Theme 6 and 7 Carbonyl Compounds & Carbohydrates

Theme 6 and 7 Carbonyl Compounds & Carbohydrates R C Aldehyde Smith: rganic Chemistry Extracts from Chapters 19, 20, 21, 22 and 27 C 2 Sucrose R C Ketone R' C R R' Ester R C Carboxylic acid C R N Amide 1

The Carbonyl Group C ybridisation Bond angles Geometry Bond Polarity The δ+ Carbon will be attacked by nucleophiles The lone pair e- on the xygen can be protonated by a strong acid 2

A. Carbohydrates Carbon and water formula C n ( 2 ) n Simple carbohydrates Monosaccharides e.g. glucose and fructose Disaccharides e.g. sucrose and lactose Complex carbohydrates - Polysaccharides For structure cellulose and lignin For storage starch and glycogen Glycoproteins = carbohydrate linked to protein Glycolipids = carbohydrate linked to lipid 3

Monosaccharides Contain 3 7 carbons, formula C n 2n n Possess a C= group and all other carbons are bonded to groups, except if specifically stated otherwise, eg. 2-deoxyribose aldehyde C C C aldose = sugar with aldehyde FG ketone C C C ketose = sugar with ketone FG C3 = triose, C4 = tetrose, C5 = pentose, C6 = hexose 4

Combining the names gives: an Aldotriose e.g. glyceraldehyde a Ketotriose e.g. dihydroxyacetone steroisomers an Aldohexose e.g. glucose a Ketohexose e.g. fructose C C C C C C 2 stereoisomers C 2 C C C C C 2 stereoisomers 5

Representing Stereochemistry Every carbohydrate except dihydroxyacetone contains 1 or more stereocentres, so will have optically active stereoisomers Fischer Projections are a standard way of representing the stereochemistry of sugars Vertical lines point into the page (away from you) orizontal lines point out of the page (towards you) C s at centre are omitted C C = C 2 = C 2 s and their bonds on centre C s may be omitted. Monosaccharides are written with the carbon backbone vertical and the C= nearest the top 6

Convert the following Fischer projections into line structures with stereochemistry and assign the absolute configuration of the stereocentres: C C C 3 2 N C C 3 C 3 C 2 C 3 7

D and L Sugars In D sugars the on the penultimate carbon is on the right hand side and in L sugars it is on the left hand side. The terms D and L come from glyceraldehyde where the D is dextrorotatory and the L is levorotatory BUT D and L do not predict the sign of optical rotation because they refer to only one of many stereocentres. Classify the following monosaccharides for type of C=, no of C s and D or L C C 2 C 2 C 2 C 2 An aldohexose has 4 stereocentres, so 16 stereoisomers. alf of 8 these are D-sugars and half are L-sugars. C 2

Fig 27.4 Configurations of D-aldoses * Memorise * * * * * * 9 All altruists gladly make gum in gallon tanks! *

Isomerism D-glucose and L-glucose are enantiomers. C C 2 L-glucose D-glucose D-mannose L- Epimers differ in configuration at only 1 stereocentre D-glucose and D-mannose are epimeric at C2 D-glucose and are epimeric at C4 D-glucose and L- are epimeric at C5 C 2 C 2 D-fructose Are epimers enantiomers or diastereomers? What is the relationship between D-fructose and D-glucose? Are D-glucose and D-xylose isomers? 10

Cyclisation of Monosaccharides Cyclisation of monosaccharides is spontaneous in aqueous solution. The sp 2 carbonyl carbon becomes sp 3 forming a new stereocentre. This carbon is called the anomeric carbon. C C 2 D-Glucose C 2 C 2 C 2 * * * New stereogenic centre The anomeric carbon This is an equilibrium reaction and the two stereoisomers (called anomers) will slowly interconvert. The six-membered ring form of a sugar is called a pyranose. This structural representation (a flat ring with in upper right position and substituents on vertical lines up or down) is called a AWRT projection 11

α and β anomers The α anomer of a D-monosaccharide has the group drawn down, trans to the C 2 group at C5. The β anomer of a D-monosaccharide has the group drawn up, cis to the C 2 group at C5. C 2 C C 2 C 2 α - anomer D-glucose β - anomer Names: α-d-glucopyranose and β-d-glucopyranose What about L-sugars, e.g. β-l-glucopyranose? 12

Mutarotation of Anomers C 2 C C 2 C 2 α - anomer open chain β - anomer Solution of pure α-d-glucopyranose in water has [α] D = +112.2 Solution of pure β-d-glucopyranose in water has [α] D = +18.7 After time, a glucose solution that reached equilibrium has [α] D = +52.7 implying 1/3 is in α form and 2/3 is in β form This spontaneous change in optical rotation as a pure anomer equilibrates to a mixture of anomers is MUTARTATIN Mutarotation is slow at p7, but is much faster when catalysed by acid 13

Cyclisation of Fructose C 2 C 2 2 C 2 C 2 C C 2 C 2 C 2 D-Fructose [ * memorise ] Forms a 5-membered cyclic hemiacetal Shape of furan, so is called a furanose remember tetrahydrofuran Called β-d-fructofuranose and α-d-fructofuranose 14

Stable conformation of Pyranose sugars Both Fischer and aworth projections are poor representations of the real shape of monosaccharides. Six membered pyranose rings will adopt a chair conformation with the substituents axial or equatorial The chair conformation with the most equatorial substituents will be most stable. C 2 2 C 2 C 1 1 3 3 3 α-d-mannopyranose 1 15

B. Aldehydes and Ketones Preparation of aldehydes and ketones: xidation of alcohols Aldehydes from 1 o alcohols PCC C 2 Cl 2 Ketones from 2 o alcohols [] 16

Reactions of aldehydes and ketones 1. Nucleophilic addition to Aldehydes and Ketones The δ+ Carbon will be attacked by nucleophiles. The xygen lone pair e- can be protonated by strong acid δ δ + Nu Negatively charged nucleophiles such as ˉ from NaB 4 These reactions are followed by addition of 3 + Neutral nucleophiles such as R These reactions work faster with an acid catalyst δ ++ Nu 17

Addition of Alcohol Acetal formation R' ketone R" 2 R + acid catalyst R R R' acetal R" 2 R' aldehyde 2 R + acid catalyst R' R acetal R 2 Le Chatelier s principle applies to the equilibrium Removing water from the system forms more acetal. Use c. 2 S 4 Adding excess water forms more ketone / aldehyde. Use 3 + Acetals are stable in neutral and basic medium but are hydrolysed by aqueous acid 18

Mechanism for acetal formation 2 R + R R 2 acid catalyst acetal Mechanism + R R R many more steps hemiacetal acetal 19

More about hemiacetals R R c. + R c. + 3 + 3 + R R 2 hemiacetal acetal emiacetals are intermediates in the formation of acetals. emiacetals are the product when a hydroxyl group and a carbonyl group are part of the same molecule and no other alcohol is present, e.g. sugars. = + hydroxy-carbonyl compound acid catalyst hemiacetal If another alcohol is present then the hemiacetal will be converted to the acetal. 20

Examples a ) b) 2 C 3 + 2 + acetal acetal c ) + + hemiacetal acetal d) carbonyl compound + 2 alcohol acetal + 21

Identification of acetals and hemiacetals ne carbon atom bonded to two oxygen substituents with single bonds Specify the starting materials (Ketone / Aldehyde and alcohol) from which the above compounds were made. 22

Exercise a ) b) conc + ethanol C + c ) d) + 3 c. + e ) 3 + f) c. + 23

Acetal formation in sugars = Glycoside formation The acetal of a sugar is called a glycoside The bond to the external alcohol is called a glycoside bond The alcohol can be as simple as methanol or it can be the hydroxyl group of a monosaccharide C 3 Methyl α-d-glucopyranoside Lactose β-(1, 4') glycoside bond 24

Exercises Find the glycoside bond(s) in maltose, cellulose and the most common form of starch amylopectin. What kind of glycoside bond will it be (α or β) (1,4 or 1,6 )? Maltose Which sugars make up these glycosides? Cellulose Amylopectin 25

Exercise Give the products, substrates or reagents for the following reactions: C 2 C 2 C 3 + C 2 C 3 C 2 C 2 3 + 26

2. xidation of aldehydes Easily oxidised by many oxidising agents because the can be removed during oxidation [] [] = Cr 3 / + or Tollens reagent R R Tollens' Test AgN 3 N 4 Ag Ketones are not oxidised because of strong C-C bonds 27

xidation of carbohydrates emi-acetal Aldehyde Carboxylic acid [] Aldoses are called reducing sugars because, in the process of being oxidised, they reduce the oxidising agent Tollens reagent: AgN 3, N 4 (Ag + Ag 0 silver mirror) 28

Predicting reducing sugars (mono- and disaccharides) C 2 D-glucose Tollens' test C C 2 D-gluconic acid Ag 0 All aldoses No ketoses No glycosides Except certain disaccharides Reducing sugars show mutarotation 29

Identify the reducing sugars: Maltose Sucrose C 2 C 2 C 2 C 3 C 2 Lactose 30

Shape C. Carboxylic Acids Physical properties of carboxylic acids ybridisation Bond angles Geometry around C Boiling points Exceptionally high Dimer due to hydrogen bonding Water solubility C1 to C4 are soluble, C5 is partly soluble, >C5 insoluble Alkali metal carboxylate salts are more soluble in water MM: 62 g.mol -1 bp: -10 ºC Na F R C Na 2 C MM: 60 g.mol -1 bp: 118 ºC 31 R

Acidity of carboxylic acids Remember A + 2 A - + 3 + [ 3 + ][A - ] K a = [A] pk a = - log K a Given pk a values, and doing the calculations means Cl C 3 C 2 pk a = -7 4.75 15.75 K a = 10 7 10-4.75 10-15.75 % dissociated = 99.97% 0.45% 0.000001% Carboxylic acids are weak acids compared to Cl but much stronger acids than water and alcohols 32

Reactions of carboxylic acids Reaction with a base to form a salt Na Na + 2 Reaction with an alcohol to form an ester Et conc + 2 rancid butter pineapple 33

D. Esters Fischer Esterification formation of esters carboxylic acid alcohol + ester water excess use as solvent remove to shift equilibrium to give product formation + + + + C 2 + Et 34

ydrolysis of esters The reaction adds water to the ester to break it into the carboxylic acid and alcohol from which it was made Acid catalysed hydrolysis is the reverse of Fischer water ester + alcohol carboxylic acid 3 + r Base induced hydrolysis Saponification See manufacture of soap 35

Mechanism of saponification ii) 3 + Write the products of the following saponification reaction: i. Na, 2 ii. 3 + 36

emiacetals, acetals or esters when do you get what? c 2 S 4 Et R c 2 S 4 Et c 2 S 4 Et Why the difference? C 2 c 2 S 4 Et 37

E. Amides R' Amides are completely non-basic (c.f. amines) because the lone pair is delocalised towards the carbonyl group and is not available for bonding to + N N N N R δ N R δ N Resonance forms = Normal line structures that do not accurately represent the amide structure. These line structures differ only in the position of their π- electrons. We say these line structures are imaginary. Resonance hybrid = The true structure. Average of all resonance forms. 38

Peptides The amide bond is very stable. It forms the backbone of proteins. The amide bond between two amino acids is called a peptide bond. Amino acids linked in this way are called peptides or polypeptides. When the polypeptide is big enough, it is called a protein. Restricted rotation of the amide bond is important for protein structure and activity. 39

ydrolysis of Amides N 2 N Requires prolonged heating with aqueous acid or base. (6M Cl at 100 ºC for 12 h) The chemical form of the products (carboxylic acid and amine) depends on the p of the solution. N 2 3 + N 4 N 2 N 3 40

Remember inorganic chemistry N 3 (aq) + Cl(aq) N 4 + (aq) + Cl - (aq) N 4 + (aq) + - (aq) N 3 (aq) + 2 C 3 C(aq) + - (aq) C 3 C - (aq) + 2 C 3 C - (aq) + Cl(aq) C 3 C(aq) + Cl - (aq) It is impossible to have N 3 or RC in an acidic solution It is impossible to have N 4 + or RC in a basic solution 41

Exercise Draw line structures of the products obtained after both acid and base hydrolysis of the following amides. N N ow about hydrolysis of the corresponding esters? 42

Summary of CMY127 reactions Alkynes Alkylhalides Alkenes Alkanes Alcohols Esters emiacetals Acetals Aldehydes Ketones Carboxylic acids Amides 43

Reaction Scheme - verview CMY127 X X X halohydrin alkane 1,2-dihalide Cl 2 Br 2 X 2, 2 2 Pd/C or Pt 2 2 Pd/C or Pt 2 X - X 2 Lindlar catalyst alkylhalide + / 2 alkene conc. 2 S 4 alkyne R SCl 2 or PBr 3 SCl 2 orpbr 3 X Na (or K) ester 2 + + or - R, + Jones 1 o alcohol 2 o alcohol 3 o alcohol NaB 4 PCC NaB 4 Jones or PCC Jones no reactio n alkoxide carboxylic acid Jones ortollens aldehyde ketone +, R +, 2 R acetal R +, 2 +, R R acetal R 44

The Full IUPAC nomenclature system Stereoisomerism Substituents Parent Unsaturation Functional group Stereoisomerism: Indicates whether double bonds are cis/trans or E/Z, and indicates stereocentres (R, S). Substituents: Are groups coming off the main chain, including alkyl chains and other functional groups. alides & ethers are always substituents Parent: Is the number of carbons in the main chain. Unsaturation: Indentifies if there are any double or triple bonds. Functional group: The most important functional group in the molecule. carbonyls > alcohols > thiols > amines > alkenes > alkynes > alkanes 45

Functional Groups in IUPAC names Name Formula Suffix when When named as a principal FG a Substituent Carboxylic acid RC 2, -oic acid Ester RC 2 R -oate Aldehyde RC -al Ketone RCR -one Alcohol R -ol hydroxy Thiol RS -thiol sulfanyl Amine RN 2,RNR,RNR 2 -amine amino (N 2 ) Alkene Alkyne Alkane -ene -yne -ane Ether RR alkoxy alide RX halo 46

Functional Groups and the Parent Identify all the functional groups and choose the highest priority group to give the suffix of the IUPAC name. Use the unsaturation block to indicate alkenes, alkynes or alkanes. The parent chain or ring must include as many functional groups as possible. The longest carbon chain or ring with all the functional groups gives the parent name. For equal lengths choose to have as many side chains as possible. Avoid branched alkyl substituents near the ends of the parent chain. For rings, add cyclo to the start of the parent. N 2 47

Naming substituents All extra functional groups as well as ethers and halogens get named as substituents. Alkyl branches from the parent get named as substituents indicating the number of carbons and the shape of the branch. Use di, tri, and tetra to indicate if there are 2, 3 or 4 of the same type of substituent. List the substituents in alphabetical order according to the name of the substituent. isopentyl isobutyl isopropyl t-butyl s-butyl phenyl benzyl 48

Numbering After finding the parent and naming the substituents, choose the direction of numbering. If there is a functional group, numbering is easy: number the chain from the end closest to the functional group R number the ring with 1 at the C with the functional group, or no 1 and 2 for the C s of an alkene then proceed around the ring to give the next functional group the smallest number. If there is no functional group revert to rules for branched alkanes: 49

Exercises Draw structures for the following compounds: 3-Chloro-2-isopropyl-1-butanethiol trans-2-sec-butyl-6-methyl-1,4-heptadien-3-ol 3-Methyl-2-cyclopentenol (E)-6-Bromo-5-heptene-3,4-diamine 50

Exercises Name the following compounds: S Br Br N 2 N 2 51