Aldehydes, Ketones and Carboxylic Acids PDF

ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids...

ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Smart Booklets 8 Aldehydes, Ketones & Carboxylix Acids Aldehydes Aldehydes and ketones contain carbonyl [ C O ] group and are collectively known as carbonyl compounds. In aldehydes, carbonyl carbon atom is bonded atleast with one hydrogen atom. Thus general formula of aldehydes is R−CHO and functional group is −CHO. [R=H, alkyl, aryl, aralkyl, alkenyl, cycloalkyl etc.] The saturated open chain aliphatic aldehydes are called alkanals and form a homologous series with general formula CnH2nO. H H H H R C O Ex. H C O CH3 C O CH2 C O R= H, alkyl or aralkyl formaldehyde acetaldehyde phenylacetaldehyde While in aromatic aldehydes, carbonyl carbon atom of −CHO group is directly linked to benzene ring. First member of aromatic aldehydes is benzaldehyde and other members are its derivatives. O HO O O O H2N C CH3O C C H C H H H HO benzaldehyde salicylaldehyde m-aminobenzaldehyde vanillin Ketones In ketones, carbonyl group is bonded with two alkyl or aryl groups or both and the general formula is RCOR . Dialkyl ketones are functional isomers of aliphatic aldehydes with general molecular formula CnH2nO. In aliphatic ketones, carbonyl group is bonded with two alkyl groups whereas, in aromatic ketones carbon atom of keto group is bonded to benzene ring. Depending upon the nature they are classified as simple and mixed ketones. In case of simple or symmetrical ketones, carbonyl group is bonded with identical groups (R = R ). O O CH3 C CH3 C acetone benzophenone While in mixed ketones, carbonyl group is linked with two different alkyl groups or aryl groups or both. ( R  R ) O O C CH3 CH3 C CH2 CH3 ethylmethyl ketone acetophenone 93 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Nomenclature of aldehydes Aliphatic aldehydes are named by IUPAC system by changing the terminal ‘e’ of the parent hydrocarbon to −al. Hence, IUPAC name of aldehydes is alkanal. In higher aldehydes, the parent chain is numbered by assigning number 1 to the aldehydic carbon atom. Example Common name IUPAC name O Formaldehyde Methane − e + al = Methanal H C H O Acetaldehyde Ethane − e + al = Ethanal CH3 C H CH3−CH2−CHO Propionaldehyde Propane − e + al = Propanal CH3−CH2−CH2−CHO Butyraldehyde Butanal CH3 CH CHO Isobutyraldehyde 2-methylpropanal CH3 CH 2 = CHCHO Acrolein Prop-2-en-al CH 3 CH = CHCHO Crotonaldehyde But-2-en-1-al C 6 H 5 CH = CHCHO Cinnamaldehyde 3-phenylprop-2-en-1-al O O Glyoxal Ethane-1,2-dial H C C H CHO benzaldehyde benzenecarbaldehyde or phenylmethanal Nomenclature of ketones O They are represented by the general formula, R C R where R and R are alkyl or aryl group. If R and R are the same, then such ketones are called simple ketones or symmetrical ketones. If R and R are different, then such ketones are called mixed ketones or unsymmetrical ketones. In trivial system, the substituents attached to the carbonyl group are named in the alphabetical order followed by ketone. Ketones are named in the IUPAC system by changing the terminal ‘−e’ of the parent alkane to ‘−one’. Hence, the IUPAC name of ketones is alkanone. In higher ketones the carbon chain is numbered from the end nearer to the ‘keto’ group. Example Common name IUPAC name CH3COCH3 dimethyl ketone (acetone) Propane − e + one = Propanone CH3CH2COCH3 ethyl methyl ketone Butane − e + one = Butanone 1 2 3 4 5 C H3 C H2 C O C H2 C H3 diethyl ketone 3-pentanone (or) Pentan-3-one 1 2 3 4 5 Metamers C H3 C O C H 2 C H 2 C H 3 methyl propyl ketone 2-pentanone (or) Pentan-2-one (C5H10O) 94 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids 4 3 2 1 CH3 CH CO CH3 methyl isopropyl ketone 3-methylbutanone (or) CH3 3-methylbutan-2-one 1 2 3 4 5 CH3 CH CO CH CH3 disopropyl ketone 2,4-dimethyl-3-pentanone (or) CH3 CH3 2,4-dimethylpentan-3-one O O methyl glyoxal 2-oxopropanal 2 1 CH3 C CHO CO CH3 methyl phenyl ketone Acetophenone or 1-phenylethanone CO diphenyl ketone benzophenone Isomerism in Aldehydes and Ketones In addition to chain and position isomerisms aldehydes and ketones show functional isomerism. It is important to note that alkanal, alkanone, alkenol, alkoxyalkane, cycloalkanol and cyclic ethers are functional isomers with molecular formula CnH2nO. For example, structure of isomers with molecular formula C3H6O are as follows. CH CH CHO CH COCH CH CHCH OH CH OCH CH 3 2 3 3 2 2 3 2 propanal propanone allyl alcohol methoxyethene O O OH CH3 cyclopropanol oxitane methyloxirane Ketones show metamerism in which isomers differ in the alkyl groups around carbonyl group. CH3COCH2CH2CH3 CH3CH2COCH2CH3 2-pentanone 3-pentanone General Methods of Preparation The following methods are employed for the synthesis of aliphatic aldehydes and ketones. 1. From alkenes Reductive ozonolysis of alkenes gives corresponding carbonyl compounds. O O (i) O3 R + R (ii) H2O/Zn R H R H H 2O 2 R O O R (i) O3 R + (ii) H2O/Zn R R R H H2O2 ketone aldehyde R O O R (i) O3 R R R + (ii) H2O/Zn R R R H 2O 2 ketones 95 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids 2. From alkynes Hydration of alkynes yields carbonyl compounds. (a) Borohydration followed by oxidation with hydrogen peroxide in alkali of acidic alkynes yields aldehydes. Sia2BH H2O2/HO R C C H RCH CH [R CH CH] R CH2 CHO acidic alkyne OH aldehyde BSia2 Sia2BH is bis secondary isoamylboronohydride (b) Acid catalysed hydrolysis of alkynes gives ketones. O Hg(SO4) / dil. H2SO4 R C CH + H2O [R C CH2] [R C CH3] 70o C OH ketones 3. From Alcohols Aldehydes and ketones are conveniently prepared by the oxidation of primary and secondary alcohols. Oxidation of alcohols Aldehydes are obtained by the oxidation of primary alcohols using acidified potassium dichromate, potassium permanganate, etc. However, the oxidation proceeds further to give carboxylic acids. One way of overcoming this problem is to remove the aldehyde by distillation as soon as it is formed, since aldehydes have lower boiling points than the corresponding alcohols. (K2Cr2O7 + dil H2SO4) [O] RCH2OH + [O] RCHO RCOOH heat/-H2O 1o alcohol aldehyde carboxylic acid (K2Cr2O7 + dil H2SO4) CH3CH2OH + [O] CH3CHO + H2O heat ethyl alcohol acetaldehyde CH2OH (K2Cr2O7 + dil H2SO4) CHO + [O] + H2O heat benzyl alcohol benzaldehyde In aqueous medium aldehydes are more susceptible for oxidation than alcohols with the result, the yield of aldehydes is low. The primary.. alcohols are oxidised to aldehydes by treating pyridinium + chlorochromate (C5 H5NH.OCrO2Cl) in methylene chloride (CH2Cl2). It is abbreviated as PCC and called Collin reagent. This is a selective reagent because it checks further oxidation of aldehydes to carboxylic acids. Ketones are obtained by the oxidation of secondary alcohols using acidified K2Cr2O7 or alkaline KMnO4. The reaction usually stops at the ketone stage because further oxidation brings about the breaking of C−C bond. (K2Cr2O7 + H2 SO4) RCHOHR + [O] RCOR + H2O heat 2o alcohol ketone 96 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (K2Cr2O7 + H2SO4) CH3CHOHCH3 + [O] CH3COCH3 + H2O heat 2-propanol (isopropyl alcohol) propanone (acetone) High yield of ketones is obtained by this method. Solution of chromic anhydride (CrO3) in water, acetone and sulphuric acid is called Jone’s reagent which is the most effective oxidizing agent for the preparation of ketones from 2 alcohols. Secondary alcohols are also oxidised to corresponding ketones by heating with aluminium t-butoxide in acetone. It is called Oppenauer oxidation. [(CH3)3CO]3Al RCHOHR + CH3COCH3 RCOR + CH3CHOHCH3 Al(tBuO)3 Dehydrogenation of alcohols When the vapours of alcohols are passed over preheated copper at about 570 K, dehydrogenation occurs forming aldehydes and ketones from corresponding primary and secondary alcohols respectively. It is -elimination reaction. H Cu / 570 K R CH O H R C O + H2 H aldehyde 1o alcohol Cu / 570 K CH3CH2OH CH3CHO + H2 ethyl alcohol acetaldehyde Cu / 570 K C6 H5CH2OH C6 H5CHO + H2 benzyl alcohol benzaldehyde R R Cu / 570 K R C O H R C O + H2 H 2o alcohol Cu / 570 K CH3CHOHCH3 CH3COCH3 + H2 isopropyl alcohol acetone Cu / 570 K C6 H5CHOHCH3 C6 H5COCH3 + H2 1-phenyl-1-ethanol acetophenone 4. From Acid Chloride, Esters and Nitriles The carboxylic acid derivatives can be reduced to corresponding aldehydes by using mild reducing agents like lithium tri-tertbutoxy aluminium hydride (LBAH) and diisobutyl aluminium hydride (DBAH). These two hydrides are less reactive than LiAlH4 as they are sterically hindered. O H OAl(iBu)2 HO OH O H3O + R O + (iBu)2AlH O R H R heat R H H2O 97 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (i) (iBu)2AlH H CN (ii) H2O O O O (i) (iBu)2AlH Cl (ii) H2O H Acid chlorides can be reduced to corresponding aldehyde by heating with hydrogen in presence of Lindlars’ catalyst. It is called Rosenmund reduction reaction. O O Pd-BaSO4 R Cl + H2 R H + HCl heat Nitrile is dissolved in ether and reduced with stannous chloride and hydrochloric acid. The iminochloride thus formed when hydrolysed with water yields aldehyde. (SnCl2 + HCl) H2O R C N + 2[H] RCH NH.HCl R CHO + NH4Cl heat Here, H2[SnCl4] is formed, which is a strong reducing agent. This reaction is called Stephens’ reduction. The ketones are obtained by the action of organometallic compounds on derivatives of carboxylic acids followed by hydrolysis. O (i) ether R C N + R MgX R C R + Mg(OH)X (ii) H3O + O (i) ether/heat R C N + RLi R C R (ii) H3O + O O Et (i) ether/heat O + R Li R C R R (ii) H3O + O O Et (i) ether/heat O + R MgX R C R R (ii) H3O + O O ether R C Cl + R Li R C R + LiCl O O ether 2R C Cl + R2Cd 2R C R + CdCl2 O O (i) ether R C Cl + R2CuLi R C R + R Cu + LiCl (ii) H3O + 5. From Calcium Salts of Carboxylic Acids Aldehydes are obtained by the dry distillation of calcium salt of a carboxylic acid with calcium formate. However, calcium formate alone on dry distillation gives formaldehyde (methanal). 98 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids O H C O O dry distillation Ca H C H + CaCO3 H C O formaldehyde O calcium formate When an equimolar mixture of calcium carboxylate and calcium formate is dry distilled, an aldehyde except formaldehyde is formed. O O O R C O O C H dry distillation Ca + Ca 2R C H + 2 CaCO3 R C O O C H aldehyde O O dry distillation (CH3COO)2Ca + (HCOO)2Ca 2CH3CHO + 2CaCO3 calcium acetate calcium formate acetaldehyde dry distillation (C6 H5COO)2Ca + (HCOO)2Ca 2C6H5CHO + 2CaCO3 calcium benzoate benzaldehyde This method is not suitable for the preparation of aldehydes except formaldehyde as the yield of the desired aldehyde is low. This is due to the fact that when a mixture of two calcium salts of carboxylic acids is distilled, three products are formed. For example, dry distillation of a mixture of calcium formate and calcium acetate gives formaldehyde, acetaldehyde and acetone. The symmetrical (simple) ketones are obtained by dry distillation of calcium salt of carboxylic acids other than formic acid. O O R C O dry distillation Ca R C R + CaCO3 R C O ketone O calcium carboxylate dry distillation (CH3 COO)2 Ca CH3 COCH3 + CaCO3 calcium acetate acetone dry distillation (C6 H5COO)2Ca C6 H5COC6 H5 + CaCO3 calcium benzoate benzophenone This method cannot be used for the synthesis of unsymmetrical ketones since it gives a mixture of three ketones when an equimolar mixture of two calcium salts of carboxylic acids is subjected to dry distillation. Five or six membered cyclic ketones are obtained in good yield when calcium salts of corresponding dicarboxylic acids are dry distilled. CH2 CH2 COO dry distillation Ca O + CaCO3 CH2 CH2 COO calcium hexanedioate cyclopentanone 99 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids CH2 CH2 COO dry distillation O H2C Ca + CaCO3 CH2 CH2 COO calcium heptanedioate cyclohexanone Synthesis of Aromatic Carbonyl Compounds 1. From methyl arenes Methyl arenes can be converted into aldehyde by the following reagent. CrO2Cl2/CCl4 CHO + H2O (Etards' reaction) heat CH3 CHO air(O2)/MnO toluene + H2O 500oC 2. Guttermann Koch formylation When aromatic hydrocarbons or halobenzenes are heated with carbon monoxide and hydrogen chloride in presence of anhydrous zinc chloride, aromatic aldehyde is formed. O anhy.ZnCl2 C H + [CO + HCl] + HCl heat Since formyl chloride (HCOCl) is unstable, formyl groups (−CHO) can be introduced in the form of (CO + HCl) or (HCN + HCl). Formyl carbocation is formed as follows. + CO + HCl + AlCl3 H C O + AlCl4 3. Guttermann formylation When benzene or aromatic compounds containing activating groups (like −OH, −OR etc) is heated with a mixture of hydrogen cyanide and hydrogen chloride in presence of anhydrous ZnCl 2 or AlCl3, corresponding aromatic aldehyde is obtained. The reaction is called Guttermann formylation. AlCl3 H C N + HCl Cl CH NH AlCl3 CH NH H 2O CHO + Cl CH NH + NH3 ether/heat 4. Friedel-Craft acylation O AlCl3 C CH3 + CH3COCl + HCl ether/heat O O C Cl AlCl3 C + + HCl ether/heat 100 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids For preparation of ketones of the type ArCOAr/ if one of the aryl groups contain deactivating substituent it should be present in acid chloride moiety. O O Cl AlCl3 + + HCl heat NO2 NO2 Nitrobenzene and benzoyl chloride cannot be used because strongly deactivating nitro group prevents the acylation. Physical properties of aldehydes and ketones (i) Most of the aldehydes are liquids at room temperature except formaldehyde, which is a gas. Lower ketones are colourless liquids with pleasant smell, while higher members of ketones are solids. (ii) Aldehydes and ketones have relatively high boiling points as compared to hydrocarbons of comparable molar mass due to the presence of polar carbonyl group which results in stronger intermolecular dipole- dipole interactions. (iii) However these dipole-dipole interactions are weaker than intermolecular hydrogen bonding in alcohols. Hence, the boiling points of aldehydes and ketones are relatively lower than the alcohols of comparable molecular mass. (iv) The lower members of aldehydes and ketones such as methanal, ethanal and propanone are miscible with water in all proportions. This is due to the formation of hydrogen bond with water. The solubility in water decreases with increase in the size of the alkyl groups due to larger non-polar character. Chemical Properties The carbon atom of carbonyl group is sp2 hybridised with a trigonal planar geometry. The carbon-oxygen double bond is polarized due to high electronegativity of oxygen. The electrophilicity (electron deficiency) of a carbonyl group derives from resonance effect reinforced by inductive effect. +.. C O C O The carbonyl group governs the chemical reactions of aldehydes and ketones by providing a site for nucleophilic addition and by increasing the acidity of hydrogen atoms bonded to -carbon. These characteristic reactions are due to the ability of oxygen to accommodate the negative charge. 1. Nucleophilic Addition When reagent is a strong nucleophile, the addition takes place in the following ways in which planar carbonyl group is converted into a tetrahedral product. Nu Nu R.. H2O C O + Nu C O.. C OH R R R R R The ability of oxygen to carry negative charge is the cause of the reactivity of carbonyl group toward nucleophiles. 101 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids The addition reaction is acid catalysed when the attacking reagent is a weak nucleophile. The addition on carbonyl group takes place in the following way. R H.. Nu R.. + Nu C..O + H C O + C O H R R R R oxonium ion The oxonium cation is highly reactive towards nucleophile as carbonyl carbon atom is highly electron deficient than unprotonated molecule. Prior protonation of the carbonyl group lowers the activation energy (Ea) for nucleophilic attack. This mechanism operates when carbonyl compounds are treated with strong acid (including Lewis acids) and weak nucleophiles like water, alcohols etc., Relative reactivity towards nucleophilic addition The relative reactivity of aldehydes and ketones towards nucleophilic addition reactions depends upon following factors. Steric factor The bulky substituents on carbonyl carbon cause steric hindrance for nucleophilic attack and reactivity towards nucleophilic addition decreases. Higher the steric effect, lesser the reactivity and order of reactivity of certain carbonyl compounds is given. HCHO > CH3CHO > (CH3)2CHCHO > (CH3)3CCHO > CH3COCH3 > C6H5COCH3 > C6H5COC6H5. Electronic factor Higher the magnitude of electron deficiency on the carbonyl carbon atom greater the reactivity towards nucleophilic addition reactions. Thus electron withdrawing group increases the reactivity while the electron releasing group on carbonyl carbon atom decreases the reactivity. The order of reactivity of certain carbonyl compounds are given O2NCH2CHO > ClCH2CHO > CH3CHO > C6H5CHO -I effect I effect + I effect R effect The participation of phenyl group in resonance decreases electron deficiency on carbonyl carbon and deactivate the nucleophilic addition. (i) Hydration (gem diol formation) Aldehydes and ketones react with water in presence of acid or base in a rapidly reversible equilibrium. R R OH C O + H2O C R R OH gem diol Hydration of carbonyl compounds follows the order. O O O > > H > H H H O % of hydration : 99.96 50 19 0.14 102 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Hydration takes place readily if the gem diol is stabilised by intramolecular hydrogen bonds. The gem H diol of chloral is stable. Cl O Cl C C H Cl O (chloral hydrate) H (ii) Addition of alcohol (Acetal formation) Alcohol molecules add to the carbonyl group in presence of dry HCl to form acetals. R R OH ROH/H+ R OR H+ C O + ROH C C R H2O R R OR OR hemiacetal acetal The steps involved in the formation of acetals from aldehydes are reversible. Open chain hemiacetals are unstable while cyclic five and six membered rings are stable. Acetal formation is less favoured when ketones are treated with monohydric alcohols in presence of dry hydrogen chloride. However, cyclic acetal formation is favoured when ketones are treated with glycol and a trace of acid. R HO CH2 R O R H+ H3O + CH2OH C O + C C O + HO CH2 H2O R CH2OH R R O cyclic acetal This reaction is used to protect carbonyl group. O O OH O [H] OH H3O+ OH O O O O O OH H+ LAH O O (iii) Addition of hydrogen cyanide The addition of HCN to carbonyl group of aldehydes or ketones gives corresponding cyanohydrin. R R OH C O + HCN C R R CN cyanohydrin Since HCN is toxic, volatile and a weak acid, it is generally produced in the reaction mixture for which strong acid (HCl or H2SO4) is added to a solution of aldehyde or ketone and NaCN or KCN. The cyanohydrins are useful intermediate in organic synthesis. O H3O+/boil OH O OH HO CN (i) NaCN(aq)/ether -hydroxy carboxylic acid (ii) dil HCl 2-butanone [H] LiAlH4 / H2O NH2 OH -amino alcohol Benzophenone does not react with HCN as carbonyl group is sterically hindered. 103 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (iv) Addition of sodium bisulphite Aldehydes aliphatic methyl ketones and cyclic ketones react with sodium bisulphite solution to give white solid of bisulphite adduct. O OH R C H + NaHSO3 R C H SO3 Na sodiumbisulphite adduct (white solid) Sterically hindered aromatic ketones such as C6H5COCH3, C6H5COC6H5 etc., do not respond to this reaction. The order of reactivity is HCHO > CH3CHO > PhCHO > CH3COCH3 > CH3COCH2CH3 (v) Reaction with ammonia Aliphatic aldehydes except formaldehyde react with ammonia forming white solid of addition product called aldehyde ammonia adduct. H3O+ + CH3 CHO + HNH2 CH3CH OH CH3 CHO + NH4 heat ammonia NH2 (vi) Addition of Grignard reagent Addition of RMgX to carbonyl group followed by hydrolysis gives corresponding alcohols. O OMgX OH ether H2O R C R + RMgX R C R R C R + Mg(OH)X R R alcohol 2. Condensation Reactions (Reaction with Ammonia Derivatives) The condensation reactions of ammonia derivatives (H2N−G; G = −OH, −NH2, −NHR, −NHCONH2, −NHCONHNH2, etc) are catalysed by an acid and involve two steps, nucleophilic addition of ammonia derivative to form carbinol amine followed by dehydration to yield imine. H + H NHG NG R.. R + NH2 G R H+ C.. O C O R C OH R C OH C NG H+ H2O R R H R R R carbinol amine imine The imine formation requires moderate pH(4 − 5), imine protonation of ammonia derivatives take place at low pH and the addition reaction retards at high pH. The following reactions illustrate condensation reactions of ammonia derivatives. R R C O + H2N NH2 C N NH2 + H2O R hydrazine R hydrazone R R C O + H2N NHPh C N NHPh + H2 O R R phenylhydrazone 104 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids H H R R C O + H2 N N NO2 C N N NO2 + H2O R R NO2 NO2 2,4-dinitrophenylhydrazine (2,4-DNP) (orange solid) Bradys' reagent This reaction is employed as a qualitative test for aldehydes and ketones. O O R R C O + H2N NH C NH2 C N NH C NH2 + H2O R R semicarbazide semicarbazone O O R R C O + H2NNHCNHNH2 C NNHCNHNH2 + H2O R R carbazide carbazone Thiosemicarbazones and thiocarbazones are formed from the thiosemicarbazide and thiocarbazides respectively. R R C O + H2N OH C NOH + H2O R hydroxyl amine R oxime Ph Ph C O + H2N R C N R + H2O R 1o amine R Schiffs' base 3. Oxidation Reactions i. Reactions due to H of CHO group (Reducing properties of aldehydes) The aldehydes are easily oxidised to carboxylic acids containing same number of carbon atoms. This is due to the fact that the hydrogen atom of carbonyl group is easily converted into carboxylic group without involving the cleavage of other bonds. The following reaction accounts for the reducing properties of aldehydes. RCHO + [O] → RCOOH Thus, aldehydes act as reducing agents and reduces Tollen’s reagent, Fehling’s solution, Benedict’s reagent, etc. The following reactions are characteristics of aldehydes, employed as qualitative tests and also used to distinguish aldehydes from ketones. Reaction with Tollens’ reagent When aldehydes are heated with Tollen’s reagent (ammoniacal silver nitrate), a bright silver mirror is produced. ammoniacal RCHO + Ag2O 2Ag + RCOOH heat silver mirror Ketones do not react with Tollen’s reagent, however, -hydroxy ketones (−COCH2OH) respond to Tollen’s test. 105 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Preparation of Tollens’ reagent A drop of NaOH solution is added to AgNO3 solution to form grey precipitate of silver oxide. To the resulting precipitate, ammonium hydroxide is added till it just dissolves and the clear solution is called Tollen’s reagent. 2NH4OH 2AgNO3 + 2NaOH [2AgOH] Ag2O 2[Ag(NH3)2]OH NaNO3 H2O grey ppt. H2O white ppt. Tollens' reagent RCHO + 2[Ag(NH3)2]OH 2Ag + RCOOH + H2O + 4NH3 heat Silver mirror Fehlings’ reaction When aldehydes are heated with Fehling’s reagent, red precipitate of cuprous oxide is formed. alkaline RCHO + 2CuO Cu2O + RCOOH heat red ppt. Fehling’s reagent is alkaline solution of copper sulphate containing sodium potassium tartarate (Rochelle salt). Aromatic aldehydes with no -hydrogen do not respond to this reaction as they are rapidly converted into corresponding sodium salts of carboxylic acids and alcohols. (Cannizzaros’ reaction). Aldehyde containing -hydrogen reduce Benedicts reagent to red precipitate of cuprous oxide. Benedicts reagent is a deep blue aqueous solution containing copper sulphate sodium citrate and sodium hydroxide. This reaction is not answered by aldehyde with no -hydrogen. The Tollen’s and Fehling’s reactions are employed as qualitative tests for aldehydes. Schiffs’ test Aldehydes restore pink colour of Schiffs’ reagent. Schiffs’ reagent is rosaniline hydrochloride dissolved in hydrochloric acid and solution is decoloured by treating with sulphur dioxide.  or - hydroxyl aldehydes do not respond to Schiffs’ test as they exist in cyclic hemiacetal form. ii. Oxidation of aldehydes Aldehydes can be easily oxidized to corresponding monocarboxylic acids by heating with common oxidising agents like acidified potassium dichromate or potassium permanganate. (K2Cr2O7 + dil.H2SO4) RCHO + [O] CH3COOH heat aldhyde (K2Cr2O7 + dil.H2SO4) CH3CHO + [O] CH3COOH heat Aromatic aldehydes readily get oxidized to carboxylic acids by heating with alkaline potassium permanganate followed by acidification. alkaline KMnO4 dil.HCl C6 H5CHO + [O] C6 H5COONa C6 H5COOH heat NaCl iii. Oxidation with sodium hypohalide (Haloform reaction) Methyl ketones when heated with iodine solution and sodium hydroxide, pale yellow solid of iodoform and sodium salt of carboxylic acid are formed. This reaction is called iodoform reaction. O heat R C CH3 + 4NaOH + 3I 2 RCOONa + CHI 3 + 3NaI + 3H2O methyl ketone 106 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids This reaction is one of the best methods for the conversion of methyl ketones into carboxylic acids. The iodoform reaction is used as qualitative test for methyl ketones or compounds which yield such products on oxidation with NaOH and iodine. 4. Reduction Reactions of Aldehydes and Ketones i. Reduction carbonyl group to alcohols Aldehydes and ketones can be reduced to primary and secondary alcohols respectively by a variety of reagents. The catalytic hydrogenation of carbonyl compounds gives alcohol. OH R Ni/heat C O + H2 R CH R R Along with carbonyl group of aldehydes or ketones, other groups such as CC, C=C, −COOR, −COCl, etc., and also reduced. Lithium aluminium hydride (LiAlH4) and sodium borohydride (NaBH4) reduce aldehydes or ketones o corresponding alcohols. The reduction of carbonyl group involves nucleophilic addition followed by hydrolysis with dilute HCl or NH4Cl solution. 3R2CO NH4Cl(aq) R2C O + [H AlH3]Li R2CHOAlH3 (R2CHO)4 Al 4R2CHOH + [Al(OH)4] LiAlH4 is less selective and reduces other groups like ester, anhydride, acid chloride to alcohol along with carbonyl group of aldehyde or ketone. O OH (i) LiAlH4 O (ii) H2O O OH Sodium borohydride (NaBH4) is highly selective in reducing more reactive carbonyl group of aldehydes or ketones. The reducible groups such as −COOH, −COOR, −CO−O−CO−, C=C, etc., are not reduced. O OH O OH (i) NaBH4 O (i) NaBH4 O ; (ii) NH4Cl(aq) (ii) H2O/H+ O O Meerwein Ponndorf Verley (MPV) reduction The reduction of carbonyl compounds to alcohols by employing aluminium isopropoxide in isopropyl alcohol is called MPV reaction. O OH OH (iPrO)3Al + ; (iPrO)3Al = O Al  3 It is a selective reduction, the reducible groups such as −NO2, C=C, −CC−, −COOR, etc., are not affected. 107 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids ii. Reduction of carbonyl group to methylene group Clemmensen reduction The reduction of aldehydes and ketones to the corresponding hydrocarbon by using zinc amalgam and concentrated hydrochloric acid is called Clemmensen reduction. O R C R + 4[H] R CH2 R + H2O The reaction is selective for carbonyl group of aldehydes and ketones and does not affect the carbonyl group of a carboxylic acid. O OH OH (ZnHg) + conc HCl) + 4[H] O heat O 3-methyl-4-oxophenylbutanoic acid 3methyl-4-phenylbutanoic acid If compound contains nitro group (−NO2), it is reduced to amine (−NH2). This reduction involves a transfer of electrons from metal and protonation of intermediate species by strongly acidic reaction mixture. The mechanism is complex and not completely understood. This reduction is applicable to ketones as yield of product is low in aldehydes. Wolff Kishner reduction When ketones are heated with hydrazine in alkaline medium, carbonyl group is reduced to methylene group forming corresponding hydrocarbons. This reduction reaction is called Wolff Kishner reaction. O H2N-NH2/HO R C R + 4[H] RCH2R + H2O heat ketone 5. Reactions involving -hydrogen of carbonyl group The carbonyl compounds exhibit unusual acidity of -hydrogen as its conjugate base is stabilized by resonance. O O O.. C C R C C B.. + H BH C.. R C R carbanion enolateion O H −hydrogen; pKa = 40 - 50 R H  −hydrogen; pKa = 19 - 20 Thus the susceptibility to nucleophilic attack and the acidity of -hydrogen of carbonyl group is due to the ability of oxygen to accommodate the negative charge. (i) Aldol reaction : Two molecules of an aldehyde or a ketone containing one or more -hydrogen atoms when treated with dilute solution of base (like NaOH, Ba(OH)2, K2CO3, etc) at room temperature, -hydroxyl aldehyde or ketones are formed. This reaction is called aldol reaction. O.. HO O HO 2 H H acetaldehyde 3-hydroxybutanal (alcohol) 108 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids HO(aq).. 2 H H heat H HO O H2O O O.. HO(aq) 2 H2O O OH O O In some cases, when double bond is in conjugation with aromatic ring, dehydration of aldol readily takes place. With the result, the product aldol cannot be isolated. O OH O O EtONa/ Ph Ph Ph 2 Ph EtOH Ph H2O aldol Dypnone Acid catalysed aldol reaction Aldol condensation can also be brought about with acid catalyst. Acetone when treated with dry HCl gives mesitylene oxide (4-methyl-3-penten-2-one). O O OH O O O OH dry HCl 2 H 2O cross aldol mesitylene oxide H2O O phorone Acetone on distillation with concentrated sulphuric acid gives mesitylene (1, 3, 5-trimethylbenzene). O conc.H2SO4 3 + 3H2O distillation mesitylene (ii) Cross aldol reaction: An aldol reaction between two different carbonyl compounds each having at least one -hydrogen is called cross aldol reaction. A mixture of two carbonyl compounds gives four aldol products. For example, reaction of acetaldehyde and propanal in presence of dilute sodium hydroxide solution gives four products. O HO O H (aldol reaction) O HO.. O H H H2O.. H H (cross aldol) H OH O O O OH O H (cross aldol) H H HO.... H O H2O H O (aldol reaction) H HO O O 109 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (iii) Intramolecular aldol reaction A dialdehyde, a keto-aldehyde or a diketone undergoes aldol reaction to form five or six membered (sometimes even longer) cyclic compounds. O.. O OH O O HO.. HO.. O H H H2O.. H2O O O heat H2O O The higher reactivity of aldehyde group towards nucleophilic addition than keto group is due to electronic as well as steric factors. (iv) Aldol related reactions A few condensation reactions closely related to aldol reaction which involve attack of carbanion on carbonyl group followed by elimination of simple molecule to form , -unsaturated products are discussed. Claisen Schmidt reaction A cross aldol reaction in which an aromatic aldehyde reacts with an enolisable aldehyde or ketone to form ,-unsaturated carbonyl compounds is called Claisen Schmidt reaction. O O.. HO(eq) O Ph H + R Ph R + H2O ,-unsaturated carbonyl compound O O.. HO(eq) O Ph H + H Ph H + H2O cinnamaldehyde 6. Reactions of Aldehydes with no -hydrogen (i) Cannizzaro reaction: Aldehydes containing no -hydrogen when treated with concentrated aqueous or alcoholic alkali, self redox reaction takes place forming an equimolar mixture of alcohol and salt of carboxylic acid. It is a disproportionation called Cannizzaro reaction. This reaction is carried out at room temperature. 50% NaOH 2HCHO + NaOH HCOONa + CH 3OH H 50% alkali ONa OH 2 + NaOH + O O O O 50% alkali + NaOH Ph ONa + Ph OH 2Ph H 2-methylpropanal also undergoes Cannizzaros’ reaction in concentrated NaOH solution along with aldol reaction. H 50% alkali ONa OH 2 + NaOH + O O 110 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (ii) Cross Cannizzaro reaction Cannizzaro reaction between two different aldehyde molecules is known as cross Cannizzaro reaction. 50% alkali PhCHO + HCHO + NaOH Ph OH + HCOONa Formaldehyde is susceptible to oxidation hence, oxidised to sodium formate. (iii) Intramolecular Cannizzaro reaction Dialdehyde and ketoaldehyde undergo intramolecular (internal) Cannizzaro reaction. CHO COONa + NaOH CHO CH2OH O OH H + NaOH ONa Ph Ph O O The keto group gets reduced to alcohol while aldehyde is oxidized in internal Cannizaro reaction. CHO CH2OH (i) NaOH CHO (ii) H+ COOH Since the base is consumed in the reaction, usually about 50% strength of alkali is used. This contrasts with the catalytic role that the base plays in aldol and related condensations. Preparation of pentaerythritol from acetaldehyde and formaldehyde utilises both the crossed aldol and crossed Cannizzaro reactions. This is shown below: CH2OH CH2OH Alkali CH2O CH3CHO + 3CH2O HOH2C C CHO (higher concentration HOH2C C CH2OH + HCOOH (catalytic quantity) CH2OH of alkali ) CH2OH pentaerythritol The carbonyl group gets reduced to alcohol while formaldehyde is oxidised in cross Cannizaro reaction. (iv) Benzoin condensation: Aromatic aldehydes when heated with alcoholic KCN, benzoin is formed. O OH KCN Ph 2Ph H alcohol/heat Ph O benzaldehyde benzoin 7. Special reactions of carbonyl compounds Lower aldehydes or ketones undergo autopolymerisation reaction or copolymerisation reaction. Formaldehyde evaporation [n = 10 - 60] (a) nHCHO HOCH2(OCH2)nCH2OH HO O O O OH formaline white solid (mp 123oC) para formaldehyde O (b) 3HCHO (HCHO)3 or O O meta formaldehyde (trioxane) m.p. 61 oC 111 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Diagnostic tests for aldehydes and ketones Tollens’ test Aldehydes with -H and terminal -hydroxy ketones deposit a silver mirror along the sides of the test tube when treated with ammonical AgNO3. -hydroxy ketones tautomerise to the corresponding aldehyde, which actually answers the test. Fehlings test Aldehydes give a reddish brown precipitate of Cu2O when treated with CuSO4 dissolved in aqueous sodium potassium tartrate in alkali medium. -hydroxy ketones also answer this test. Benedicts test This is essentially Fehlings test except that the reagent is prepared in sodium citrate in place of tartrate and sodium carbonate in place of NaOH. Schiff’s test Aldehydes restore the magenta colour of Schiff’s reagent, which is rosaniline hydrochloride dissolved in water and decolourised with SO2 gas. Iodoform test Yellow precipitate of iodoform is obtained with methyl ketones when treated with alkali and iodine. Among aldehydes, acetaldehyde answers this test. Bisulphite test Aldehydes, methyl ketone and some cyclic ketones give a white precipitate of the adduct, when shaken vigorously with a saturated aqueous solution of NaHSO3. 2, 4-DNP test Aldehydes and ketones give orange/red precipitate of 2,4-dinitrophenylhydrazone when treated with 2,4-DNP dissolved in acidified ethyl alcohol. Similarly, oximes from hydroxylamine, semicarbozones from semicarbozide are formed but as white precipitate. Uses of methanal, benzaldehyde and acetophenone Uses of methanal (formaldehyde) Formaldehyde is a gas and soluble in water. Its 40% solution in water is called formalin Formaldehyde is used (i) for the manufacture of thermosetting plastics like urea formaldehyde resin and Bakelite. (ii) for the preparation of urotropin which is an urinary antiseptic. (iii) for the manufacture of explosives like RDX (cyclonite), pentaerithrotetranitrate (PETN), etc (iv) for preserving biological specimens. (v) in leather industry for tanning hides (vi) for silvering mirrors. Uses of benzaldehydes Benzaldehyde is used (i) for synthesis of benzoyl chloride, cinnamic acid, cinnamaldehyde, benzoin etc. 112 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids (ii) for the manufacture of dyes like malachite green (iii) in formulating perfumes and flavouring agents due to its characteristic odour. (iv) for preparation of Schiff’s bases which are employed as antioxidants in rubber industry. Uses of acetophenone Acetophenone is used (i) as hypnotic under the trade name hypnone. It is replaced by more effective drugs. (ii) for the preparation of phenacyl chloride which has lachrymatory action (to bring tears in eyes). Hence used in the manufacture of tear gas shells. (iii) in preparation of perfumes due to its pleasant odour. (iv) for the preparation of oximes, N-substituted amides, etc Quick Quiz - 1 1. MPV reduction involves conversion of (A) aldehyde to carboxylic acid (B) ketones to carboxylic acid (C) aldehyde to primary alcohol (D) ketones to secondary alcohol 2. The major product of reduction of propen-1-al using NaBH4 is (A) propenol (B) propanol (C) isopropyl alcohol (D) prop-1-en-2-ol 3. Acetaldehyde and pentan-3-one can be separated using (A) NH3 (B) HCN (C) NaHSO3 (D) none of (A), (B) and (C) 4. Carbonyl compound which does not form precipitate with 2,4-dinitrophenylhydrazine is (A) acetaldehyde (B) benzaldehyde (C) acetone (D) benzophenone 5. Aldehydes cannot be prepared by using (A) Oppenauer oxidation (B) Etard reaction (C) Friedel-Crafts acylation (D) both (A) and (C) 6. Benzaldehyde and benzophenone can be distinguished by using (A) Fehling’s solution (B) Tollen’s reagent (C) Benedict’s solution (D) all of (A), (B) and (C) 7. Acetone reacts with hydrogen cyanide to give (A) acetone cyanohydrin (B) acetoxime (C) 2-hydroxy-2-methyl propanenitrile (D) 3-hydroxy-2-methylpropanenitrile 8. Least boiling point having compound is (A) acetone (B) formaldehyde (C) acetophenone (D) benzophenone 9. The total number of aldehydes and ketones having the molecular formula C 4 H 8O is (A) 2 (B) 3 (C) 4 (D) 5 10. The black colour precipitate which gives mirror like appearance to the walls of test tube when acetaldehyde is heated with Tollen’s reagent is (A) CH3COOH (B) Ag (C) NH3 (D) CH3COOAg 113 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Illustrations - 1 1. The IUPAC name of dibenzyl ketone is (A) benzophenone (B) 1, 3-diphenylproan-2-one (C) 1, 2-diphenylpropan-2-one (D) 1, 2-diphenylpropan-1-one Ans (B) O 3 2 1 C6 H5CH2 C CH2 C6 H5 ; 1, 3-diphenylpropan-2-one 2. Carbon atom of carbonyl group acts as (A) electrophilic center (B) nucleophilic center (C) Lewis base (D) both (A) and (C) Ans (A) + − C O electrophilic center 3. When a mixture calcium formate and calcium acetate is subjected to dry distillation the product which is not formed is (A) formaldehyde (B) acetaldehyde (C) acetone (D) butanaldehyde Ans (D)  2 Calcium formate formaldehye  2 Calcium acetate acetone Calcium formate + Calcium acetate acetaldehye O3/CH2Cl2 Zn/H2O 4. Given A B HCHO + CH3CHO, A is  (A) propyne (B) but-1-ene (C) propene (D) but-2-ene Ans (C) (i) O3/CH2Cl2 CH3CH CH2 CH3CHO + HCHO  A (ii) Zn/H2O 5. Acetyl chloride reacts with (CH3)2Cd to give (A) acetone (B) propanone (C) acetaldehyde (D) propanaldehyde Ans (A) (CH3)2Cd + 2CH3COCl 2CH3COCH3 + CdCl2 6. Carbonyl compound which more reactive towards nucleophilic addition reactions is p-methexybenzaldehyde (A) formaldehyde (B) propanal (C) acetone (D) benzaldehyde Ans (A) Reactivity of carbonyl compounds decreases with increase in number of +I groups and stearic hindrance. 114 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids 7. Acetaldehyde reacts with hydroxylamine to give (A) ethanaloxime (B) acetoxime (C) acetaldoxime (D) both (A) and (C) Ans (D) H H CH3 C O + H2N OH CH3 C N OH + H2O ethanaloxime (acetaldoxime) H2/Ni 8. Given A CH3 CH CH2OH, A is CH3 (A) butanone (B) 2-methylbutanal (C) 2-methylpropanal (D) 2-methylpropanone Ans (C) [O] CH3 CH CHO CH3 CH CH2OH CH3 CH3 9. The number of aldehydes including stereoisomers with the molecular formula C5H10O is (A) 5 (B) 4 (C) 3 (D) 2 Ans (A) Aldehydes representing structural isomers with molecular formula C5H10O are given below. O O H H H H O H O Number of structural isomers = 4 Number of aldehydes including stereoisomers = (4 + 1) = 5. Think Further (i) Predict the number of possible alkanones with molecular formula C5H10O. (ii) How many cycloalkanones are possible (excluding stereoisomers) with molecular formula C5H8O? (iii) Predict the number of optically active cycloalkanols with molecular formula C4H8O 10. The compound (X) C3H6O when heated with alkali gives 2-methylpent-2-enal. The compound (X) is (A) propanal (B) propanone (C) prop-2-en-1-ol (D) cylclopropanol Ans (A) The compound (X) is propanal and undergoes aldol reaction.. HO(aq) H H heat O O (X) 115 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Think Further (i) How many aldol products (excluding stereoisomers) are formed when compound (X) and ethanal mixture is treated with alkali? (ii) Name the product formed when benzaldehyde and compound (X) are treated with alkali. (iii) Name the isomer of (X) which responds to iodoform reaction. Carboxylic acids The organic compounds containing one or more carboxyl group/s (−COOH) in a molecule are called carboxylic acids. Nomenclature The carboxylic acids are classified as mono, di, tri, etc., carboxylic acids depending upon the number of −COOH group/s present in a molecule. Most of the carboxylic acids are better known by common name (trivial name). The common name and IUPAC names of a few carboxylic acids are given below. Structure Common name IUPAC name HCOOH formic acid methanoic acid CH3COOH acetic acid ethanoic acid CH3(CH2)3COOH valeric acid pentanoic acid CH3(CH2)4COOH caproic acid hexanoic acid CH3(CH2)16COOH stearic acid octadecanoic acid Many carboxylic acids and their derivatives are naturally occurring. The vinegar used in salad is 5% acetic acid solution. Formic acid is the substance in the sting of a bee that irritates the skin. The -hydroxy carboxylic acids are widely distributed in nature and found in fruits, milk, sugarcane, etc. Dermatologists have been using products with high concentration of -hydroxycarboxylic acids to remove acne scars and reduce irregular pigmentation, age spots, etc. Glycolic, lactic, malic, tartaric and citric acids are most frequently used at concentrations (8−10%) in skin care products to soften cells and lessen wrinkles. OH OH O OH HO OH HO O OH O O OH glycolic acids lactic acid tartaric acid (sugar cane, beet) (sour milk) (tamarind, grape) O O HO O HO OH HO OH O OH HO O malic acid citric acid (apple, grape) (citrus fruits-lemon, orange) 116 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids Dicarboxylic acids contain two −COOH groups in a molecule. They may be aliphalic or aromatic. Some common dibasic acids with common and IUPAC names are given Structure Common name IUPAC name COOH oxalic acid ethanedioic acid COOH COOH malonic acid propanedioic acid H2C COOH succinic acid butanedioic acid CH2 COOH CH2 COOH CH2 COOH glutaric acid Pentanedioic acid H2C CH2 COOH adipic acid hexanedioic acid CH2CH2COOH CH2CH2COOH H COOH maleic acid cis-2-butenedioc acid C C H COOH COOH phthalic acid 1,2-benzenedicarboxylic acid COOH Isomerism The alkanoic acids exhibit chain and functional isomerism in addition to optical isomerism. Alkanoic acids are functional isomers of alkylalkanoates (esters), alkenediols, cycloalkanediols, hydroxyl alkoxyalkenes, hydroxycyclicethers, etc. General methods of preparation 1. From alkenes and alkynes When alkenes or alkynes are subjected to oxidative cleavage (O3/H2O2) or an oxidation with alkaline potassium permanganate followed by acidificative gives carboxylic acids. O O (i) O3 RCH CH R' R C OH + R' C OH (ii) H2O2.. (i) MnO4 /HO (aq) OH HO (ii) H3O+ O O.... O O MnO4 /HO (aq) RC CR' R C OH + R C OH H3O+ 117 ACTIVE SITE EDUTECH- 9844532971  ACTIVE SITE Aldehydes, Ketones & EDUTECH Carboxylic Acids 2. From haloalkanes: Following reactions are employed for the conversion of haloalkanes into carboxylic acids. Mg/ether RCH2MgX O