Unless otherwise stated, all images in this file have been reproduced from:

Transcription

1 Unless otherwise stated, all images in this file have been reproduced from: Blackman, Bottle, Schmid, Mocerino and Wille, hemistry, 2007 (John Wiley) ISBN:

2 hemistry 1B EM1002 Lecture 10 Alcohols, (Phenols and Ethers) Alcohols contain the hydroxyl group - bonded to an sp 3 -hybridised 3 r / + 3 onc. 2 S 4 heat r / elimination oxidation Professor Max rossley, oom 514, m.crossley@chem.usyd.edu.au 2

3 Functional Groups Alcohol -ol Propanol Ether -ether Diethyl ether N 2 Amine Amino- or amine Ethylamine N 3 Adrenaline holesterol 3

4 Alcohols Functional Group: (abbreviation ) Electonegativity: > ( ) lone pair of electrons δ+ δ δ+ the low MW alcohols : soluble in 2 higher than expected b.pts. ommon in nature Due to hydrogen bonding 4

5 Structure and properties Alcohols, Phenols and Ethers Ph alcohol phenol ether The oxygen atom of an alcohol, phenol or ether has two lone (non-bonding) pairs of electrons The - bond of alcohols and phenols is strongly polarised with a slight positive charge (δ+) residing on the hydrogen end of the bond and a slight negative charge (δ-) on the oxygen end δ δ 5

6 Alcohols, Phenols and Ethers ydrogen bonding occurs in alcohols (and phenols) in much the same way as in water molecules δ- δ+ δ+ δ- ydrogen bonding (bond strength = kj mol -1 ) Ethers do not show hydrogen bonding and are therefore are not miscible with water. They also have lower boiling points (and m.p.'s) than alcohols of the same MW b.p. 78 b.p

7 Nomenclature ules follow guidelines for hydrocarbons: Find longest carbon chain containing the group Use a prefix to identify the position of the carbon carrying the and a suffix of -ol Use di-, tri- where appropriate If a molecule contains a multiple bond as well as an alcohol, give the carbon with the group the lowest possible number Alcohols may be classified as primary (1º), secondary (2º) or tertiary (3º) depending on whether the carbon atom bearing the alcohol is attached to 1 other carbon group, 2 other carbon groups or 3 other carbon groups, respectively. Give the names of the following alcohols and classify each one as primary, secondary or tertiary ethanol primary alcohol 7

8 Naming Alcohols alkane name - becomes alkanol with a position number if necessary 3 methanol ethanol 1-propanol 2-propanol 1-butanol 2-butanol Find longest chain containing, drop e of alkane & add ol specify - position with the lowest number possible eg, ethyl-1-pentanol 8

9 Alcohols Question Name these 2-butanol 2-methyl-3-pentanol 9

10 1, 2 and 3 Alcohols ' ' '' 1 alcohol 2 alcohol 3 alcohol 1, 2 and 3 indicate the number of groups other than attached directly to the carbon bearing the group 10

11 Alcohols (In complex structures, you will sometimes see the - named as hydroxy and treated like methyl, chloro etc.) 3 2-hydroxypropanoic acid attached to benzene ring: phenols Phenol: 1st antiseptic (carbolic acid) l l l 2,4,6-trichlorophenol: TP 11

12 Acid - Base eactions Many organic reactions are Acid-Base reactions Acids are proton donors Bases are proton acceptors For organic acids - look for - functional groups alcohols + 1 in 1,000,000,000 molecules phenols + 1 in 100,000 carboxylic acids + 1 in 1,000 Note: = 'rest of molecule' 12

13 Acid - Base eactions Difference in acid strength is related to the stability of the anion Alcohols are very weak acids The weaker the acid, the stronger the base required for deprotonation Sodium hydroxide does not react with alcohols: 3 2 Na 2 Na 3 Sodium hydroxide does react with phenols: Na Na Why the difference in reactivity? 13

14 Anion Stability - esonance Stabilisation The phenoxide anion is resonance stabilised The alkoxide anion is not resonance stabilised Therefore phenols are more acidic than alcohols 14

15 Acid - Base eactions Alcohols react with strong base to give the corresponding anion NaN 2 or Na metal + Na + N 3 Na + Na + 2 Na 3 + Na ! Alcohol! Phenol! arboxylic acid NaN 2! Na!Na 3 X X X 15

16 xidation-eduction eactions General considerations first for an organic molecule, Increasing the oxygen content or Decreasing the hydrogen content = oxidation [] content up content down content up 3 [] 2 [] [] Lowest xidation State ighest xidation State emember: Loss of Electrons = oxidation [LE] 16

17 eactions of Alcohols Typical oxidant: high oxidation state transition metal compound e.g. KMn 4, r 3, Na 2 r 2 7 Breathalyser: Na 2 r S 4 orange r Na 2 S 4 green 17

18 Alcohols - xidation eactions The product of oxidation depends on the starting alcohol Treatment with an oxidising reagent (normally Na 2 r 2 7 in dilute acid) results in the oxidation of primary and secondary alcohols Tertiary alcohols can not be oxidised Primary alcohols Primary alcohols are oxidised to give aldehydes, but these are not isolated and further oxidation results in the formation of carboxylic acids r / Not isolated r / Na 2 r 2 7 in aqueous 2 S 4 or K 2 r 2 7 in aqueous 2 S 4 18

19 Secondary alcohols Alcohols - xidation eactions Secondary alcohols are oxidised to give ketones; further oxidation does not occur r / Tertiary alcohols Tertiary alcohols can not be oxidised r / N EATIN 19

20 xidation of Alcohols Primary alcohol aldehyde carboxylic acid 3 r / oxidation 3 r / oxidation 3 primary alcohol aldehyde (not easily isolated) carboxylic acid Secondary alcohol ketone 3 3 secondary alcohol 2 r 2 7 / oxidation 3 3 ketone 20

21 Summary 1. 1 alcohols give aldehydes which then give carboxylic acids r r alcohols give ketones r alcohols do not react r r r 3+ 21

22 Alcohols - Elimination eactions Dehydration requires and on adjacent 's! Alkenes are generally higher in energy than the corresponding alkanes Generally concentrated reagents and elevated temperatures are used oncentrated 2 S 4 is a good dehydrating agent propanol conc. 2 S 4 heat conc. 2 S 4 heat propanol Zaitsev's ule: Where there is a choice, the most substituted alkene forms unsubstituted ethylene monosubstituted alkene disubstituted alkene trisubstituted alkene tetrasubstituted 22 alkene

23 Question Draw the products c. 2 S 4 heat c. 2 S 4 heat c. 2 S 4 heat 23

24 Elimination eactions - Zaitsev's ule The most substituted alkene forms in an elimination reaction 3 2 conc. 2 S 4 heat 3 3 major product minor product Give the major product obtained from the following reaction: conc. 2 S 4 heat 24

25 Mechanism of Dehydration Not for exam Three stages 1. Protonation 2. Loss of water ( S 4 ) oxonium ion carbocation + 3. Deprotonation to form alkene S 4 S

26 Questions Draw the product(s) of the following reactions: r / r / conc. 2 S 4 26

27 Questions Give the reagents required for the following reactions: Na 27

28 Amines Structure sp 3 hybridised nitrogen atom (tetrahedral geometry) N " ' lone pair of electrons in an sp 3 hybridised orbital, ', " =, alkyl, aryl If at least one of the substituents on the nitrogen atom is hydrogen, the amine can form hydrogen bonds Low molecular weight amines are soluble in water δ δ δ N δ N N δ δ δ N hydrogen bonding between molecules of a primary amine hydrogen bonding between an amine and water δ δ N δ δ δ 28

29 Amines - Nomenclature Amines may be classified as primary (1º), secondary (2º) or tertiary (3º) when there are one, two or three substituents attached to nitrogen, respectively When there are four substituents attached to the nitrogen, the nitrogen atom must bear a positive charge and is called a quaternary (4º) ammonium salt For simple amines, the suffix -amine is added to the alkyl substituent Use di, tri-as appropriate lassify the following amines as primary, secondary, tertiary or quaternary N 2 ethylamine (primary amine) N diethylamine N triethylamine N 2 N Br cyclohexylamine tetramethylammoniumbromide 29

30 Amines - eactions Amines are weak organic bases (proton acceptors) N N Amines are nucleophiles and react with alkyl halides in a nucleophilic substitution reaction 3 3 N 3 3 I 3 3 N 3 3 I 30

31 Biologically Important Amines Many biologically active compounds contain the amine functional group N 3 quinine - antimalarial 3 N 3 codeine - analgesic 3 N cocaine 3 3 N 3 N 3 N-methylamphetamine (speed) MDMA (ecstasy) 3 31

32 hirality (+)-limonene odour in oranges (-)-limonene odour in lemons 32

33 Back to the Isomer Tree Isomers same molecular formula onstitutional Isomers Different nature/sequence of bonds Stereoisomers Different arrangement of groups in space onformational Isomers Differ by rotation about a single bond onfigurational Isomers Interconversion requires breaking bonds Enantiomers Non-superposable mirror images Diastereoisomers Not mirror images 33

34 Flashback L3 Stereoisomers Isomers which differ in arrangement of groups in space (same nature and sequence of bonding) Two groups: onformational isomers (conformers) differ by rotation about a single (-) bond not normally separable at room temperature onfigurational isomers Interconverted only by breaking and remaking bonds. This process normally requires considerable energy so does not happen at room temperature 34

35 Isomers and stereochemistry - ecap Examples of onstitutional isomers 1-butene 2-butene butane 2-methylpropane Example of onformational isomers eclipsed staggered Better described As Diastereomers Examples of onfigurational isomers 3 3 (Z) and (E) alkenes 3 cis- trans- 35 3

36 Flashback L3 Diastereoisomerism in Alkenes igher priority groups on the same side of double bond alkene is denoted (Z) igher priority groups on opposite sides of double bond alkene is denoted (E) Br 3 l (Z)- 2-butene higher priority groups on same side (E)- 2-butene higher priority groups on opposite sides (E)-1-bromo-2-chloropropene higher priority groups on opposite sides 36

37 Flashback Isomerism Isomers same molecular formula onstitutional Isomers Different nature/sequence of bonds Stereoisomers Different arrangement of groups in space onformational Isomers Differ by rotation about a single bond onfigurational Isomers Interconversion requires breaking bonds Enantiomers Non-superposable mirror images Diastereoisomers Not mirror images 37

38 hiral molecules (optical isomers) Stereochemistry - Enantiomers A molecule is chiral if it is not superimposable upon its mirror image A pair of molecules which are not identical but are mirror images of each other are called enantiomers Almost all of the physical and chemical properties of a pair of enantiomers are identical (melting point, boiling point, solubility etc.) A chiral molecule contains a stereogenic centre (also known as a stereocentre or chiral centre) A stereogenic centre is a tetrahedral sp 3 hybridised carbon atom with four different groups attached to it In these molecules there is no plane of symmetry

39 Stereochemistry - Achiral molecules Achiral molecules are any molecules that do not contain a stereogenic centre mirror plane nly 3 different groups are attached to the tetrahedral carbon. This moelcule therefore has a plane of symmetry. Question: Are the following molecules chiral or achiral? F l Br F l Br Br 39

40 Mirror Images Enantiomers are mirror images of each other and are NT Superposable (cannot be superimposed on each other) Blackman, Figure

41 Molecules in Nature We live in an asymmetric world! The two enantiomers behave identically when reacting with an achiral reagent (one without stereogenic centres) But they often react in different ways towards another chiral compound 41

42 Taste and Smell ur smell and taste receptors are chiral and differentiate between enantiomers Question: Spot the Stereocentres limonene odour in oranges odour in lemons 2 N 2 N asparagine N 2 N 2 bitter sweet 42

43 hiral Molecules - Pharmaceuticals Pharmaceuticals are often sold as a mixture of the two enantiomers: ibuprofen There have been cases in which the two enantiomers have very different effects in the body: N thalidomide N N N mild sedative extreme teratogen 43

44 ptical Activity ow can we distinguish enantiomers in the lab? The physical properties of a pair of enantiomers are identical with the exception of their interaction with plane polarised light Plane polarised light consists of waves oscillating in only one plane All chiral compounds (enantiomers) rotate the plane of polarised light to some extent - this is why they are called optically active. We use an instrument called a polarimeter to measure the sign and magnitude of the rotation. These values can not be predicted by looking at the structure - they must be determined experimentally A sample of one enantiomer rotates plane polarised light in a clockwise direction, the other enantiomer rotates the light with the same magnitude but in the opposite direction (+)-limonene odor in oranges (-)-limonene odor in lemons 44

45 Polarimeter Blackman, Figure

46 Isomers - practice questions Determine what sort of isomers the following pairs of molecules are (Note - they may also be identical compounds rather than isomers): l l l l

47 Absolute onfiguration The absolute configuration of a stereogenic centre refers to the exact three dimensional arrangement of the groups l l Br F Br F l Br F Br F l F Br l F Br l These all have the same absolute stereochemistry - they are just different representations of the same enantiomer

48 Nomenclature ow do we describe different enantiomers? It is important to know which of the 2 possible isomers of a chiral compound you are working with We use the ()- and (S)- descriptors to name different enantiomers This is known as the absolute configuration of a compound and refers to the exact arrangement of atoms in 3D space stereogenic centre of one possible configuration mirror plane stereogenic centre of one possible configuration l l F Br Br F This enantiomer is designated as (S)- This enantiomer is designated as ()-

49 The rules for ()- and (S)- Describing Absolute onfiguration Identify the stereogenic centre Assign the 4 groups attached in order of priority (higher atomic number = higher priority) rient the molecule so that the lowest priority group is at the back For remaining 3 groups see if priority 1,2 and 3 are ordered in a clockwise or anticlockwise fashion lockwise = ()- ; anticlockwise = (S)- mirror plane l l F Br Br F

50 Describing Absolute onfiguration (continued...) Assigning priority If two (or more) atoms attached directly to the stereogenic centre are the same, move down the chain to the next atoms and compare their atomic numbers 2 Br 3 F Multiple bonds are expanded to give the same number of single bonds to that atom F is considered to be F

51 Describing Absolute onfiguration (continued...) Assign the configurations of the following stereogenic centres: l

52 ptical Activity ow do we distinguish enantiomers in the lab? Physical properties of an enantiomeric pair are identical except for one: their interaction with plane polarised light Plane polarised light consists of waves oscillating in only one plane unpolarised light polariser plane polarised light light source

53 Polarimeter When plane polarised light is passed through a solution of one pure enantiomer, the plane of polarisation is rotated The enantiomer is said to be optically active The amount of rotation (α) is characteristic of the enantiomer α polariser analyser observer light source

54 ptical otation ne enantiomer causes clockwise rotation, other enantiomer rotates the light an equal amount in the opposite direction otation in a clockwise direction is labelled (+), anti-clockwise rotation as (-) It is not possible to predict which enantiomer is (+) and which (-) without performing the experiment acemic mixtures give an overall rotation of zero (+)-limonene odour in oranges (-)-limonene odour in lemons