Structure Determination How can the structure of an unknown compound be determined? Before modern analytical tools were developed (for organic chemists this means the development of NMR (~1950s) or IR (first used ~1900, not readily obtained until mid 1900s), the only experimental evidence for the identity of an organic compound was elemental analysis A chemist could thus determine the % of various elements in an unknown sample For example, if a sample had 1 part carbon and 4 parts hydrogen (CH4) what is the constitution? H H H C H H H C H H How to test the possible structures? 1 Structure Determination In order to distinguish the possible constitutional isomers, experimentalists would react the compound in a substitution reaction and detect the number of isomeric products H H Cl H C H H C Cl H C H Obtain 1 isomer H H H Same compound H Cl H H H C H H C Cl H C Obtain isomers H H H Different compounds By reacting methane in a variety of reactions, it was determined that a monosubstitution always produced only 1 isomer, therefore all 4 hydrogens must be equivalent 2 Structure Determination In addition to the constitution, however, what was the configuration? How are the 4 equivalent hydrogens arranged in space? H H H C H H C H C H H H H H H Planar Pyramidal Tetrahedral H H H C Cl H C H C H H Cl Cl H H Each possible configuration would generate only 1 isomer with monosubstitution (thus the 4 hydrogens are at equivalent positions) React twice By logic, eventually a Cl H tetrahedral geometry Cl was proposed H C Cl Cl C Cl H C H Cl C H Cl Cl H Cl C H H H Cl H Two products Two products One product! 3 Structure Determination This was the state of affairs until the beginning of the 20th century, for any new compound the elemental analysis was obtained and then the structure was inferred by systematically running reactions or by comparing to analogous compounds Could a model be developed to predict the structure of organic compounds? In 1916 G.N. Lewis published a paper that hypothesized that bonding occurred by sharing electron pairs between atoms (in contrast to ionic bonds) We now call these structures “Lewis dot structures” by explicitly designating all valence electrons as a dot Only designate H B C N O F valence electrons The constitution could thus be predicted by filling the outer shell of electrons for each atom (second row atoms thus need 8 electrons and thus an octet rule) H O H Two electrons shared “resonance” Filled outer shell for all atoms 4 Structure Determination Original course notes from Lewis (1902) The cube indicated does not indicate easily how multiple bonds are formed, or what is the angle between various bonds C C C C ??? The Lewis dot structures work well to determine the constitution of a molecule (atoms are bonded in a way that allows a filled octet rule to form), but does not indicate configuration 5 Structure Determination The intuitive arguments of Lewis to determine constitution by sharing electrons to form a filled outer shell, however, were given mathematical basis by Heitler and London (1927) Studied binding energy of H2 molecule H H Figure from Heitler and If electron 1 was only London* associated with hydrogen 1 and electron 2 was only associated with hydrogen 2 H1 e1 H2 e2 If electron constraint was Calculated bond energy a removed and each electron fraction of actual can interact equally with both nuclei e1 H1 e H2 2 Energetic basis for a “bond” Calculated bond energy much -sharing of electrons between two atoms closer to actual *W. Heitler, F.Z. London, Z. Physik, 1927, (44), 455-472 6 Valence Bond Theory The intuitive description proposed by Lewis where bonds are formed between two atoms by sharing valence electrons in order to obtain a filled octet for the outer shell is basis of “Valence Bond Theory” This theory is still the underlying principle most organic chemists use to rationalize chemical reactions and predict chemical properties Two major results from valence bond theory: 1) Concept of Resonance Resonance structures result from electrons being associated with different nuclei For H-H molecule e1 e1 H1 e1 H2 e2 H1 e2 H2 e1 H1 H2 H1 H2 e2 e2 ΨMOL = c1 Ψ1 + c2 Ψ2 + c3 Ψ3 + c4 Ψ4 Actual structure is a combination of all contributing structures with appropriate weighting factors Called “principle of linear combination” 7 Resonance in Organic Compounds What is resonance? (also called ‘delocalization’) Look at a nitro group O RNO2 R N O The negative charge on the oxygen could be placed on either oxygen using Lewis structures O O R N R N O O Which structure is correct? It turns out neither structure is correct, but the charge is delocalized onto both oxygens -This process of being able to delocalize the charge onto more than one atom is called resonance (Resonance is a result of not being able to draw an accurate structure using one Lewis structure) 8 Resonance in Organic Compounds “Rules” of Resonance 1. All resonance structures must be valid Lewis structures (e.g. cannot have 10 electrons on one carbon in one structure) 2. Only electrons move (cannot move nuclei, only electrons – usually double bonds or lone pairs connected through an extended p orbital system) 3. Number of unpaired electrons must be constant 9 Resonance in Organic Compounds Concept of resonance allows explanation of a number of chemical properties How does resonance explain acidity? Consider pKa of organic molecules pKa CH3CH2OH CH3CH2O H 16 O O H3C H3C H 4.8 OH O Resonates similar to nitro group Both structures place a negative charge on oxygen after loss of proton, but the pKa difference is greater than 11 10 Resonance in Organic Compounds A carbonyl group is a common resonance source O -H O O H3C H3C H3C O H O O Once the acid is deprotonated, the negative charge is located on one oxygen The charge can be delocalized (resonated) onto the other oxygen Neither structure is correct, but rather the negative charge can be delocalized over both oxygen atoms Resonance structures are simply a result of one Lewis structure being incomplete in describing the location of electrons A double headed arrow always means two (or more) resonance forms Two arrows mean two chemically distinct structures 11 Resonance in Organic Compounds Comparison of Electron Density for Ethoxide versus Acetate anion O O O CH3CH2OH CH3CH2O H3C H3C H3C OH O O The excess negative charge is more stable on the acetate anion that can resonate, thus the conjugate acid is more acidic 12 Resonance in Organic Compounds Resonance also allows explanation for the concept of electronegativity Electrons in a chemical bond need not be shared equally between two nuclei For H-Cl molecule e1 e1 H e1 Cl e2 H e2 Cl e1 H Cl H Cl e2 e2 ΨMOL = c1 Ψ1 + c2 Ψ2 + c3 Ψ3 + c4 Ψ4 Unlike with H2 where the Ψ1 and Ψ2 wavefunctions were more stable than the charged wave functions, with HCl the Ψ4 wave function is the most stable, therefore highest coefficient The electrons are more stable closer to Cl than H, therefore the chlorine atom is said to be more “electronegative” than the hydrogen atom These resonance considerations therefore also cause bond dipoles in unsymmetrical bonds 13 Electronegativity Tables Linus Pauling first established values to associate with each element (there have been many different values computed, but the trend is the same) Elements toward the upper right hand of the periodic table are more electronegative Also can predict the relative electronegativity of two atoms by their relative placement in the periodic table H (2.3) Li (0.9) Be (1.6) B (2.1) C (2.5) N (3.1) O (3.6) F (4.2) Cl (2.9) H3C OH Br (2.7) 2.5 3.6 I (2.4) The numbers are a relative indication of how much the electrons are ‘attracted’ to a certain atom As the number becomes larger, the electrons are attracted more by that atom 14 Resonance in Organic Compounds The bond dipoles resulting from unsymmetrical bonds also can affect the acidity O O pKa H 4.8 H3C OH H3C O O O H 0.7 Cl3C OH Cl3C O Anion with trichloroacetic acetate is stabilized by inductive effects from polarized C-Cl bonds O Cl C O Cl Cl 15 Induction Induction refers to electron movement “through bonds” -All bonds between different atoms are polar and the electrons are closer to the more electronegative atom “on time average” As the electronegative atom is further removed, the inductive effect is less (inductive stabilization is through bonds, therefore if there are more bonds to transverse the effect is less) O O F Base F OH O H H H H X pKa The electronegative H 4.8 fluorine pulls electron I 3.2 density away from F 2.6 carboxylate 16 Field Effect Can have similar effect merely through space (field) rather than through bonds (inductive) H Cl Cl H H Cl Cl H CO2H CO2H Which is more acidic? H Cl Cl H H Cl Cl H CO2 CO2 17 Resonance in Organic Compounds Important to Remember: Not all resonance structures need to contribute equally If two resonance structures are not of equal energy, then they will not contribute equally to the actual structure H H H H N N H H H H Octet rule obeyed Positive charge on on all atoms less electronegative atom This leads to major and minor contributors 18 Resonance Forms H H H H N N H H H H Deeper blue color on carbon (less charge on carbon) Actual “hybrid” structure 19 Resonance Forms O O O O H C CH H3C CH3 H3C CH3 H3C CH3 3 3 major minor inconsequential Only a resonance form if spins are paired Not all resonance forms need to contribute equally, but rather a weighting factor is given to each resonance form depending upon its importance to the actual form Typically forms with more bonds are more important (often due to forms