must be reproducible to perhaps one percent relative. For calibration, suitable standard must be available.

26. 1. Quantitative analysis of Mixtures In the quantitative analysis of mixture, the spectra are recorded for each component. It should be noted that samples of each compound must be available in a fairly pure state. From a careful inspection of the individual mass spectra, known or suspected to be present in the mixture, it is possible to select analysis peaks on the basis of the intensity and freedom from interference by the presence of both components.

27. 2. Component analysis Large number of compounds, such as natural gas, C 3 -C 5 hydrocarbons, C 6 -C 8 saturated hydrocarbons, C 1 -C 5 alcohols, aldehydes and ketones, C 1 -C 4 chlorides and iodides, fluorocarbons, thiophenes and many others can be analysed without sample heating. Similarly, C 16 -C 27 alcohols, aromatic acids and esters, steroids, fluorinated polyphenyls , aliphatic amides, halogenated aromatic derivatives etc., can be successfully analysed by using higher temperatures. High molecular weight polymeric materials have also been analysed and characterised by Mass Spectroscopy.

28. 3. Gas Analysis If the satisfactory calibration mixtures of known composition are available, almost any type of gas mixture can be analysed quantitatively in the case of simple mixture. Mass spectroscopy has widely been used in the following typical types of gas analysis Monitoring process streams. Synthetic gas mixtures. Atmospheric gases, especially the noble gases, for which it is difficult to find other methods. Monitoring rapid changes in gas composition

29. 4. Isotope abundance measurement Mass spectrometry was originally developed for the study of isotope abundance, and it is also used for the same purpose in recent years. Information regarding the abundance of various isotopes is now employed for a variety of purposes. Some important applications include Determination of formula of organic compounds Analysis by isotopic dilution Tracer studies with isotopes Dating of rocks and minerals by isotopic ratio measurements

30. 5. Isotope measurement Isotopic ratios can be successfully determined accurately by making use of a system in which two collector electrodes are employed to collect the pair of isotopes under test. It should be noted that peaks due to naturally occurring isotopes are present in any mass spectrum, and the highest of the peaks due to an isotope relative to the height of the peak due to the naturally most abundant ion, gives a measure of the abundance.

31. 6. Thermodynamic Studies Mass spectroscopy has also been found to be very useful in thermodynamic studies and can be used over a wide range of temperatures. Heats of vapourisation of high temperature materials can be determined. 7. Measurement of Ionisation Potential Ionisation potential of a molecule is defined as the amount of energy needed to form a molecular ion (i.e. to remove an electron)

32. 8. Molecular Structure The nature of fragments produced in the ion source of a mass spectrometer may be made use of in the study of molecular structure 9. Gas Chromatograph Effluent Identification Complex mixtures can be easily separated by making use of gas chromatograph, but it is not possible with it to identify a component in the effluent stream. It is however, possible to identify each component that is eluted by passing all or some of the effluent into a mass spectrometer.

33. ALL THE BEST THANK YOU

34. REFERENCES www.google.com Instrumental method of chemical analysis – B K SHARMA Principles of instrumental analysis by DONGLAS SKOOG Instrumental method of analysis by CHATWAL