BIO-ORGANIC (Organic Chemistry for Biology Students) (SQBS 1603) Organic Compounds Containing Dr Nik Ahmad Nizam Bin Nik Malek, BSc (Ind. Chem.)(UTM), MSc (Chem)(UTM), PhD (Chem)(UTM), A.M.I.C Senior Lecturer, Department of Biotechnology and Medical Engineering Faculty of Biosciences and Medical Engineering Physical properties of the

Alkanes are insoluble in The alkanes have few direct water roles in biological systems

Biological systems are aqueous (water based)

Adding functional groups

2 The chemical components that What is ? are added to the simple skeleton of an organic compound. Molecules possessing the same functional group belong to the same family of To generate chemical diversity organic compounds. and functionality.

Hydrocarbon

Groups containing oxygen

Groups containing nitrogen

Groups containing phosphorus and sulfur

3 phosphate

Alcohol functional groups

Carboxylic acids Functional groups Biological importance of functional group Functional group Biological importance Lipids, carbohydrates Ethers Archael plasma membranes Ketone Metabolic intermediates Aldehyde Reducing sugars such as glucose Carboxylic acids Lipids, proteins Bacterial and eukaryotic plasma membranes Amines Proteins, nucleic acids DNA and RNA Amides Proteins, nucleic acids DNA and RNA Protein structure, Energy metabolism

Phosphate ATP, DNA 5 Functional groups

Groups containing oxygen Chemical Structural Group Formula Prefix Suffix Example class Formula

Methanol Hydroxyl ROH hydroxy- -ol Alcohol

Methyl ethyl ketone Ketone Carbonyl RCOR' keto-, oxo- -one (Butanone)

Acetaldehyde Aldehyde Aldehyde RCHO aldo- -al (Ethanal)

6 Functional groups Groups containing oxygen Chemical Structural Group Formula Prefix Suffix Example class Formula

Carboxylate Acetic acid

Carboxyl RCOOH Carboxy- -oic acid ()

Ethyl butyrate Ester RCOOR' (Ethyl butanoate) Esters alkanoate

Ethers ROR Di- -ether Diethyl ether

7 Functional groups Groups containing nitrogen

Chemical Structural Group Formula Prefix Suffix Example class Formula

Dimethylamine

RNH2

Amino R2NH amino- - Amines R3N

Acetamide

RCONH 2 RCONHR’ Carboxamide- -amide Amide RCONR 2

Functional groups Groups containing sulphur and phosporus

Chemical Structural Group Formula Prefix Suffix Example class Formula

Ethanathiol (Ethyl Mercapto- mercaptan) Thiol Sulfhydryl RSH -thiol Sulfanyl-

Glyceraldehyde 3-phosphate

ROP(=O)(OH) phoshate 2 phospho- Phosphate

9 Alcohol

• Alcohol – Hydroxyl group : -OH functional group – Generic formula: R-OH – General structure

R O H Alcohol • Classification

Hydroxyl O H C group

H R' R'

R C O H R C O H R C O H

H H R''

Primary (1) Secndary (2) Tertiary (3) 11 Naming

CH3 OH OH H2 H2 H3C C C C C CH3 H H

C : 6  hexane  hexanol

Methyl at C5

5-methyl-3-hexanol 6 5 4 3 2 1

12 Naming Alcohols • Give the IUPAC name of the following alcohol

2 Methyl at C3 H3C OH

3 1

4 6

5

C : 6  cyclohexane  cyclohexanol 3-methyl-cyclohexanol 13 Naming Alcohols

OH OH HO Ethanol -diol

IUPAC name: 1,2-ethanediol or -1,2-diol Common name: glycol

14 Reactions of alcohol

• Dehydration

• Oxidation

15 Dehydration

• Loss of water (H2O) • Elimination reaction – Elements of the starting material are lost and a new multiple bond is formed

H2SO4 C C C C H2O

H OH

H2O is lost Dehydration

• Examples

H H H H H2SO4 H C C H C C H2O H OH H H Ethanol Ethene OH

H2SO4 H2O H Cyclohexanol Cyclohexene

17 Dehydration • Zaitsev rule – The major product in elimination is the alkene that has more alkyl groups bonded to it.

H H H CH2CH3 H2SO4 H C C CH2CH3 C C H OH H H Butan-2-ol But-1-ene

H H H3C CH3 H2SO4 H3C C C CH3 C C Major OH H H H product Butan-2-ol But-2-ene 18 Oxidation

• Primary (1) alcohols – Oxidized to (RCHO) – And further oxidized to carboxylic acids (RCOOH)

O OH O [O] [O] C R C H C R H R OH H alcohol aldehyde Carboxylic acid

19 Oxidation • Secondary (2) alcohols

– Oxidized to (R2CO)

OH O [O] R C H C R R' R' alcohol ketones

20 Oxidation • Tertiary(3) alcohols – They are not oxidized

OH

R C R''

R'

21 Physical properties of alcohols

H H H H H H H H H H H C C H H C C OH C C C C C C H H H H H H H H H H

hydroxyl group  oxygen + hydrogen  highly electronegative atom  polar molecules

22 Physical properties of alcohols hydroxyl group  oxygen + hydrogen dipolar highly polar interaction electronegative molecules atom dispersion forces hydrogen bonding soluble in water in Strong non-covalent forces small quantity Exhibit higher melting and boiling points than alkanes 23 Physical properties of alcohols

high electron density Ethanol Low electron density

H2 - + - + 3HC C O H

Electron pulls towards highly electronegative oxygen atom The distribution of electrons within the molecules is unequal

The molecule is polar

24 Physical properties of alcohols hydrogen bonding O H H H 2 Ethanol is C H O attracted to the H C O water molecules 3 H H through hydrogen bonds O H H

25 Ether

– Alkoxy group : combination of an alkyl group and oxygen atom (alkyl + oxygen = alkoxy) – Generic formula: R-O-R’ – Similar to alcohol (hydroxyl group), except that the H atom is replaced with an alkyl group O O R H R R' Hydroxyl group Alkoxyl group

26 Ether

R O R

R groups are the H C O CH CH same 3 2 3

R groups are H3CH2C O CH2CH3 different

27 Naming Ether

Simple ethers: Usually assigned common names

O O

Methyl- Ethyl- Ethyl- Ethyl-

Ethyl methyl ether diethyl ether (methoxy-ethane) (ethoxy-ethane)

28 Naming Ether

More complex ethers: IUPAC name

H3C O H3CH2C O

Methoxy- Ethoxy-

29 Naming Ether

8 6 4 2 5 9 7 3 1

9 C  nonane O H3CH2C O Ethoxy- at position 3 3-ethoxy-nonane

30 Physical properties of ethers

Presence of oxygen  polar molecules

O

H3C CH3

Two polar bonds

31 Aldehydes and Ketones

O Carbonyl Carbonyl carbon group C

O O Aldehyde Ketone C C R H R R

32 Aldehydes and Ketones

O O Aldehyde Ketone C C R H R R

O O O O

C C C C H3C H Acetaldehyde H O

C H3C CH3 Propan-2-one 33 Naming aldehydes IUPAC name O

4 C  butane  butanal H CH O 3 Methyl  at 2 and 3  dimethyl 4 CH 2 C H C CH H 3 3 1

CH3

2,3-dimethylbutanal 34 Naming aldehydes • Simple aldehydes have common names that are widely used • Examples:

O O O C H C C H H H3C H Formaldehyde Acetaldehyde Benzaldehyde

35 Naming Ketones IUPAC name O

C 5 C  pentane  pentanone O 1 H C C 3 3 H2 C 2 CH 4 CH3 H3C 5

3-methyl-2-pentanone Carbonyl  position 2 Methyl  position 3

36 Naming Ketones • Common names for ketones: – Naming both alkyl group on the carbonyl carbon. – Arranging them alphabetically. – Finally, adding the word ketone. O ethyl methyl C H3C CH2CH3

IUPAC name: 2-butanone common name:

37 Ethyl methyl ketone Physical properties of aldehydes and ketones

Presence of oxygen  polar molecules Ether Aldehyde ketone - - O Electrons O O pulled H C CH towards 3 3 C highly C R H electrone gative R R Two polar bonds oxygen atom …….generating an uneven distribution of electron: polar molecule 38 Reactions of aldehydes and ketones

1. Oxidation of aldehydes O O [O] C C R H R OH Aldehyde Carboxylic acid 2. Reduction of aldehydes and ketones (addition reaction)

C O X Y C O

X Y 39 Oxidation of aldehydes • Examples O O K2CrO7 H CH CH C C 3 2 2 H3CH2CH2C C H OH Butyraldehyde Butyric acid

• How about ketones? O K2CrO7 H3CH2C C No Reaction

CH3 Butan-2-one 40 Reduction of aldehydes and ketones (addition reaction)

• Reduction – Decrease in the number of C-O – Increase in the number of C-H bonds • The conversion of a (C=O) to an alcohol is a reduction. – The starting material has more C-O bonds than the product

C O X Y C O

41 X Y Reduction of aldehydes and ketones (addition reaction) • Aldehydes – Reduce to primary (1) alcohol

O H [H] C R C O R H H H Aldehyde primary alcohol

O H [H] (CH CH OH) C H3C C O 3 2 H C H 3 H H Acetaldehyde Ethanol 42 Reduction of aldehydes and ketones (addition reaction) • Ketones – Reduce to secondary (2) alcohol O H [H] C R C O R R' R' H ketone Secondary

O H [H] ((CH ) CHOH) C H3C C O 3 2 H3C CH3 CH3 H Propan-2-one Propan-2-ol 43 formation • Aldehydes and ketones undergo addition reaction with alcohols to form hemiacetals and .

O H O R'-OH R''-OH OR'' R C OR' C R C OR' R H (or R) H2SO4 H2SO4 H (or R) H (or R) Aldehyde or ketone hemiacetal acetal 1 C is bonded to: 1 C is bonded to: -One OH group -two OR group -One OR group

44 Acetal formation • Example CH CH OH CH3CH2OH 3 2 O H O CH2CH3 O Ethanol Ethanol H CH C C OCH CH H3CH2C C OCH2CH3 C 3 2 2 3 H CH C H H SO 3 2 H2SO4 H 2 4 H Propionaldehyde 1-Ethoxy-propan-1-ol 1,1-Diethoxy-propane hemiacetal acetal

CH CH OH CH3CH2OH 3 2 O H O CH2CH3 O Ethanol Ethanol H3C C OCH2CH3 C H3C C OCH2CH3 H C CH 3 3 H SO H2SO4 CH 2 4 CH3 3 Propan-2-one 2-Ethoxy-propan-2-ol 2,2-Diethoxy-propane hemiacetal acetal

45 Cyclic hemiacetals

1 C is bonded to: -One OH group -One OR group

OH OH OH

R C OR O H (or R) O

1 C is bonded to: -One OH group -An OR group that is part of a ring

46 Cyclic hemiacetals • Formation of cyclic hemiacetals – Intramolecular reaction of a compound that contain both a hydroxyl group (-OH) and aldehyde or ketone.

O OH

O 1 H 1 2 2 O 5 4 3 2 C OH 1 3 3 5 HOH2CH2CH2CH2C H 5 4 4 5-Hydroxy-pentanal

47 Carboxylic Acids • Carboxyl group: Combining the hydroxyl and carbonyl.

• Generic formula: RCOOH or RCO2H O carbonyl

C

R hydroxyl OH

48 Naming Carboxylic acids • IUPAC system  suffix –oic acid O 6 C  hexane  OH hexanoic acid

CH3 O 2 methyl at

6 4 H2 2 position 4 and 5 CH C C  4,5-dimethyl- H3 5 CH 3 C 1 OH C H2

CH3

4,5-dimethylhexanoic acid 49 Naming Carboxylic acids • Many simple carboxylic acids are often referred to by their common names.

O O O C C C OH H OH H3C OH Formic acid Acetic acid

IUPAC name: IUPAC name: Benzoic acid methanoic acid ethanoic acid IUPAC name: benzenecarboxylic acid

50 Physical properties of carboxylic acids

O 2 oxygen atoms C R H O

2 very electronegative atoms attach with each other

51 Physical properties of carboxylic acids

O

• Polarity? C R H • Dipolar interaction? O • Hydrogen bonding between molecules of same compound? • Hydrogen bonding with water? • Solubility in water? • Boiling point?

52 Physical properties of carboxylic acids

Presence of oxygen + hydrogen (carbonyl and hydroxyl group)  polar molecules

O Hydrogen bonding between molecules of C same compound R H O

53 Physical properties of carboxylic acids

• Hydrogen bonding with water? • Solubility in water?

H H H H O O O C R H O

H H O

54 The acidity of carboxylic acids

O O

H2O H3O C C R O H R O

carboxylic acid carboxylate anion

O O

H2O H3O C C H C O H 3 H3C O Acetic acid Acetic acid anion acetate

55 Reaction with bases

O O NaOH H-OH C C H C O H + 3 H3C O Na Acetic acid Sodium acetate

Carboxylate anions

56 Carboxylate anions

O O NaOH or C + C O Na or O H KOH K+ Hexanoic acid

Carboxylate anions: sodium or potasium hexanoate

Name of the Parent metal cation -ate (suffix) (e.g. hexane) (e.g: sodium) + +

57 Conversion of carboxylic acids to esters and amides

H SO O Formation O 2 4 H-OR' of ester H-OH C C R O H alcohol R O R Carboxylic acid ester

O Formation O  of amide H-NH2 H-OH C C R O H ammonia R NH2 Carboxylic acid amide

58 Esters • A modified carboxyl group • Generic formula: RCOOR’ OH and H O combined to form Carboxylic H O acid 2 C R H O H O R' alcohol

O O

C O R' R O C R O R' 59 Naming esters

• IUPAC system  suffix –ate • Two parts 1. Name the (RCO-) by changing the –ic ending of the parent carboxylic acid to the suffix –ate. 2. Name the R’ group bonded to the oxygen atom as an alkyl group.

O

Acyl group C R O R' Alkyl group

60 Naming esters

O

O 4 C  butanoic acid  butanoate

O

H2 C C CH3 R’ = methyl H3C C O H2

Methyl butanoate

61 Physical properties of esters

O O

OH O

Carboxylic ester acid

62 Physical properties of esters

• Polarity? • Dipolar interaction? • Hydrogen bonding between molecules of same compound? • Hydrogen bonding with water? O • Solubility in water? • Boiling point? O

63 Ester formation from carboxylic acids • Substitution – All acyl (RCO) compounds.

O O H-Y H-Z C C R Z R Y

Y=OH, OR', NR2' Z = OH, OR', NR'2 Y replaces Z

64 Ester formation • Fischer esterification – Treatment of carboxylic acid (RCOOH) with an alcohol (R’OH) in the presence of an acid catalyst forms an ester (RCOOR’). – example O O

H-OCH2CH3 H-OH C C H C OCH CH H3C OH 3 2 3 Acetic acid ethyl acetate

65 REFERENCES

• Crowe, J., Bradshaw, T. and Monk, P. (2006), Chemistry for the Biosciences: The Essential Concepts, Oxford University Press, Oxford. • Horton, H.R., Moran, L.A., Scrimgeour, K.G., Perry, M.D. and Rawn J.D. (2006). Principles of Biochemistry, 4th Edition. Pearson International Edition. • Smith, J.G. (2010). General, Organic and Biological Chemistry. McGraw-Hill Higher Education. • Denniston, K.J., Toping, J.J. and Caret, R.L. (2008). General, Organic and Biochemistry, 6th edition. McGraw-Hill Higher Education.

MY PROFILE

Dr Nik Ahmad Nizam Bin Nik Malek, BSc (Ind. Chem.)(UTM), MSc (Chem)(UTM), PhD (Chem)(UTM), A.M.I.C Senior Lecturer, Department of Biotechnology and Medical Engineering, Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia. Email: [email protected], [email protected] Website: http://www.staff.blog.utm.my/niknizam/