IR Spectroscopy: Pharmaceutical Chemistry (PDF)

PL1001 Pharmaceutical Chemistry Organic Spectroscopy; an introduction Dr Lynda Storey N548 RSE [email protected]  Introduction Last time we covered: – Electromagnetic spectrum – Ultraviolet and Visible Spectroscopy Today we cover: – Infrared Spe...

PL1001 Pharmaceutical Chemistry Organic Spectroscopy; an introduction Dr Lynda Storey N548 RSE [email protected]  Introduction Last time we covered: – Electromagnetic spectrum – Ultraviolet and Visible Spectroscopy Today we cover: – Infrared Spectroscopy  Ultraviolet (UV) and Visible (VIS) Spectroscopy This is when E.M. radiation in the 180-400 nm (UV) and 400-780 nm (VIS) interacts with molecules. Absorption of this energy causes an excitation of an electron from a bonding to an antibonding Excited states molecular LUMO orbital: Lone pairs of electrons HOMO Ground states  Learning Objectives Understand the origin of the IR spectrum at the molecular level Explain the appearance of an IR spectrum Use various areas of the IR spectrum in structure determination Show an awareness of the various methods of sample preparation  Pharmaceutical Applications of IR Qualitative fingerprint check for identity of raw materials used in manufacture and for identifying drugs Provides a way of identifying functional groups within a molecule Can analyse samples in solid and semi- solid states e.g. creams and tablets  Infrared Spectroscopy The transition of an electron between different energy levels is called an electronic transition – Occurs in absorption and fluorescence (UV-Vis & fluorescence) Molecules exhibit two additional types of radiation-induced transitions – Vibrational and rotational transitions – These vibrational energy levels are stacked within each electronic level Vibrational energy of a molecule is associated with the bonds that hold the molecule together – These are set values and only assume certain discrete levels The energy required to bring about these vibrations is small and is achieved using electromagnetic radiation in the infrared (IR) region. It involves stretching & bending of bonds.  Infrared Spectroscopy IR spectra are absorption spectra. This radiation has just enough energy to bring about a bond stretch or bend. The spectrum that is produced is plotted as wavenumber (cm-1), i.e. reciprocal of wavelength. IR radiation is of lower energy than UV bending stretching etching & Bending Vibration Mod Symmetrical Asymmetrical Bend Stretch Stretch To absorb infrared radiation, the bond must be polarisable: -Only asymmetrical vibrations absorb IR light. Fully symmetrical molecules do not display absorbance in the IR region (e.g. O2, N2,etc.). UNLESS asymmetric stretching or bending is possible (i.e. a dipole can be induced).  More than one way to vibrate Each different vibration/ bend results from a different frequency of radiation. O O O H H H H H H Anti-symmetric Symmetric More than one option for stretching 3756 cm-1 Bending 1595 cm-1 stretching 3652 cm-1 complicated compounds. O C O O C O O C O Anti-symmetric Symmetric Produces lots of bands in IR stretching 2349 cm-1 O C O stretching 1388 cm-1 spectrum. Bending (degenerate) H H H H H H H H 667 cm-1 Normal modes of vibration in water C C C C and carbon dioxide Br Cl Br Cl Br Cl Br Cl Deformation Rock Wag Twist Modes of Vibration in bromochloromethane, H2CBrCl  Group Frequencies In general the absorption frequency depends on: – the mass of the atoms bonded (bowling ball verses tennis ball) – The strength of the bond (Steel ruler verses plastic) One absorption band can appear in the spectrum at the same frequency for many molecules Group Frequencies Use tables of group frequencies (correlation charts) for interpretation of IR spectra – Also use databases of IR spectra for identifying unknown compounds  How does the mass of the atom affect the absorption frequency? C-H C-D C-O C-Cl 3000 2200 1100 700 absorption cm-1 The lighter the atom the higher the frequency of absorption. How does the bond strength affect the absorption frequency? C C C C C C 2143 1715 1100 absorption cm-1 The stronger the bond the higher the frequency.  Regions of the IR spectrum Increasing energy required to vibrate bond bond strength bond to triple double single hydrogen bonds bonds bonds so light, hard to get stretch O H C C C C C O going N H C F C N C O C Cl C H 4000 3000 2000 1500 1000 frequency scale in wavenumbers  What you would expect to see in a vacuum bands O-H CC C=C Finger print Region N-H C=N single bonds CN C-H C=O C-O C-F C-Cl etc.  IR Spectrum The complexity of the spectrum between 1500 – 400 cm-1 makes it difficult to assign all the absorption bands Due to the unique patterns found here it is called the fingerprint region The area between 4000 – 1500 cm-1 are usually due to stretching vibrations of diatomic units and sometimes called the group frequency region bsorptions for bonds to hydro Bond IR frequency Bond strength, kJ mol–1 C-H 2900-3200 440 N-H 3300-3400 450 O-H 3500-3600 500 From this table we can predict: O-H bond requires more energy to make stretch than N-H O-H bond stronger than N-H, stronger than C-H  Ph= H H H H H sp2 hybridized  Analysis of Different Samples Liquid films – Drop of liquid spread between 2 IR plates (not suitable for volatiles) Solutions – Must select appropriate solvent based on solubility of sample – Background correction using blank solvent  Analysis of Different Solids Samples – Ground solid to a paste and add mulling agent (nujol – an oil) – Paste is then placed between 2 IR plates – Or, mix sample with dry KBr in a mortar then subject to high pressure in an evacuated die to produce transparent disc Gases – Since densities are much less than liquids, need longer pathlengths  British Pharmocopoeia In order to prove a drug is what it should be, the BP has IR spectra of standard compounds The IR spectra of an unknown must match EXACTLY with that from the BP – Includes all peaks and relative intensities  British Pharmocopoeia The fact functional groups give absorptions at particular frequencies can be used to determine the purity of a compound Contamination from solvent residues or by- products will show absorptions not observed in a pure compound Possible to distinguish the same compound marketed by a number of different manufacturers – Spectra will be slightly different  Summary IR is longer wavelength than UV = lower energy IR spectroscopy involves vibrational energy of bonds in the molecule Specific bonds have specific frequencies Used to determine functional groups in a structure Able to help determine the structure of an unknown compound using IR spectroscopy Also has the ability to analyse any form of sample – Solid, liquid or gas  Points to consider from today’s lecture What is the difference between the energy levels used in UV-Vis and IR? What information can you get from IR? What type of samples can be analysed by IR and by what methods? Which functional groups will give an IR absorption and why?