Organic Chemistry A-Levels H2 CHEMISTRY FORMULAE Compound 2-methylhex-3-ene 3-methylpentanoic acid 3-nitrophenol CH2 C3H6O C6H5NO3 C7H14 C6H12O2 C6H5NO3 CH3CH(CH3)CHCHCH2CH3 CH3CH2CH(CH3)CH2COOH or or Type of formulae Empirical formula (Ratio of the number of atoms of each element present in one molecule) Molecular Formula (Actual number of atoms of each element present in one molecule) Structural Formula (Shows how the constituent atoms of a molecule are joined together) H3 C Displayed Formula/ Full Structural Formula (Shows all bonds and atoms in a molecule) H CH3 H H CH C C CH2 CH3 H3C CH2 CH CH2 COOH H H H H H H C C C C C C H H HH C H H OH O2N CH3 H H H H H H C C C C H H H C H H H O O C O H H O N O In writing displayed formula for ring structures, is the convention for representing benzene, C6H6 is acceptable for cyclohexane, C6H12 Page 2 ISOMERISM Structural Isomerism (exhibited by substances with the same molecular formula but different structural formula) Stereoisomerism (exhibited by substances with the same attachment of atoms to each other but different spatial arrangement) Functional Group Isomerism (same molecular formula, different functional groups) H3C CH2 OH alcohol H3C O Geometric Isomerism (cis-trans) (caused by restriction of rotation of double bond or ring) CH3 • ether Positional Isomerism (same molecular formula, different positions of the functional group) Found in alkenes when the two groups attached to each of the two carbons in the double bond are different. Br 1-brom opr opane H 3C CH Br C Br H 3C C H 2 C H 2 B r Chain Isomerism (same molecular formula, skeletal chain) H • H B u t a n -1 -o l C Br C Br trans-isomer Double bonds in a ring do not have geometric isomers as there can only be the cis configuration. CH3 H 3 C C H 2 C H 2 C H 2 O H H 3C C H CH3 H C cis-isomer 2-bromopr opane Br C H CH 3 Optical Isomerism (present in molecules with no plane of symmetry; molecules can exist as two non-superimposable mirror images) Compounds with chiral carbons can exhibit optical isomerism • • • • CH2 OH 2 -me th ylpropa n-1- ol Total number of stereoisomers n 2 where n = no. of chiral carbons + no. of C=C double bonds which can exhibit geometric isomerism • • OH H CH3 HO H C Br A compound that exhibits optical isomerism has two enantiomers. These enantiomers are non-superimposable mirror images. Each mirror image is optically active and is able to rotate plane-polarised light. A racemic mixture which consists of the two enantiomers in equal proportions, is optically inactive (does not rotate plane-polarised light). Enantiomers have the same physical properties except for the direction in which they rotate plane polairsed light. They have the same chemical properties except when reacting with other chiral compounds. Nucleophilic addition reactions of carbonyls and Electrophilic addition reactions of alkenes can form products that are racemic mixtures. Page 3 Br2(l) in CCl4 SYNTHETIC ROUTES INVOLVING ALKANES & ALKENES H C H uv or heat H H C Cl H C C H industrial method: H2O(g), 300 ºC, 60 atm, conc. H3PO4 ethanolic KOH (or NaOH) H H heat Br H C H C laboratory method: conc. H2SO4 followed by H2O(l), warm C H C H2(g) / Ni catalyst 170 ºC H 150 ºC OH Reduction or addition conc. KMnO4 / H2SO4 heat H H C conc. KMnO4 / H2SO4 H3C H3C C conc. KMnO4 / H2SO4 Oxidation (oxidative cleavage) H industrial method: H2O(g), 300 ºC, 60 atm, conc. H3PO4 HO laboratory method: conc. H2SO4 followed by H2O(l), warm O CH3 CH3 H H3C H3C H3C C heat cold, dil. KMnO4 / NaOH(aq) CO2(g) + H2O(l) C heat C Br Br H H C C Br OH H H C C H OH H H C C H H H H C C H H C C H OH H H OH OH CH3 CH3 CH3 C HBr(g) H3C H CH3 C O H Electrophilic addition ethene excess conc. H2SO4 H H oxidation H H3C H H C Elimination H H H Electrophilic addition H H C Br2(aq) Free radical substitution H methane H H limited Cl2(g) H H Electrophilic addition H CH3 2-methylbut-2-ene Electrophilic addition H C C H Br CH3 Ethanedioic acid (HOOC-COOH) can be further oxidised to CO2 and H2O. Page 4 SYNTHETIC ROUTES INVOLVING BENZENE AND METHYLBENZENE CH3 CH3 NO2 conc. HNO3 / conc. H2SO4 30 ºC Electrophilic substitution Br2(l) / FeBr3 Br NO2 Electrophilic substitution CH3 CH3 CH3 CH3Cl / AlCl3 Br2(l) / FeBr3 benzene Br or Br2(l) / Fe(s) Electrophilic substitution methylbenzene Electrophilic substitution conc. HNO3 / conc. H2SO4 Br NO2 60 ºC nitrobenzene Electrophilic substitution CH2Cl May have multiple substitution at higher temperature Reduction 1. Sn / conc. HCl, heat Free radical substitution limited Cl2(g) uv or heat 2. NaOH(aq) NH2 Oxidation COOH KMnO4 / H2SO4(aq) with heat benzoic acid phenylamine or 1) KMnO4 / NaOH , heat 2) Acidify with H2SO4 (aq) Page 5 SYNTHETIC ROUTES INVOLVING HALOGENOALKANES CH3 NaOH(aq) CH3 H C H H heat Br2(l) C Nucleophilic substitution OH H uv or heat Free radical substitution H H H ethanolic NaOH heat CH3 H H C HBr(g) H C H H C C H Br H CH3 bromoethane Nucleophilic substitution concentrated ethanolic NH3 H C heat in sealed tube NH2 H Substitution CH3 Elimination of 2-chlorobutane can produce 3 alkenes – but-1-ene, cis but-2-ene and trans but-2-ene elimination H Electrophilic addition C PBr3 H C H OH or NaBr with conc. H2SO4 (equivalent to HBr), heat *If PCl5 is used to obtain the chloroalkane, no heat is required* Nucleophilic substitution ethanolic KCN H heat Reduction CH3 C CN CH3 LiAlH4 in dry ether Or H2, Ni (high T,P) H H CH3 H C COO Na H + NH3 C CH2NH2 H Hydrolysis Hydrolysis NaOH(aq) H2SO4(aq) heat heat CH3 H C COOH H + NH4+ Page 6 SYNTHETIC ROUTES INVOLVING PRIMARY ALCOHOLS Other chlorinating reagents: SOCl2, PCl3, HCl with ZnCl2 CH3 H C Cl CH3 H PBr3 Electrophilic addition H H C C industrial method: H2O(g), 300 ºC, 60 atm, conc. H3PO4 PCl 5 (s) r.t. C Br H CH3 PI3 H heat substitution laboratory method: conc. H2SO4 followed by H2O(l), warm H H Other brominating reagent: NaBr with conc. H2SO4 (equivalent to HBr), heat C I H H O K2Cr2O7 / H2SO4 CH3 H C H H reduction LiAlH4 in dry ether O H3C or NaBH4 C H CH3 heat X = Cl, Br or I C oxidation NaOH(aq) X H3C heat with immediate distillation Nucleophilic substitution C OH O K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 H3C heat H ethanol OH oxidation or H2 / Ni, high T, P elimination H H excess conc. H2SO4 reduction OH Ethanol is the only primary alcohol that undergoes iodoform reaction O H O Na CH3COOH + conc. H2SO4 + heat or CH3COCl or CH3COBr CH3 + CHI3 C H C H condensation warm C I2(aq) / NaOH(aq) H3C LiAlH4 in dry ether H C 170 ºC O C redox H C H3C C O Na(s) oxidation O CH2CH3 O Na H Page 7 SYNTHETIC ROUTES INVOLVING SECONDARY ALCOHOLS CH3 PCl 5 H CH3 C C H H industrial method: H2O(g), 300 ºC, 60 atm, conc. H3PO4 H C Other chlorinating reagents: SOCl2, PCl3, HCl with ZnCl2 Cl CH3 laboratory method: conc. H2SO4 followed by H2O(l), warm CH3 PBr3 H C Other brominating reagent: NaBr with conc. H2SO4 (equivalent to HBr), heat Br CH3 CH3 C PI3 X NaOH(aq) I C CH3 CH3 heat CH3 H X = Cl, Br or I LiAlH4 in dry ether O or NaBH4 C OH O K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 C heat CH3 H 3C Orange K2Cr2O7 turned green Purple KMnO4 decolourised propan-2-ol CH3 or H2 / Ni, high T, P C CH3 Only methyl alcohols, –CH(OH)CH3, will undergo iodoform reaction I2(aq) / NaOH(aq) H 3C H heat H or CH3COCl or CH3COBr Na(s) H C H3C CH3 C O CH3 O Na H O CH3COOH + conc. H2SO4 + heat O Na Tertiary alcohols cannot be oxidised. C H + CHI3 C C 170 ºC O H3C CH3 excess conc. H2SO4 warm H CH3 C H Elimination of butan-2-ol can produce 3 alkenes – but-1-ene, cis but-2-ene and trans but-2-ene CH3 CH3 Page 8 SYNTHETIC ROUTES INVOLVING PHENOLS OH OH Br2(l) in CCl4 O Na Redox (Na) Acid-base (NaOH) Br Electrophilic substitution Na(s) or NaOH(aq) Br OH OH Phenol cannot react with carboxylic acid to form ester. Phenol is a poor nucleophile as the lone pair on oxygen is delocalized into the benzene ring. Electrophilic substitution acid chloride RCOCl or acid bromide RCOBr Br 3Br2(aq) Condensation + 3HBr room temperature Br phenol O C O Br R acid chloride RCOCl or acid bromide RCOBr Electrophilic substitution OH OH dil. HNO3(aq) Condensation NO2 OH conc. HNO3 Electrophilic substitution O2 N NO2 NO2 Phenols cannot be oxidised. NO2 Page 9 SYNTHETIC ROUTES INVOLVING ALDEHYDES O Oxidation K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 − CH3COO + Ag (s) H3C C heat Note: Benzaldehyde gives negative results with Fehling’s solution but gives positive results with Tollen’s reagent on warming. OH Silver mirror or grey ppt CH3COO− + Cu2O (s) Red ppt H C LiAlH4 in dry ether Tollen’s reagent (also known as ammonical silver nitrate) Fehling’s solution or NaBH4 C OH H Oxidation heat with immediate distillation O Oxidation I2(aq) / NaOH(aq) O K2Cr2O7 / H2SO4 OH H or H2 / Ni Oxidation CH3 CH3 Reduction H3C C warm or H Condensation 2,4-dinitrophenylhydrazine Orange ppt H3 C C H CH2NH2 LiAlH4 in dry ether C Nucleophilic Addition N H C N NO2 H NaOH(aq) heat CN H3C Hydrolysis or H2 / Ni, high T, P NO2 OH OH H3C Ethanal is the only aldehyde that undergoes iodoform reaction H3C KCN + H2SO4 Reduction Yellow ppt O Na HCN with trace KCN (or trace NaOH) OH CHI3 C ethanal H H + C COO Na Acid-base H H dil. NaOH(aq) dil. H2SO4(aq) OH dil. H2SO4(aq) heat Hydrolysis H3C C COOH H Page 10 SYNTHETIC ROUTES INVOLVING KETONES H LiAlH4 in dry ether H3C or NaBH4 C OH CH3 or H2 / Ni O I2(aq) / NaOH(aq) Ketones cannot undergo oxidation. C + CHI3 C heat O Na O H H3C H3C Only methyl ketones, –COCH3, will undergo iodoform reaction OH K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 H3C C heat H3C CH3 CH3 NO2 2,4-dinitrophenylhydrazine propanone C N H3C HCN with trace KCN (or trace NaOH) N NO2 H or KCN + H2SO4 OH H3C C OH OH CH2NH2 LiAlH4 in dry ether H3C C NaOH(aq) heat CN H3C COO Na CH3 or H2 / Ni, high T, P CH3 C CH3 dil. NaOH(aq) OH dil. H2SO4(aq) heat dil. H2SO4(aq) H3C C COOH CH3 Page 11 SYNTHETIC ROUTES INVOLVING CARBOXYLIC ACIDS H3C C C H LiAlH4 in dry ether Reduction heat H H C C OH Oxidation OH O K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 PCl 5 heat H3C Cl O O K2Cr2O7 / H2SO4 or KMnO4 / H2SO4 C Oxidation heat H3C C or Na2CO3(aq) ethanoic acid H O Na(s) or NaOH(aq) OH H H H3C CN H + H2O (if reacts with NaOH) C O Na + CO2 (if reacts with Na2CO3) H2SO4(aq), heat or NaOH(aq), heat followed by addition of H2SO4(aq) Carboxylic acids cannot react with phenols to form esters. O CH3CH2OH heat with conc. H2SO4 H3C C Condensation O O CH2CH3 H2O(l) C Hydrolysis Cl Hydrolysis O H3C + H2 (if reacts with Na) Hydrolysis C H3C Other chlorinating reagents: SOCl2, PCl3 C H H3C Acids cannot be reduced by H2, Ni, nor NaBH4 H CH3 H CH3 Oxidation conc. KMnO4 / H2SO4 CH3 H2SO4(aq), heat C O CH2CH3 O NH3(aq) Acid-base H3C C O NH4 or NaOH(aq), heat followed by addition of H2SO4(aq) Page 12 H2O(l) SYNTHETIC ROUTES INVOLVING ACID CHLORIDES Hydrolysis O H3C C + HCl OH O NaOH(aq) H3C C + HCl O Na O CH3CH2OH Condensation H3C + HCl C O O O H3C PCl 5 C H3C C O Cl OH CH2CH3 O ethanoyl chloride H3C C + Cl – O Other chlorinating reagents: SOCl2, PCl3 O NH3 Condensation H3C C Primary Amide + HCl NH2 O CH3NH2 Condensation H3C Secondary Amide C N CH3 + HCl H Page 13 SYNTHETIC ROUTES INVOLVING AMINES, AMIDES AND PHENYLAMINES CH3 CH3Br Nucleophilic Substitution H Nucleophilic Substitution CH3 Concentrated ethanolic NH3 H C X heat in sealed tube Acid-base X = Cl, Br or I CH3 LiAlH4 in dry ether CN H C NH2 ethylamine Acid-base heat C CH3 O C NH3 Cl H CH3 Condensation Hydrolysis Hydrolysis heat O + NH3 H3C C O C N H H NH2 NO2 + NH4+ OH O Na H dil. H2SO4(aq) ethanamide C NH3 CH3COCl O H3C H LiAlH4 in dry ether NH2 NaOH(aq) C O CH3 Reduction C H HCl(aq) H H3C H CH3 H or H2, Ni high T, P O H CH3 Reduction N CH3 CH3CO2H H C Reduction C Electrophilic Substitution CH3 + HCl NH2 Br Br 3Br2(aq) 1. Sn / conc. HCl, heat 2. NaOH(aq) dil. H2SO4(aq) NaOH(aq) phenylamine Br Phenylamine and phenol give the same observation when reacted with aqueous bromine. They can be distinguished by their respective solubility in acids and bases. Page 14 MECHANISM: Free Radical Substitution CH4(g) + Cl2(g) Organic compounds involved: Reagents: Conditions: 1. CH3Cl(g) + HCl(g) uv or heat Alkanes or organic compounds with alkyl side chain. Cl2(g) or Br2(l) uv or heat Initiation Homolytic fission of the Cl-Cl bond Cl 2. Cl 2Cl The position and extent of substitution cannot be controlled. Propagation Cl + CH4 CH3 3. uv or heat CH3 + Cl2 CH3Cl + Cl CH3Cl + Termination CH3 Cl CH3 + Cl + CH3 Cl2 HCl + Cl For example, when CH3CH2CH2CH3 is mixed with chlorine gas, possible products include CH3CH2CH2CH2Cl, CH3CH2CHClCH3, and CH3CH2CH2CHCl2 etc. Hydrogen radical is not formed in the reaction. CH3CH3 Page 15 MECHANISM: Electrophilic Substitution C6H6 conc. HNO3 + conc. H2SO4 C6H5NO2 Other possible substitution reaction 60 ºC Organic compounds involved: Reagents: Conditions: Electrophilic substitution of bromine using bromine liquid with a Lewis catalyst (e.g. FeBr3 or Fe) Aromatic compounds conc. HNO3 + conc. H2SO4 60 ºC Br2 + FeBr3 ! Br+ FeBr4– FeBr3 can be generated in-situ: 1. Generation of electrophile 2H2SO4 2. 3Br2 + 2Fe NO2 HNO3 H3O ! 2FeBr3 2HSO4 Electron-rich benzene attacks electrophile to form an intermediate. H NO2 NO2 slow (arenium ion) 3. Stability of the aromatic ring regenerated with the removal of a proton by HSO4–. HSO4 H NO2 NO2 fast + H2SO4 (regenerated) Page 16 MECHANISM: Nucleophilic Substitution CH3CH2Br + NaOH(aq) heat under reflux Organic compounds involved: Reagents: Conditions: CH3CH2OH + NaBr Halogenoalkanes NaOH(aq) heat under reflux Nucleophilic Substitution Bimolecular SN2 H d+ H C HO H3C Br H d– HO H H H C CH3 Br HO C + Br CH3 transition state • • • • • One-step mechanism Rate = k [halogenoalkane] [OH–] Simultaneous bond breaking and bond forming resulting in a transition state where the entering nucleophile and the leaving halide ion are both partially bonded to the same carbon atom. Nucleophile approaches electron deficient carbon from the opposite side to the halogen atom. Product undergoes inversion of configuration (if the carbon bonded to the halogen atom is chiral) Other nucleophiles to react with halogenoalkanes may include cyanide ion (CN–) or ammonia (NH3). H3N: NC- : Page 17 Nucleophilic Substitution Unimolecular SN1 1. Heterolytic fission of the C–X bond to give a carbocation (an intermediate) and a halide anion. This is the rate-determining step. CH3 H3C d+ C d– slow Br R1 CH3 H3C R3 + C OH C R2 Br CH3 CH3 OH 2. The carbocation is very reactive and is readily attacked by the nucleophile (e.g. OH–). OH CH3 H3C C fast OH CH3 H3C C CH3 • • Two-steps mechanism Rate = k [halogenoalkane] CH3 C R1 OH R3 R2 C R3 R2 R1 If the halogenoalkane is optically active, a racemic product is obtained since attack by the hydroxyl group (OH–) can take place from both sides of the carbocation, yielding equal quantities of both the optical isomer. Thus the product is optically inactive. Page 18 MECHANISM: Electrophilic Addition C2H4 + Br2(l) C2H4Br2 Addition of hydrogen halides (Markovnikov’s Rule) Organic compounds involved: Reagents: Conditions: Alkenes. Br2(l) / CCl4 room temperature in the absence of light H H C H 1. H C Br CH3 Bromine molecule polarized by approaching alkene molecule which allows the p–electrons to attack the electrophile to form a bromonium ion intermediate, containing a three-membered ring with the positive charge on the bromine. H H H C H C d+ d– Br Br Br slow C H H C H H H H Br H C H H H CH3 H C C positive charge on the more substituted carbon C H CH3 positive charge on the less substituted carbon Less stable, not formed. (bromonium ion) 2. Reaction is completed by the attack of the anion on the bromonium ion, yielding a saturated product. Br C H fast C H H C H H H Br Br Br H Bromonium ion can be drawn as Br + C C H H C H H H H Br C C H CH3 H The addition of a proton to the double bond of an alkene results in a product with the hydrogen bonded to the carbon atom that already has more hydrogen atoms. H Page 19 MECHANISM: Nucleophilic Addition CH3CHO + trace KCN HCN Organic compounds involved: Reagents: Conditions: 1. CH3CH(OH)CN Carbonyl compounds HCN with trace KCN cold Nucleophile attacks electron-deficient carbonyl carbon to form a tetrahedral intermediate anion. H3C d+ d– C O H3C s lo w H C H O CN NC NC t e t r a h e d ra l i n t e r m e d i a t e H3C C 2. The intermediate will be protonated by attacking an undissociated HCN molecule, regenerating CN– anion. (KCN acts as a catalyst) O H CN H 3C H C NC H3C O H CN H fast C OH NC cyanohydrin + CN If a chiral carbon results from the addition reaction, the product mixture will be optically inactive as the nucleophile may attack the planar carbonyl carbon on equally from either sides (top and bottom) that results in a racemic mixture. Page 20 COMMON REAGENTS Reagents Conditions Functional Group(s) Expected Observation Alkenes Reddish-brown bromine decolourised Remarks Electrophilic addition reaction. - Dibromo-derivative formed. CH2=CH2 + Br2 ! CH2BrCH2Br Electrophilic substitution reaction Monobromo-derivative formed. OH OH OH Br + Br2(l) in CCl4 Phenols Phenylamines Br2(l) + Reddish-brown bromine decolourised Br 2-bromophenol 4-bromophenol NH2 NH2 NH2 Br + + Br2(l) Br 2-bromophenylamine 4-bromophenylamine Free radical substitution reaction. heat or uv light Alkanes Alkyl chains Extent and position of substitution cannot be controlled. Reddish-brown bromine decolourised Probability vs stability of radicals: tertiary > secondary > primary > methyl CH4 + Br2 ! CH3Br + HBr Electrophilic substitution reaction. Monobromo- or monochloro- derivative formed. Br2 (with FeBr3 or AlBr3) or Cl2 (with FeCl3 or AlCl3) - Benzene Substituted benzene Reddish brown bromine decolourised. FeBr3 + Br2 Br + HBr Page 21 Reagents Conditions Functional Group(s) Expected Observation Remarks Electrophilic addition reaction. - Alkenes Orange red solution decolourised. Bromoalcohol formed as the major product. CH2=CH2 + H2O + Br2 ! CH2(OH)CH2Br + HBr Confirmatory test for alkenes Electrophilic substitution reaction. Tribromo-derivative formed. OH OH Br + Br 3Br2(aq) + 3HBr(aq) + 3HBr(aq) Br2(aq) - Phenols Phenylamines Br Orange red solution decolourised. White precipitate formed 2,4,6-tribromophenol (white ppt) NH2 NH2 Br + Br 3Br2(aq) Br 2,4,6-tribromophenylamine (white ppt) Confirmatory test for phenol and phenylamine. Catalyst not required as –OH and –NH2 groups are strongly activating. Page 22 Reagents Conditions Functional Group(s) - Acid chlorides Expected Observation White precipitate (AgCl) AgNO3(aq) Remarks Hydrolysis of acid halides with precipitation reaction. No need to add NaOH(aq) first as the halides leave easily on contact with water. O - Acid bromides Cream precipitate (AgBr) O + C Ag+(aq) + H2O + AgX(s) + H+ C X OH (X = Cl or Br) H2O(l) - Reagents Conditions Acid chlorides Acid bromides Functional Group(s) Hydrolysis of acid halides. White fumes RCOX + H2O ! RCOOH + HX Expected Observation (X = Cl or Br) Remarks Electrophilic Addition reaction. Markovnikoff’s rule applies HBr(g) or HCl(g) - Alkenes - Stability of carboncation: tertiary > secondary > primary H CH3 C H HBr(g) generated from NaBr with conc.H2SO4 C + HBr H H H CH3 C C H Br H Substitution reaction. Alcohols - Halogen atom replaces –OH group. CH3CH2–OH + HBr ! CH3CH2–Br + H2O Substitution reaction. HCl(g) with ZnCl2 catalyst Alcohols - Halogen atom replaces –OH group. CH3CH2–OH + HCl ! CH3CH2–Cl + H2O Page 23 Reagents Conditions Functional Group(s) Expected Observation Remarks Condensation reaction. The hydrazone derivative is formed. O2N 2,4-dinitrophenylhydrazine (2,4-DNPH) Aldehydes Ketones - Orange precipitate formed. C R' O2N H R R N O + H R, R' = alkyl or H N NO2 H C R' N N NO2 + H2O H 2,4-dinitrophenylhydrazine Confirmatory test for carbonyl group (aldehydes or ketones). Redox reaction. Cu2+ reduced to Cu+ (Cu2O). Fehling’s solution heat Aldehydes (except Benzaldehyde) Reddish-brown precipitate formed RCHO + 2Cu2+ + 5OH– ! RCOO– + Cu2O + 3H2O Confirmatory test for aldehydes except benzaldehyde. Tollens’ reagent (Ammonical silver nitrate) heat Benzaldehydes CH3 I2(aq) with NaOH(aq) heat Redox reaction. Ag+ reduced to Ag(s) Aldehydes C O OH C CH3 R Silver mirror formed Yellow crystals of tri-iodomethane (CHI3) formed. RCHO + 2Ag(NH3)2+ + 3OH– ! RCOO– + 2Ag + 4NH3 + 2H2O Iodoform reaction is a method of shortening a chain by a single carbon atom. RCH(OH)CH3 + 4I2 + 6OH– ! RCOO– + CHI3 + 5I– + 5H2O RCOCH3 + 3I2 + 4OH– ! RCOO– + CHI3 + 3I– + 3H2O Nucleophilic addition reaction. HCN (with trace of NaOH; or with trace of KCN) cold Aldehydes Ketones - CH3COCH3 + HCN ! (CH3)2C(OH)CN Carbon chain extended by one. Two functional groups on one carbon. Page 24 Reagents Conditions Functional Group(s) Expected Observation Remarks Acid hydrolysis. Dilute acids (HCl, HNO3, H2SO4) Nitriles heat Amides CH3CN + H+ + 2H2O ! CH3COOH + NH4+ - CH3CONH2 + H+ + H2O ! CH3COOH + NH4+ Esters CH3COOCH3 + H2O ! CH3COOH + CH3OH Electrophilic addition reaction. Markovnikoff’s rule applies to the addition process. - Alkenes - Addition of concentrated sulphuric acid followed by warming with water CH2=CH2 + H2O ! CH3CH2OH Elimination reaction. –OH group and –H atom on adjacent carbon are removed. Excess conc. H2SO4 is used. Concentrated H2SO4 170 °C Alcohols - CH3 CH3 H C C H OH H excess conc. H2SO4 170 oC H3C CH3 C H C H H (major) CH2CH3 C C H + H2O H (minor) May have more than one alkene formed. The more substituted alkene is the major product. Condensation reaction. 60 °C Alcohol + Carboxylic acid - Concentrated sulphuric acid is used as a catalyst. (Dehydrating agent) CH3CH2COOH + CH3CH2OH ⇌ CH3CH2CO2CH2CH3 + H2O Page 25 Reagents Conditions Functional Group(s) Expected Observation Remarks Electrophilic substitution reaction. 60 °C C6H6 + HNO3 ! C6H5NO2 + H2O Benzenes CH3 CH3 Concentrated HNO3 (with conc. H2SO4) Yellow oil produced conc. H2SO4 + HNO3 30 °C (methylbenzene) CH3 NO2 + H2O 30 oC Substituted benzenes NO2 2-nitromethylbenzene 4-nitromethylbenzene Electrophilic substitution reaction. Tri-substitution occurs when concentrated nitric acid is used. OH OH O2N Concentrated HNO3 - Phenols + White precipitate NO2 3HNO3 + 3H2O NO2 phenol 2,4,6-trinitrophenol Note: Mono-substitution occurs when dilute nitric acid is used. Reagents Conditions Functional Group(s) Expected Observation Remarks Complex formation. 3 Neutral FeCl3(aq) - Phenol Violet colouration Fe3+(aq) + 6 OH Fe O + 6H+ 6 Confirmatory test for compounds with phenol functional group. Page 26 Reagents Conditions Functional Group(s) Expected Observation Decolourisation of purple solution with effervescence. H C H Remarks Oxidative cleavage of terminal alkene. CO2 and H2O produced Oxidative cleavage. R Carboxylic acid produced. C H CH3CH=CH2 + 5[O] ! CH3COOH + H2O + CO2 (R = alkyl) Decolourisation of purple solution. R C R' Oxidative cleavage. Ketone produced. (CH3)2C=CH2 + 4[O] ! (CH3)2CO + H2O + CO2 (R = alkyl) Side chain oxidation. Benzoic acid produced. CH3 C6H5CH3 + 3[O] ! C6H5COOH + H2O H H Concentrated KMnO4 with H2SO4(aq) C heat C R R R' H Decolourisation of purple solution with effervescence. Side chain oxidation. Benzoic acid, CO2 and H2O produced. C6H5CH2CH3 + 6[O] ! C6H5COOH + 2H2O + CO2 (R = alkyl) Oxidation. Aldehydes Decolourisation of purple solution. Primary alcohols Secondary alcohols CH3CH2OH + 2[O] ! CH3COOH + H2O (CH3)2CHOH + [O] ! (CH3)2CO + H2O CH3CHO+ [O] ! CH3COOH Side chain oxidation. Benzoic acid, CO2 and H2O produced. O C R R C C6H5COCH3 + 4[O] ! C6H5COOH + H2O + CO2 OH R (R = alkyl) Methanoic acid Ethanedioic acid Decolourisation of purple solution with effervescence. C6H5C(OH)(CH3)2 + 8[O] ! C6H5COOH + 3H2O + 2CO2 Oxidation. These are the only two acids that can be oxidized by KMnO4. HCOOH + [O] ! CO2 + H2O (COOH)2 + [O] ! 2CO2+ H2O Page 27 Reagents Dilute KMnO4 with NaOH(aq) Conditions Functional Group(s) cold Black precipitate of MnO2 formed. C R OH C H CH2=CH2 + H2O + [O] ! CH2(OH)CH2OH (CH3)2CHOH + [O] ! (CH3)2CO + H2O O C R H (R = alkyl or benzyl) heat with immediate distillation Mild Oxidation to produce diols. CH3CH2OH + 2[O] ! CH3COOH + H2O OH R' heat Remarks Oxidation. H H K2Cr2O7 (or Na2Cr2O7) with H2SO4(aq) Purple KMnO4 decolourised. Alkenes R Expected Observation H R C H Orange solution turns greens CH3CHO + [O] ! CH3COOH Note: Oxidation using dichromate(VI) does not affect carbon-carbon double bonds. Oxidation to produce aldehydes. OH CH3CH2OH + [O] ! CH3CHO + H2O Page 28 Reagents Conditions room temp. Functional Group(s) Expected Observation Phenol Phenol and carboxylic acids that are insoluble dissolves in NaOH(aq). Carboxylic acids Remarks Acid-base reaction. C6H5OH + NaOH ! C6H5O–Na+ + H2O CH3COOH + NaOH ! CH3COO–Na+ + H2O Nucleophilic substitution reaction / Hydrolysis. R–X + OH– ! R–OH + X– Halogenoalkanes - (X = Cl, Br or I) To distinguish the different halogenoalkanes, excess HNO3(aq) is added to the resultant solution (to remove the excess NaOH) and AgNO3(aq) added to precipitate the silver halides. White ppt: AgCl | Cream ppt: AgBr | Yellow ppt: AgI Alkaline hydrolysis. Primary amides undergo hydrolysis to give ammonia gas and a carboxylate salt. NaOH(aq) CH3CONH2 + OH– ! CH3COO– + NH3 heat Amides Nitriles Ammonia gas liberated that turns moist red litmus paper blue CH3CN + OH– + H2O ! CH3COO– + NH3 Secondary amides undergo hydrolysis to give amine (may exist as a basic gas when molecule has small no. of carbon atoms) and a carboxylate salt. CH3CONHCH3 + OH– ! CH3COO– + CH3NH2 Confirmatory test for nitriles and amides. Alkaline hydrolysis. Esters - Esters undergo alkaline hydrolysis to give the corresponding carboxylate salt and alcohol (or phenoxide salt). CH3CO2CH3 + OH– ! CH3COO– + CH3OH CH3CO2C6H5 + 2OH– ! CH3COO– + C6H5O– + H2O Page 29 Reagents Conditions Functional Group(s) Expected Observation Remarks Metal-acid reaction to give salt and hydrogen gas. Reactants should be pure and not dissolved in water as that would lead to inaccurate conclusion (H2O reacts with sodium). Alcohols Na(s) - Phenols ROH + Na ! RO–Na+ + ½H2 Effervescence C6H5OH + Na ! C6H5O–Na+ + ½H2 Carboxylic acids RCOOH + Na ! RCOO–Na+ + ½H2 Reaction with sodium must be treated with caution. Acid-base reaction to produce CO2(g). Na2CO3(aq) or NaHCO3(aq) 2CH3COOH + Na2CO3 ! 2CH3COO–Na+ + H2O + CO2 Carboxylic acids - Acid chlorides Effervescence Confirmatory test for carboxylic acids. Acid bromides CH3COCl + Na2CO3 ! CH3COO–Na+ + NaCl + CO2 Acid chlorides can also give carbon dioxide with carbonates. Elimination reaction. Halogen atom and hydrogen atom on adjacent carbon are removed. NaOH (in ethanol) heat Halogenoalkane - CH3 CH3 H C H C H3C H X NaOH (in ethanol) CH3 C H C H H (major) CH2CH3 C C H + NaX + H2O H (minor) (X = Cl, Br or I) May have more than one alkene formed. The more substituted alkene is the major product. Page 30 Reagents Conditions Functional Group(s) Expected Observation - Carboxylic acids - Remarks Acid-base reaction. NH3 CH3COOH + NH3 ! CH3COO– NH4+ Substitution reaction. - Acid chloride Acid bromide White fumes Primary amide is formed. CH3COX + NH3 ! CH3CONH2 + HX (X = Cl or Br) Nucleophilic substitution reaction. Primary amine is formed when excess ammonia is used. CH3Br + NH3 ! CH3NH2 + HBr Concentrated NH3 heat in sealed tube Halogenoalkane - When excess halogenoalkane is used, further substitution may occur that will result in other compounds formed. CH3Br + CH3NH2 ! (CH3)2NH + HBr CH3Br + (CH3)2NH ! (CH3)3N + HBr CH3Br + (CH3)3N ! (CH3)4N+Br– Substitution reaction. ROH + PCl5 ! RCl + POCl3 + HCl PCl5 PCl3 SOCl2 - Alcohols Carboxylic acids RCOOH + PCl5 ! RCOCl + POCl3 + HCl White fumes PBr3 RCOOH + SOCl2 ! RCOCl + SO2 + HCl RCOOH + PBr3 ! RCOCl + POCl3 + HCl Note: PCl5 also reacts with water to form white fumes, hence reaction must be conducted in anhydrous environment. Nucleophilic substitution reaction. KCN (or NaCN) in ethanol heat Halogenoalkanes - CH3CH2X + CN– ! CH3CH2CN + X– (X = Cl, Br or I) Carbon chain increased by one. Page 31 Reagents Conditions Functional Group(s) Expected Observation Remarks Reduction. Phenylamine is formed. Sn with concentrated HCl heat Nitrobenzene - NO2 NH2 + 6[H] 1. Sn with conc. HCl 2. NaOH(aq) + 2H2O Reduction. NaBH4 - Aldehydes Ketones CH3CHO + 2[H] ! CH3CH2OH - (CH3)2CO + 2[H] ! (CH3)2CHOH Reduction. Note: LiAlH4 does not reduce alkenes. CH3CN + 4[H] ! CH3CH2NH2 Nitriles LiAlH4 in dry ether Aldehydes CH3CHO + 2[H] ! CH3CH2OH Ketones (CH3)2CO + 2[H] ! (CH3)2CHOH Carboxylic acids Esters CH3COOH + 4[H] ! CH3CH2OH + H2O Amides CH3COOCH3 + 4[H] ! CH3CH2OH + CH3OH CH3CONH2 + 4[H] ! CH3CH2NH2 + H2O Reduction. CH2=CH2 + H2 ! CH3CH3 Alkenes H2(g) with Ni catalyst high temp. Aldehydes high pressure Ketones Nitriles - CH3CN + H2 ! CH3CH2NH2 CH3CHO + H2 ! CH3CH2OH (CH3)2CO + H2 ! (CH3)2CHOH Note: [H] can be used to replace H2 in equations Page 32 C X C OH H Br2(aq) H R' ü ü ü K2Cr2O7 / H2SO4(aq), heat ü H R C R' O C OH O C Cl O C OR ü ü PCl5 ü ü ü ü ü Fehling’s reagent ü ü ü ü ü « ü ü ü ü « « ü « ü neutral FeCl3(aq) ü ü AgNO3(aq) H2O(l) ü NaOH(aq), heat then test the gas with wet red litmus paper NaOH(aq), heat, acidify with HNO3(aq) followed by AgNO3(aq) ü 1) NaOH(aq), heat, collect distillate ³ 2) Test with K2Cr2O7 / H2SO4(aq) indicates test should not be attempted due to possibility of other undesirable reactions ü indicates positive test primary amides phenylamines ü Na2CO3(aq) or NaHCO3(aq) I2(aq) with NaOH(aq), heat O C NH2 ü Tollens’ reagent Na(s) NH2 ü ü ü ü 2,4-Dinitrophenylhydrazine KMnO4 / H2SO4(aq), heat H O esters C C acid chlorides O carboxylic acids O ketones OH R C OH ü benzaldehydes aldehydes H secondary alcohols primary alcohols CH3 C C phenols Common reagents halogenoalkanes alkenes Functional groups methyl benzenes SUMMARY OF SIMPLE DISTINGUISHING TESTS ü ³ positive iodoform test may be used for esters with –CO2CH(CH3)– structure « indicates that only alcohols with –CH(OH)CH3 group and carbonyl compounds with –COCH3 group can give positive iodoform test STRUCTURE ELUCIDATION Page 33 AMINO ACIDS H They exist as zwitterions H2N H C COOH H3N R COO H2N H3N b g C COO H3N C COO R H2N + Hd d+ C H COO R d+ a-amino acid d- The twenty essential amino acids that make up all the proteins in the body are a-amino acids. The properties of a-amino acids depend on the nature of the R-group. O H ion-dipole interaction They can act as buffer solutions H H2N C H COO OHœ Proteins can be hydrolysed into their constituent a-amino acids by an appropriate enzyme or by acid (or alkaline) hydrolysis. This will cause the peptide bonds to break. H H+ H3N R C COO H3N C R COOH R at high pH net charge = œ1 at low pH net charge = +1 * H R1 O N C C H O N C C H H * H+ heat R1 H2N R2 breaking of peptide bond Formation of proteins n COOH R H H3N CH3 C d+ O CH2 H strong electrostatic attraction d- COOH An a-amino acid is one in which the amino group is joined to the carbon next to the acid group. H R They are readily soluble in water but insoluble in organic solvents C zwitterion H H a R a-amino acid They are crystalline solids with high melting point H C C H R2 COOH H2N C H œH2O COOH * H R1 O N C H C OH– heat R2 O N C H H peptide bond C R1 * n H 3N C H R2 CO O H H 3N C H R2 R1 CO O H H 2N C H CO O H 2N C CO O H Page 34 PROTEINS PRIMARY STRUCTURE It is the composition and sequence of amino acids in its polypeptide chain. This covalent structure is linear, without any branching. amino acids TERTIARY STRUCTURE The polypeptide with its primary and secondary structure can be organized in space to form a more complex polypeptide configuration through the formation of interactions between the R-groups of the amino acids. SECONDARY STRUCTURE It is the arrangement of a polypeptide chain in space around a single axis. It is formed and stabilized by the interactions of amino acids that are fairly close to one another on the polypeptide chain, through hydrogen bonds between the C=O group of one peptide and the N-H group of another peptide. a-helix The hydrogen bonds of the ahelix are parallel to the long axis of the helix. The coiled arrangement of the polypeptide chain forms into a right-handed, spring-like configuration. The R groups in the helical structure point outwards (away from the axis of the helix). These R-groups might interact with other R-groups to stabilize the overall folding of the polypeptide chain in globular proteins by taking part in the tertiary structure. Hydrogen bonding: Hydrogen bonds can also form between amino acid side chains. Interaction between polar R-groups (e.g those with H-bonded to O or N) Disulfide linkages: The –SH side chain of two cysteine can be oxidised to form a covalent disulphide (S–S) bond. These disulphide bonds hold the folded portions of the proteins together with higher integrity, stabilising the specific shape of the protein. b-pleated sheet They can either be parallel or anti-parallel, with adjacent strands being stabilized by hydrogen bonds between N–H and C=O group. Antiparallel b-sheet O H C N C H O H C H C C R N N C C R O H H R O H R H O H R H N C C O C R C N H H O C C H H hydrogen bonding C H H O O H C O N H H N C H C R H N H H N R C R C C H N C H R N R C H O C O R C H N C C C H R N O N C O H C H C N R Parallel b-sheet O C N R Hydrophobic interactions: Proteins often fold to form inner hydrophobic pockets that are stabilised by hydrophobic (van der Waals) forces between uncharged (hydrocarbon) R-groups. These forces stabilise and maintains the 3-D configuration of the protein. Ionic bonds: Electrostatic attraction between acidic and basic groups. The structure of a protein can be stabilized by the force of attraction between amino acid side chains of opposite charge. Page 35 H PROTEINS QUATERNARY STRUCTURE Consists of more than one polypeptide chain coming together to form the complete protein maintained by the same forces that are responsible for tertiary structure. Haemoglobin • • Protein that carries O2 in red blood cells. Consists of four polypeptide chains (two a-sub-units and two b–sub-units), each with an associated haem group. • • Each haem group consists of a central Fe2+ ion that can bond to one O2 molecule. Each haemoglobin is able to carry a maximum of four O2 molecules. FUNCTIONS OF PROTEINS • • • • Enzymes (act as biological catalysts) Antibodies (produced by immune system in response to foreign antigens) Transport proteins (carry materials from one place to another in the body) Regulatory proteins (control cell functions) • • Structural proteins (provide the framework which defines the size and shape of cells) Movement proteins (for all forms of movement using muscle fibres, through interaction of actin and myosin proteins) • Nutrient proteins (a source of amino acids) DENATURATION OF PROTEINS • Highly organized structure of proteins becomes completely disorganized. • Quaternary, tertiary and secondary protein structures break down resulting in the protein unfolding to give a randomly coiled polypeptide. • • • Primary structure of the protein remains unaffected. Leads to the loss of their biological activity. Often leads to irreversible changes in their physical and chemical properties (e.g decrease in solubility). FACTORS LEADING TO PROTEIN DENATURATION Heat pH changes Heavy metal ions Oxidizing / Reducing agents Hydrogen bonding Ionic interactions Hydrophobic interactions Disulphide linkages relatively weak interactions, easily destroyed by heat depends on temperature relatively weak interactions, easily destroyed by heat depends on temperature depends on which functional group the H-bonding is found protonation or deprotonation will occur destroying existing electrostatic interactions not affected not affected not affected they interfere with electrostatic attractions present not affected they react with disulphide bridges to form precipitates not affected not affected not affected reducing agents break disulphide bridges Page 36