Week 1 Introduction to Organic Chemistry Lecture Notes PDF

Week 1 Part 1. Introduction to Organic Chemistry  CH3 Li O F Prof. David Lupton Me Me Room 238 in Building 23S...

Week 1 Part 1. Introduction to Organic Chemistry  CH3 Li O F Prof. David Lupton Me Me Room 238 in Building 23S CO2Me TMSO https://users.monash.edu/~d CO2Me wlupton/index.html Strategy? Weeks 1 and 2 Reaction Discovery? OHC CHO O H H 3C H O HO H CH3 CH3 CH3 VID Pre-workshop activity recap Organic chemistry is the chemistry of carbon containing compounds. 1. Their structures. 2. Their properties. 3. Their reactions. Organic compounds are very common and comprise materials with the elements shown. VID You are organic chemistry 98% of the atoms in your body are O, C, N or H FOOD STIMULANTS AND MEDICINES O CH3 O H 3C N NH H OH N S CH3 H R O O H N N CH3 HO N O N HO OH O N CH3 CO2H H OH H H H O NH2 N O N N O O OH H 3C P O CN OH oleic acid O H 3C O CH3 OH O  VID Your world is full of organic Hchemistry O C 3 H CH3 N hexane H 3C CH3 N heptane H O H 3C CH3 indigo octane and many others... Fuel OH OH O HO O F F F F F F HO O O OH OH n Cellulose (paper) F F F F F F F F teflon Expectations for CHM1022: Weekly tasks Workshop Read workbook and watch all online content Complete the preparation quiz for the coming week Attempt your worksheet prior to the workshop Engage with the workshop Laboratory Complete your pre-lab exercise as per the schedule Submit your laboratory report as per the schedule Learning objectives for Week 1 1.Understand the relationship between carbon hybridization and structure. 2.Identify and appreciate the difference between conformational isomers and alkene stereoisomers. 3.Assign the stereochemistry of alkenes. 4.Understand the differences between nucleophiles and electrophiles. 5.Appreciate the two steps in reaction of alkenes with acids  How do we draw organic molecules? Molecular formula: Molecular formula tells you the ratio of atoms. C21H30O2 Structural formula shows how the atoms are connected. Many types of structural drawing are used in chemistry, for example: A vertex is a “C” atom. In this case with two bonds to other “C” atoms. H H H Therefore 2 hydrogens C CH3 CH3 that are not drawn. H H C C H H C C O H 2C CH OH OH H H H H C C C H H 2C C C H C C C H H H H C C CH H H H2 H2 H H C C C C C C H 3C C C C C C H 3 C H H O C C C C H O C C C CH3 O CH3 C H CH3 H H2 H2 CH 3 H H H H H H H H H Line Bond Structural Drawing Condensed Structural Drawing Skeletal Structural Drawing (also called condensed line drawing) How many bonds are draw to this ”C”? How many hydrogens are needed? WORK How do we describe the structure of organic molecules? 1. The hydrocarbon scaffold is a mixture of alkane, alkene, alkyne and arene. 2. Most organic compounds have multiple functional groups attached. 3. They have a 3-dimensional structure.. HASHED BOND. Into page CH3 Alcohol. Oxygen with one carbon and one OH BOLD BOND. Out of H hydrogen page H H 3C O CH3 CH3 Ether. Oxygen with two carbons attached Classes of hydrocarbons Alkane bonding Alkanes are molecules with 2 sp3 hybridized carbons making a s-bond. They have the formula CnH2n+2 and can be described as saturated. As all bonds to carbon involve sp3 hybridised orbitals all substituents are 109○ to each other. 109○ H H H H H C C CH3 H C C CH3 H 3C H H 3C H Sigma (s) bond. sp3 orbital. Alkanes are in motion O N F N O O NH O All molecules are constantly in motion. Rotating about bonds, twisting, vibrating. A stable orientation of a molecule is called a conformations. “Consider the top ring of linozelid….it is folded over so that it comes out of the binding pocket” Week 1 Part 2. Alkenes Learning objectives for Week 1 1.Understand the relationship between carbon hybridization and structure. 2.Identify and appreciate the difference between conformational isomers and alkene stereoisomers. 3.Assign the stereochemistry of alkenes. 4.Understand the differences between nucleophiles and electrophiles. 5.Appreciate the two steps in reaction of alkenes with acids  Alkene bonding Alkenes are molecules with 2 sp2 hybridised carbons making a carbon carbon p-bond and s-bond. They have the formula CnH2n and can be described as unsaturated. Pi (p) bond P orbital H CH3 H CH3 C C C C H 3C H H 3C H sp2 orbital Sigma (s) bond Alkene bonding Alkenes are molecules with 2 adjacent sp2 hybridised carbons making a carbon carbon p-bond. The presence of the p-bond results in all substituents residing in the same plane. The C-sp2 hybridisation means each substituent is 120○ from the next. H CH3 C C 120○ H 3C H 90○ Alkene isomerism Changing between cis and trans retinol requires energy (in the previous example from light). Rotating about an alkene Rotating about an alkane (C=C) (C-C) H H C C H H This is a small amount of energy. ~264 kJ mol-1 H H The two H C conformations H C H rapidly interconvert. H H H ~13 kJ mol-1 H H H H H H C C C C C H C H H C H C H H H H H H H H  Types of isomerism Are they Isomers? Different compounds with same molecular formula. Are they Constitutional Isomers? Are they Stereoisomers? Different order of attachment of atoms Same order of attachment, different position of atoms in space Conformational isomers? Enantiomers? Diastereoisomers? Interconvert rotation of s-bond Mirror images of each other All other stereoisomers Are your hands the same? (more on this in week 6) Alkenes isomerism is diastereoisomerism. They are described as trans (or E) and cis (or Z) Synthesis What is Chemistry? A science that deals with the composition, structure, and properties of substances and with the transformations that they undergo. A central aspect of organic (and inorganic) chemistry (i.e. CHM1022) is chemical synthesis. O catalytic H 2SO 4 O H 3C OH H 2O CH3 H 3C O CH3 Butyric acid Ethanol Ethyl butyrate 1c per mL 2c per mL 200c per mL Smell of vomit Smell of pineapple  H 1022 Organic Synthesis Summary R R REDUCTION R R alkene H alkane ADDITION Note: “R” indicates a X X OH hydrocarbon or hydrogen. R of H2O of HX R R R R or R or X2 H H X alcohol alkyl halide dihalide O R R OXIDATION WEEK 1: Alkenes O R esters OH O O O R R R SUBSTITUTION HO OXn H R carboxylic O acid aldehyde ketone R R R NH2 N ADDITION ADDITION H amides OH OH WEEK 4: Carbonyls WEEK 5: Esters and Amides R R R R H R alcohol alcohol Summary of CHM1022 Organic Synthesis REDUCTION, ADDITION, OXIDATION AND SUBSTITUTION describes the type of reaction occurring. Most definitions are as you would imagine. ADDITION: adding an atom or group of atoms to a molecule. SUBSTITUTION: exchanging an atom or group of atoms from a molecule. OXIDATION: The loss of electrons (or hydrogen atoms) from a molecule. REDUCTION: The gain of electrons (or hydrogen atoms) from a molecule. Addition of HCl to an Alkene Alkenes react with strong acids by ADDITION of the two atoms of the acid. It converts an alkene to a halogenated alkane. H Cl H CH3 CH3 H 3C H-Cl H 3C H H H Alkene Strong acid Halogenated alkane Addition of HCl to an Alkene The proton has no electrons and reacts with electron-rich molecules to gain electrons. -The proton is described as being electrophilic (definition: something that likes electrons) Strong acid dissociates readily H Cl H CH3 CH3 H 3C H Cl H 3C H H H -The alkene is described as being nucleophilic (definition: something that likes nuclei) H H H CH3 C C H C C CH3 H 3C H H 3C H Addition of HCl to an Alkene The reaction occurs in two steps and proceeds via one intermediate. Step 1: The proton (electrophile) reacts with the alkene (nucleophile). Step 2: The carbocationic intermediate (electrophile) which reacts with the chloride (nucleophile). H H Cl Cl Step 1 Step 2 H CH3 CH3 CH3 H 3C H Cl H 3C H 3C H H H H H H Intermediate in square brackets. H Often unstable, but sometimes can be isolated. C C CH3 H 3C H  Energy profile of HCl addition to alkenes Intermediate at a local energy minima. H Cl Energy CH3 H 3C H H Cl H H CH3 CH3 H 3C H 3C H Cl H H H Step 1 Step 2 Reaction course Addition of HCl and Markovnikov’s rule When both ends of the alkene have different numbers of hydrogens two products can be formed: H H Cl H H CH3 CH3 CH3 H-Cl or H Cl In 1891 Markovnikov proposed the following rule: "Addition of H-X to an alkene occurs such that the carbon with the most gains more." Addition of HCl and carbocation stability Markovnikov’s rule is a consequence of the inherent stability of carbocations. H H H CH3 H CH3 H 3C CH3 C C C C H H CH3 CH3 methyl cation primary cation secondary cation tertiary cation Left to Right: Increasing in stability Addition of HCl and Markovnikov’s rule H Cl H Cl H CH3 CH3 or H H H Cl H H CH3 CH3 CH3 H-Cl or H Cl In 1891 Markovnikov proposed the following rule: "Addition of H-X to an alkene occurs such that the carbon with the most gains more." Electrophiles and nucleophiles Many organic reactions are described as being polar and involve a nucleophile and electrophile reacting. make a new bond they are driven by the electrostatic attraction of the electrophile and the to nucleophile. A nucleophilic species is either an atom with a lone pair of electrons or a p-bond Examples H2 H 2C C H H 3C O N CH3 lone pair lone pair π-bond An electrophile is either an atom with a vacant orbital or a polarised bond Examples CH3 H2 δ H 3C CH3 δ C H C C H 3C O O CH3 H CH3 vacant s-orbital vacant p-orbital polarised O-H bond polarised O-C bond  Summary In Week 1 we have: Distinguished between conformational isomers of alkanes and alkene stereoisomerism. Assigned stereochemistry of alkenes. Introduced multistep reactions with alkenes. Defined nucleophiles and electrophiles. Discussed Markovnikov’s rule and carbocation stability.