Structure Determination How to determine what compound that you have? One way to determine compound is to get an elemental analysis -basically burn the compound to determine %C, %H, %O, etc. from these percentages can determine the molecular formula Still need to determine structure from molecular formula We have learned various isomers can result from a given molecular formula Consider O O OH C3H6O H Could have a Different type No carbonyl ketone of carbonyl present If we only know the molecular formula, would not know which structure is present Structure Determination Even if a pure sample is obtained, how do we know the actual structure of the compound? The development and improvement of analytical instruments to determine structure has been one of the biggest advancements in organic chemistry during the past 60 years Today almost any structure can be determined with these instruments The important part is to recognize what information each instrument provides, and if deciding between possible isomers which technique can be used to differentiate Techniques to be learned: Mass Spectrometry UV-vis Spectroscopy IR Spectroscopy NMR Spectroscopy -mass of compound -conjugation present -functional groups -bond connectivity of -isotopes present structure -distinguish some atoms -symmetry -most important for structure determination Mass Spectrometry Can determine the molecular weight of a sample and some information about the structure A key part of a mass spectrometry is the need to create a charged species The most common method to create the charged species is electron impact ionization e H H H H H H e H C C C H H C C C H e H H H H H H An electron is accelerated toward a gaseous sample of the compound under consideration Due to the high energy of the electron moving at high speed, an electron is expelled The sample thus is now positively charged, due to the loss of one electron, and is a radical/cation structure Mass Spectrometry The compound (R) thus becomes a radical/cation when bombarded with electrons magnet e R(•+) detector R The radical/cation continues along a path until it reaches a magnetic field Charged species become deflected (are attracted to one magnet) in the presence of the magnetic field and hence the path direction is bent The radius of curvature is dependent upon the mass of the species (m/z), lighter mass species are deflected more and heavier species are deflected less Only a certain mass can thus deflect the correct amount with the curvature of the instrument, heavier species will hit one wall while lighter species will hit the other wall The magnet strength is changed and depending upon when species hit the detector the mass of the compound can be determined Mass Spectrometry The parent ion is called the molecular ion peak (M+) m/z 72 Can find molecular ion, but what are the other peaks? Mass Spectrometry The molecular ion peak can fragment Due to the high energy of the radical/cation generated, this species can fragment CH3CH2 m/z 72 m/z 43 CH3 m/z 57 Remember only the charged species will be detected (the radical species will not be affected by the magnetic field) The probability of obtaining a given fragment is due to the STABILITY of the cations produced Effect of Isotopes Remember that an isotope has the same number of protons and electrons, but a different number of neutrons Since neutrons and protons are the “heavy” parts of an atom, the extra number of neutrons will cause a greater mass In a mass spectrometer we can see the effect of this by peaks above the molecular ion peak (M, M+1, M+2, etc.) The ratio of these peaks is diagnostic for which atoms are present The natural abundance of isotopes is well known M M+1 M+2 H 100% C 98.9% 1.1% S 95% 0.8% 4.2% Cl 75.5% 24.5% Br 50.5% 49.5% I 100% Effect of Isotopes Can distinguish atoms by the ratio of peaks above the molecular ion Especially useful to distinguish which halogen is present Cl Br I m/z 78 m/z 122 m/z 170 M/M+2 = 3 M/M+2 = 1 M/M+2~ 3/1 = 1 Mass Spectrometry Nitrogen Nitrogen is also diagnostic in a mass spectrum due to the odd/even parity of the mass Consider small molecules and their corresponding mass CH4 m/z = 16 NH3 m/z = 17 The molecular ion peak for a molecule with one nitrogen is always odd, all other common atoms in an organic compound yield an even mass Fragmentation Behavior of Common Functional Groups Alkenes With an alkene the common fragmentation is to create an allylic carbocation m/z 70 m/z 55 Alcohols Two common effects 1) Loss of water OH H2O m/z 74 m/z 56 Alcohols 2) α-cleavage OH OH OH CH2CH3 m/z 74 m/z 45 McLafferty Rearrangement Any ketone containing a γ-hydrogen can rearrange to the enol form in a MS H H O O m/z 100 m/z 58 Ketones Ketones can also do α-cleavage similar to alcohols O O O CH2CH2CH2CH3 m/z 100 m/z 43 High Resolution Mass Spectrometry (HRMS) These high sensitivity mass spectrometers, called HRMS, can be used to determine molecular formula a HRMS can detect particle masses with an accuracy of 1/20,000 therefore > 0.0001 amu (atomic mass units) Can use this to distinguish compounds with a similar rough mass but with a different molecular formula 12C 12.0000 amu (by definition) 1H 1.0078 amu 16O 15.9949 amu Many structures may have the same integer value molecular weight, but different molecular formulas For example: O HN NH C4H6O1 C5H10 C3H6N2 70.0418 amu 70.0783 amu 70.0531 amu Structure Determination Using Spectroscopy Need methods to distinguish between possible structures A nondestructive way is to use absorption spectroscopy In a simplified picture: Beam splitter Monochromatic sample detector light source blank The ability of the sample to absorb incident radiation is measured by the difference in absorbance at the detector versus the blank Electromagnetic Spectrum All light travels at a constant speed The difference is the wavelength of the light (which also determines the energy of the light) E = hν = (hc) / λ NMR IR UV-vis Infrared Region Wavelength of infrared radiation is ~800 cm-1 to 4000 cm-1 wavenumbers (wavenumbers correspond to number of wavelengths of light in 1 cm) -common descriptor for IR frequencies by organic chemists As the wavenumber becomes larger the energy increases The energy level of infrared light corresponds to the energy required to cause molecular vibrations Depending upon what type of bond is present determines the exact energy required to cause the vibration The energy of light absorbed therefore indicates what functional group is present Bond Vibration The energy of the infrared light can interact with the resonant vibrational frequency of the bond Since different bonds have different energies, they require different energy to cause vibration consider acetone O O E H3C CH3 H3C CH3 The carbonyl has a strong dipole When electric field aligns with dipole, bond shortens The absorption of the infrared light thus changes the dipole for this bond as it vibrates Infrared Spectroscopy Active versus Inactive IR only causes a vibration if there is a change in dipole during vibration Therefore symmetric bonds are inactive CH3-CH3 the carbon-carbon bond of ethane will not observe an IR stretch Or any other symmetric bond An IR “active” bond is therefore a bond that changes dipole during vibration, While an IR “inactive” bond is a symmetric bond that doesn’t change dipole during vibration Number of Vibrations The number of possible vibrations for a given molecule is determined by the number of atoms present For nonlinear molecules obtain 3N-6 vibrations (N equals number of atoms present) 3N-5 vibrations for linear molecule For example consider acetone again (C3H6O1) Acetone has 10 atoms and is nonlinear Therefore expect 3(10)-6 = 24 vibrations The other vibrations are due to different bonds besides the carbonyl stretching, for example the hydrogens Or bending motions Intensity of Absorbance Intensity of light absorbed by a molecule is related to the dipole of the bond The greater the dipole, the greater the absorbance intensity C-O bond stretches are therefore more intense than C-C stretches O C O Realize the intensity of absorbance is not related to the wavenumber The wavenumber is related to the force constant for the bond vibrating (the stiffness of the bond) Infrared Spectroscopy Factors to be considered in an IR spectrum 1) Position of absorbance (wavenumber) Energy required for absorbance 2) Intensity of absorbance Related to the dipole of the bond 3) Shape of absorbance (broad or sharp peaks) Tells information about the type of bond Infrared Spectroscopy Specific functional groups As mentioned specific functional groups have characteristic absorbance frequencies Consider carbon-carbon bonds Wavenumber (cm-1) C C ~1200 cm-1 C C ~1660 cm-1 C C ~2200 cm-1 As the number of bonds increases between two atoms, the stiffness of the bond increases which results in a harder bond to stretch Infrared Spectroscopy Conjugation lowers the stretching frequency (RESONANCE!!!) Wavenumber (cm-1) ~1640-1680 cm-1 ~1620-1640 cm-1 Whenever a functional group becomes more conjugated (adjacent to double bonds for example) the stretching frequency lowers Infrared Spectroscopy C-H bond stretching As the %s character increases in a bond, the bond becomes stiffer (already saw that sp hybridized C-C bonds are stiffer than sp3 hybridized C-C bonds) Same is true for carbon-hydrogen bonds sp3 hybridized 2800-3000 cm-1 sp2 hybridized 3000-3100 cm-1 sp hybridized ~3300 cm-1 Key point: only sp3 hybridized C-H bond stretches are below 3000 cm-1 Infrared Spectroscopy Alcohols and amines Both O-H and N-H bonds are “stiff” bonds