topic 2: properties of molecules (organics)

up to lecture 6, pg 32

The chemicals of life 

Living systems use and produce a wide range of chemicals 

• Simple chemicals like water,carbon dioxide, salt 

• Highly complex molecules like proteins, nucleic acids and other natural products 

The majority are organic compound 

• Historically, organic compounds were thought to be only produced by living organisms, but Wöhler’s generation of urea from inorganic components showed that production of organic compounds doesn’t need a ‘vital force’ 

•  It’s now well established that even non-natural organic molecules can be prepared synthetically 

Organic compounds 

• Molecules based on carbon covalently bonded to other elements – esp hydrogen, oxygen, and nitrogen 

• Carbon is able to form strong covalent bonds to a wide range of other elements, and link to a wide number of other atoms (carbon has 4 bonding regions) 

• Huge number of combinations of molecules are available: over 16 million organic compounds are known

Representing organic molecules 

• Name (systematic) 

• Common name 

• Molecular formula 

• Condensed structuralformula 

• Lewis structure 

• Full structural formula 

 Skeletal structures (aka stick/line diagrams) 

• Skeletal structures are the most efficient way to draw complex organic molecules 

• The hydrocarbon framework is shown as a series of lines 

• Clearly show functional groups (where reactions happen) 

• Functional groups may be drawn with non-bonding electron pairs (aka lonepairs) shown - optional 

Include non-bonding electrons if they are important for consideration of molecular shape or reaction mechanism, otherwise it’s up to you! 

drawing skeletal structures 

• The end of each line represents a carbon, unless a heteroatom is specified 

• Hydrogens on carbons are implied but not usually drawn, so as to make a neutral molecule with filled octets on each carbon, unless a charge or unpaired electron is shown 

• Hydrogens on functional groups must be included  

• Double and triple bonds are shown by two or three parallel lines 

• Bond angles in hydrocarbon frameworks are drawn roughly consistent with tetrahedral, trigonal planar and linear shapes 

abbreviations in skeletal structures

Me: methyl

Et: ethyl

iPr: isopropyl

tBu: tertairy- butyl

Ph: phenyl

CHO: aldehyde

CO2H: carboxylic acid

Skeletal structures and functional groups 

• Functional groups may be drawn with non- bonding electron pairs shown (or not) 

• include non-bonding electrons if important for consideration of shape or mechanism 

Functional Groups – Reactivity and Characterisation 

• Reactions occur primarily at functional groups, including biochemical reactions 

• Certain reactions are characteristic of particular functional groups 

Functional groups can be distinguished by spectroscopy: 

• infrared (IR) 

• Nuclear magnetic resonance (NMR) 

• Ultraviolet/visible (UV/vis) 

Functional groups can be distinguished by mass spectrometry

Identifying Carbonyl Functional Groups with IR spectroscopy

• The C=O bond of carbonyl and carboxyl functional groups has a stretching vibration in the region of 1800 – 1650 cm-1. 

• The exact wave number depends on what other groups are attached, i.e. which type of carbonyl/carboxyl FG it is. 

Isomers 

• Non-identical compounds with the same molecular formula are isomers 

• isomers typically exhibit different properties (physically, chemically and/or biologically) 

• Different functional groups react differently 

• Different order of atom connectivity leads to different shapes and physical natures – e.g. “packing” of  molecules in a solid or liquid affects melting point or boiling point, respectively=regioisomers 

• Different spatial arrangements of atoms lead to different 3D shapes 

The presence of different isomers is isomerism 

Classes of isomerism 

Isomerism 

• Same number and types of atoms 

Structural isomers 

• Different order of attachemen of atoms 

• Postitional/chain isomers 

• Fucntional group isomers 

Stereoisomers 

• Same order of attachment of atoms, different orientation 

• Confirmational isomers 

• Configurational isomers 

stereoisomerism 

Isomers that have the same order of connectivity of atoms but different spatial arrangements 

• Further divided into: 

Conformational isomers 

• differ in the spatial arrangement of groups around single bonds; usually interconvert rapidly 

Configurational isomers  

• differ in the spatial orientation around a cycloalkane, an alkene or a chiral centre; don’t interconvert readily 

• cis-/trans-, E-/Z-, R-/S-isomers 

• chirality = handedness 

Wedge and dashboard stereoboards 

• wedge: gets fatter towards us.  

• Hash: gets fatter away from us 

Representing 3d spatial arrangement on 2d plane 

cycloalkanes - stereoisomerism

Same connectivity, different three dimensional forms 

• Configurational isomers 

• Different arrangement about cycloalkane ring(different faces) 

• Named as cis- (same face) and trans- (opposite faces) 

alkenes - stereoisomerism

Same connectivity, different three dimensional forms 

• Configurational isomers 

• Different arrangements across double bond (different sides) 

• Named as cis- (or Z-) and trans- (or E-) 

naming Typically uses longest chain, if group cis to longest chain: is cis and vice versa.  

Ambigious method however, need better way 

CIP method of naming stereoisomers 

a robust naming system for stereoisomers 

• uses the atomic number to define the priority of each substituent 

• describes the relative spatial positions of the substituents systematically 

Step 1: Rank the atom directly attached to each carbon of interest based on atomic number 

• Highest atomic number is highest priority 

• Lowest atomic number is lowest priority 

Step 2: If atoms are the same, look at their substituents and rank the next atoms out 

• Calculate based on the first point of difference 

Step 3: For an alkene, compare the relative spatial positions of the highest ranked substituents at each end of the alkene 

• If the highest ranked substituents at each end are on the same face (cis), then it is a Z-alkene (Z-name) 

• If the highest ranked substituents at each end are on the opposite faces (trans), then it is an E-alkene (E-name) 

 

Z- or E- goes at the start of the name. If there is more than one alkene, put a number in front to denote which position the alkene starts at

Retinal stereoisomers 

• Double bonds cannot rotate 

• But in certain cases where high levels of conjugation (lots of double bonds in a row), can rotate between z- and e- forms 

• Eg rentinal stereoisomers change conformation/rotate in presence of light 

• Change in shape leads to impulse that causes vision 

Chirality 

Same connectivity, different three dimensional forms 

• Configurational isomers 

• Different spatial arrangements (configurations) around one or more carbon atoms 

• Most chiral molecules contain at least one chiral centre. 

• A carbon atom with FOUR DIFFERENT substituents attached is a chiral centre 

• A molecule with one or more chiral centres will usually exist as non-superimposable mirror image isomers (enantiomers) 

There are only two possible ways to arrange the substituents around a single chiral centre. 

The two are never superimposable = ENANTIOMERS 

enantiomers

Non-superimposable mirror image isomers are called enantiomers 

• A molecule with chiral centres has two enantiomeric forms in which the sense of chirality at the chiral centres is reversed 

• Enantiomers have identical atom connectivity and functional groups and differ only in the spatial orientation of the groups around a chiral centre 

• Enantiomers behave identically except in the presence of other chiral agents (chiral molecules; plane polarised light) 

 As biological molecules (e.g. proteins, nucleic acids) are chiral molecules, enantiomers often behave differently in the human body and other life forms 

Enantiomers and optical rotations 

Plane polarised light is a chiral environment (generated in a polarimeter) 

• A chiral molecule will make the light rotate either clockwise or anticlockwise: optical activity 

• A chiral molecule that rotates plane polarised light clockwise is dextrorotary (D), denoted (+) 

• its enantiomer rotates plane polarized light anticlockwise, is levorotatory (L), denoted (-)  

(From Latin dextra for right and laevus for left.) 

Racemic mixtures 

A 50:50 mix of enantiomers is called a “racemic mixture” or “racemate” 

Racemates can have different chemical properties from the individual enantiomers 

• Eg Racemates can have lower melting points, as pack less tightly compared to individual enantiomers

Naming stereoisomers: CIP rules 

Step 1: Rank the atom directly attached to each carbon of interest based on atomic number 

• Highest atomic number is highest priority (=1) 

• Lowest atomic number is lowest priority (=4) 

Step 2: If atoms are the same, look at their substituents and rank the next atoms out 

• Calculate based on the first point of difference 

 Step 3: If substituent contains double or triple bonds 

• Represent each multiple bond as single bond linkages to 2 or 3 different atoms of the same type 

• Ghost atoms are the 2nd and 3rd (for an alkyne) linkages and they are only attached  to the original partner; the real atom at the other end is treated as having a ghost version of the original partner 

Step 4: For a chiral centre, compare the relative spatial positions of the three highest ranked substituents in order, with the lowest priority substituent at the back 

• If the first to third highest ranked substituents are arranged in a clockwise manner, then the chiral centre is named R- 

• if the first to third highest ranked substituents are arranged in an anti-clockwise 

• manner, then the chiral centre is named S- 

enantiomer naming

1. Assign CIP priorities 

2. Make sure the lowest priority substituent is pointing “back” 

3. Ignoring the lowest priority substituent, determine direction 

4. R is clockwise number ordering, S is anti-clockwise 

Diastereoisomers 

• A molecule with more than one chiral centre has stereoisomeric forms in which the sense of chirality at some BUT NOT ALL OF the chiral centres is reversed: diastereoisomers (= diastereomers) 

• Diastereomers are not mirror image isomers 

• Diastereomers behave differently in the presence or absence of other chiral entities: they are different chemical entities 

• A molecule with two chiral centres usually has two enantiomeric forms (both chiral centres inverted), each of which has a diastereoisomeric form (four stereoisomers in total) 

Conformational isomers 

• Different 3D arrangements of atoms resulting from rotation around a single (σ) bond: conformational isomerism 

• Conformational isomers are also known as conformers 

• Interconversion is fast and continuous at normal temperatures 

• Can’t distinguish conformers based on bulk properties of the compound 

Protein conformation 

Protein conformation affect activity 

Kinase-ATP  

• conformations in cell  signalling 

Serotonin transporter  

• conformation for neural signalling 

Tau protein  

• conformation key to Alzheimer’s disease 

Reactivity

Why do reactions happen? What factors are important for reactivity? 

Bond stability (unstable/weak bond is more reactive) 

Electrons (valency and lone pairs) 

Bond motion (eg stretching, vibration)  -

• High energy means more stretch, breaks easily  

• Bond polarity 

Thermodynamics 

• Enthalpy (overall stability of all bonds in molecular entity compared between starting molecule and product) 

• Entropy (increased disorder, universe has tendency to move towards more disorder) 

• Changing conditions/environment 

Electronegativity 

measure of the ability of an atom in a molecule to attract electrons to itself 

• Increases across a row (lef to right) 

• Increases up a group (bottom to top) 

 Bonds between carbon-hydrogen are relatively unpolarised, share electrons evenly. Therefore, many organic molecules are based off them.  

bond polarity 

• A bond between two different elements with be polarised (since every element has different polarity) 

Ionic bonds: 

• Form between atoms with very different electronegativities (eg NaCl) 

Non-polar covalent bonds 

• Occur between identical atoms (H2) 

Polar covalent bonds 

• Occur between non-identical atoms with similar electronegativities (eg HF) 

In a polar covalent bonds, the more electronegative partner has a greater attraction for the bonding electrons 

• The electron density of the bond is greater closer to the more electronegative atom 

• δ+ means an atom has a partial positive charge on it 

• δ- means an atom has a partial negative charge on it 

• Dipole arrow shows the direction of electron polarisation (the cross is at the more positive end) 

Molecular dipoles 

Compounds with polarised bonds may or may not be polar, depending on symmetry (in a symmetrical molecule, bond polarities cancel out) 

Organic molecules with carbon chains and one (polar) functional group have a molecular dipole generally orientated towards the functional group

reaction mechanisms 

• A reaction mechanism shows a step-by-step picture of the way a reaction occurs 

• It breaks the reaction progress down into elementary steps 

A mechanism includes a description of: 

• how reactants interact 

• which bond(s) break(s) 

• which bond(s) form(s) 

• any intermediates formed 

• the order and timing of the steps 

Organic chemical reactions that occur in one step are concerted reactions (elementary reactions) 

• Concerted=all happens at same time 

Organic chemical reactions that occur in several steps are stepwise reactions (complex reactions) 

Studying reaction mechanism allow you to: 

• Predict the structure of products from new reactions 

• Understand/rationalise the outcome of a reaction 

• Predict the effect of changing the reaction conditions on the outcome of a reaction 

Reaction mechanisms are studied experimentally by kinetics and theoretically by computational methods 

Curly arrow 

• Curly arrows are a pictorial way to show mechanism in organic chemistry reactions 

• Chemists use curly arrows to show movement of electrons and, thus, bond formation and cleavage 

• In organic chemistry, used to show and work out mechanism of reaction 

full arrow head: motion of two electrons

hald arrow head: motion of one electron

base goes from nucleophile/lewis base (where electron comes from)

head goes to electrophile/lewis acid (where electrons go to)

nucleophile vs electrophile and heterolytic vs homolytic

Nucleophile=donate electron to form bond (base) 

Electrophile=receive electron to form bond (acid) 

Heterolytic: 2 electron movement

homolytic: 1 electron movement, creates radicals (not assessed)

curly arrow and heterolytic bond cleavage 

• Curly arrows show the motion of two electrons 

• Heterolytic cleavage is the breaking of a bond in an unsymmetrical fashion, leaving a negative charge at the atom that the electrons move to and a positive charge at the other end 

How to draw curly arrows: 

• In heterolytic cleavage the arrow goes from the bond (where the two electrons are) to the more electronegative atom 

• Orignally bond is sharing electrons, br takes electrons when seperating, causes C to be positive 

Curly arrow goes from bond towards more electronegative element 

curly arrow and Heterolytic bond formation 

• Heterolytic bond formation is the forming of a bond in an unsymmetrical fashion 

• The curly arrow points from an anion towards a cation OR from an electron rich centre towards an electron deficient one 

How to draw curly arrows: 

• In heterolytic bond formation, the curly arrow should point to where the new bond forms (which is where the electrons end up) 

• But sometimes it is clearer to have it pointing to the electrophile itself 

Curly arrows: heterolytic processes 

1. Drawing lone pair, then curly arrow from lone pair to hydroxide of acid, then another curly arro from bond to O  

2. Do same for second reaction 

Overall, draw curly arrow from broken bond to electronegative atom bonded to, then another curly arrow from reactant to now free atom that will bind 

curly arrows and resonance 

• Resonance is movement of electrons within a molecule or ionic system 

• Resonance is used when a single Lewis structure isn’t sufficient to show the bonding situation 

• Resonance is a stabilising effect (electron density and/or charge is spread over more area/atoms) 

• Resonance occurs through π-bonds and lone pairs 

Resonance stabilization of charged intermediates: 

Carboxylate: from lone pair towards double bond, then from double bond to electronegative atom 

benzylic cation: stabilisation of the cation by movement of positive charge due to defiency of electron spread over 7 atoms/carbons 

allylic cation: pi electrons donate e- to form resonance structures

Curly arrows and mechanism 

• A simple acid dissociation demonstrates the use of curly arrows in showing reaction mechanisms

• The mechanism of dissolution of hydrogen chloride (a strong acid) in water to form the hydroxonium ion can be shown using curly arrows: 

• Curly arrows are meant to show only electron motion, not molecular motion 

• We therefore draw the reactants ca. one bond length from each other 

lewis structure and mechanism 

• A reactant with a lone pair may donate it to form a new bond to an atom with a (partial) positive charge 

• Sharing electrons leads to a positive charge on the atom with the lone pair 

• The remaining lone pair on the product is not available for reaction because the positive charge deactivates it 

• When an electronegative atom or group cleaves from a neutral reactant (with the electrons of the bond), it becomes negatively charged 

• This is because it has gained an electron from the bond that it originally shared 

Classes of reactions: 

Substitution 

• Group substituted for another 

Addition 

• Group added 

Elimination 

• Group removed 

Redox 

• Acid/base