Carboxylic Acids Acid Derivatives

CARBOXYLIC ACIDS & ACID DERIVATIVES

Introduction :

Compounds containing the carboxyl group are distinctly acidic and are called carboxylic acids. O

R – C – O – H Carboxylic acid

There have general formula C_nH_2nO₂

Carboxylic acid derivatives are compounds with functional groups that can be converted to carboxylic acids by a simple acidic or basic hydrolysis. The most important acid derivatives are esters, amides, nitriles, acid halides and anhydrides.

O R – C – X acid halide O O R – C – O – C – R anhydride O R – C – O – R' ester RCO R' O R – C – NH2 amide RCONH R – C N nitrile

Esters and amides are particularly common in nature. For example, isoamyl acetate found in ripe bananas and geranyl acetate is found in the oil of roses, geraniums and many other flowers. N, N-diethyl-meta-toluamide (DEET) is one of the best insect repellents known and penicillin G is one of the antibiotics that revolutionized modern medicine.

O O – C – CH3 isoamyl acetate (banana oil) O O – C – CH3 geranyl acetate (geranium oil) C O N(CH CH )2 3 2 N, N-diethyl-meta-toluamide H C3 H C3 H C3 H C3 H C3 H C3 H C3 H C3 H C3 H C3 H C3 O O PhCH – C – NH2 N S COOH CH3 CH3 Penicillin G

IUPAC Nomenclature of Acid and Acid derivatives:-Table- 1 O O O O O O O O O O O O O O O O O

Compound IUPAC Name

(1) H – C – OH (2) CH – C – OH3 (3) CH – CH – C – OH3 Ethanoic acid Methanoic acid 2-Cyclohexylpropanoic acid 3-Oxo-2-propylbutanoic acid (4) CH CCH – C – OH3 CH CH CH2 2 3 (5) CH – CH – CH – C – OH2 2 2 (6) CH CH CH –3 2 CH2– C – OH NH2 4-Aminobutanoic acid Ph (7) CH – CH – CH – C – OH3 2 (8) CH – C – F3 (9) CH –3 CH –2 C – Cl (10) CH – CH –3 CH –2 C – Br CH3 3-Phenylpentanoic acid 3-Methylbutanoic acid Ethanoylfluoride Propanoylchloride Br 3-Bromobutanoylbromide (11) – C – Cl Cyclopentanecarbonyl_chloride (12) CH – C – O – C – CH3 3 (13) CF – C – O – C – CF3 3 Ethanoic anhydride Trifluoroethanoic anhydride (14) O O 1,2-Benzenedicarboxylic anhydride

O O O O O O O CH – C – O – C – H3 CH3CH2– C – O – C – CF3 Trifluoroethanoic propanoic anhydride Ethanoic methanoic anhydride Cyclopropane carbonitrile 3-Cyanopentanoic acid C – OCH CH2 3 CN Ethyl o-cyanobenzoate –C N CH – CH – CH – CH – COOH3 2 2 – CN C – NH2 C – H 2-Formylcyclohexane carboxamide CH – CH – CH – C N3 2 OH 2-Hydroxybutane nitrile

Dicarboxylic acids

If the substituent is a second carboxyl group, we have a dicarboxylic acid. For example :

acid opanedioic Pr acid Malonic COOH HOOCCH₂ acid edioic tan Bu acid Succinic COOH CH HOOCCH_{2 2} acid c Hexanedioi acid Adipic COOH CH CH CH HOOCCH_{2 2 2 2} CHCOOH CH HOOCCH_{2 2} 2 2 3 COOH CCH HOOCCH | CH CHCOOH HOOCCHCH₂

Physical properties of acids and acid derivatives :

(1) First three members are colourless pungent smelling liquid. The next three members also colurless oily liquid with unpleasant smell. Higher member (> 7) are colourless waxy solids.

(2) Boiling points:

The boiling point of carboxylic acids are higher than that of alcohols, ketones or aldehydes of similar molecular weight. CH – C – OH acetic acid, bp 118ºC 3 O CH OH 1-propanol bp 97ºC 3CH CH2 2 CH bp 49ºC 3CH CH Propionaldehyde 3 O

The high boiling points of carboxylic acids is the result of formation of a stable hydrogen-bonded dimer.

R – C _{C – R}

O --- H – O

O – H --- O hydrogen bonded acid dimer

Carboxylic acids have higher boiling points than corresponding molucular mass alcohols because of -(i) –OH bond in carboxylic acid is more polar than alcohol due to the presence of group. (ii) Carboxylic acid molecules are held together by two H-bonds.

Esters and acid chlorides have boiling points near those of the unbranched alkanes with similar molecular weights.

Nitriles also have higher boiling points than esters and acid chlorides of similar molecular weight. This effect results from a strong dipolar association between adjacent cyano groups.

R – Cδ+ N :δ–  δ – δ +

: N C – R (dipolar association of nitriles)

These acid derivatives contain highly polar carbonyl groups, but the polarity of the carbonyl group has only a small effect on the boiling points.

× × × × × × × × × × acid chlorides × × × × × × × × × × × × × × × × × × × × × × × × N,N-dimethyl 3° amides methyl esters 1° aocohol acids n-alkanes 200 300 100 0 –100 B o ili n g p o in t (º C ) nitriles 1° amides N-methyl 2°amides CH –C–NH3 2 O CH –C–OH3 O CH CH CH OH3 2 2 O CH CH –C N3 2  CH CH CH CH3 2 2 3 Examples (MW 55 – 60) bp(ºC) 222 118 97 97 H–C–OCH3 32 0

(3) Melting points :

Acids containing more than 8 carbon atoms are generally solids, unless they contain double bonds. The presence of double bonds (especially cis double bond) in a long chain impedes the formation of a stable crystal lattice resulting in a lower boiling point.

O CH – (CH ) – C – OH3 2 16 Stearic acid, mp 70ºC O C = C C = C H _{H H H} CH (CH )3 2 4 CH2 (CH ) – C – OH2 7 linoleic acid mp –5ºC

Melting point of carboxylic acids : There is no regular pattern in melting point of carboxylic acid (up to 10 carbon atoms) having even number of C atoms are higher than neighbouring members having odd number of C atoms because carboxylic acid and methyl group in even members lie in opposite side of zig-zag carbon chain hence they fit better into crystal lattice resulting in higher melting points.Vice-versa is observed in case of carboxylic acid having odd no. of carbon atoms.

Amides have surprisingly high boiling points and melting points compared with other compounds of similar molecular weight. Primary and secondary amides participate in strong hydrogen bonding.

C R _N R' R' :O: . . C R _N R' R' :O: + . . – C = N C = N O R R H H H H + + – – – ... O . . .O C R N – H + H Hydrogen bonding – R' N R' C R O + + – _– + O C R N R' R' + Intermolecular attraction

Strong hydrogen bonding between molecules of primary and secondary amides also results in unusually high melting points.

O H – C – N CH3 CH3 dimethylformamide (DMF) mp –61ºC O CH – C – N3 H CH3 N-methylacetamide m.p. 28ºC O CH3CH2CN H H Propionamide mp 79ºC (4) Solubility:

Carboxylic acids form hydrogen bonds with water and the lower molecular - weight carboxylic acids ( u p t o 4 carbon atoms) are miscible with water.

Physical Properties of Carboxylic Acids

Table -2

IUPAC name Common Name Formula mp bp Solubility

(ºC) (ºC) (g/100 g H₂O)

Methanoic formic HCOOH 8 101  (miscible)

Ethanoic acetic CH₃COOH 17 118 

Propanoic propionic CH₃CH₂COOH –21 141 

2-Propenoic acrylic H₂C=CH–COOH 14 141 

Butanoic butyric CH₃(CH₂)₂COOH –6 163 

2-Methylpropanoic isobutyric (CH₃)₂CHCOOH –46 155 23 Trans-2-butenoic crotonic CH₃–CH=CH–COOH 71 185 8.6

Pentanoic valeric CH₃(CH₂)₃COOH –34 186 3.7

3-Methylbutanoic isovaleric (CH₃)₂CHCH₂COOH –29 177 5 2,2-Dimethylpropanoic pivalic (CH₃)₂C–COOH 35 164 2.5

Hexanoic caproic CH₃(CH₂)₄COOH –4 206 1.0

Octanoic caprylic CH₃(CH₂)₆COOH 16 240 0.7

Decanoic capric CH₃(CH₂)₈COOH 31 269 0.2

Physical Properties of Acid Derivatives

Table -3

Compound Name mp (ºC) bp (ºC) Water

Solubility

CH₃COCl Ethanoylchloride (CH₃CO)₂O Ethanoic anhydride

CH₃COOH Ethanoic acid 17 118 

CH₃CONH₂ Ethanamide 222 CH –C–OCH CH3 2 3 O Ethyl acetate – 83 77 10% H–C–N(CH )3 2 O Dimethylformamide (DMF) – 61 153 miscible CH –C–N(CH )3 3 2 O

Dimethylacetamide (DMA) – 20 165 miscible

CH₃–C N Acetonitrile – 45 82 miscible

Methods of preparation of carboxylic acids

1. Synthesis of carboxylic acids by the carboxylation of grignard reagents

RMgX + O = C = O ether Dry_    R C OMgX || O   H /H2O    _{R C}|| _OH O  

e tan Chlorobu 2 Cl | CH CHCH CH_{3 2 3}  1. Mg / diethyl ether 2. CO2 3. H O3 + %) 86 76 ( acid oic tan Methylbu 2 H CO | CH CHCH CH 2 3 2 3   1. Mg / diethyl ether 2. CO2 3. H O3 + Ex. 3 3 CH | MgBr CH CH   _ H / O H ) ii ( CO ) i ( 2 2 ) acid propanoic methyl 2 ( acid Isobutyric CH | COOH CH CH 3 3   

2. Synthesis of Carboxylic acids by the hydrolysis of nitriles Mechanism :

+ + H+  heat ₊

Hydrolysis of cyanides (Acid catalysed) :

Ex. _DMSONaCN CH CN2

Benzyl cyanide (92%) CH COH2 Phenylacetic acid (77%) || O Ex. CH CCH CH CH3 2 2 3 | OH | CN

Note: (1) Alkyl cyanides needed for the purpose can easily be prepared from the corresponding alkyl halides with alcoholic KCN or NaCN.

R – Cl + KCN R – C  N + KCl

(2) This reaction is used to ascend the series having one carbon atom more than the corresponding alkyl halides which are prepared from alcohol on treating with phosphorus halide.

ROH + PX₅ R – X + POX₃+ HX

(3) This hydrolysis of alkyl cyanide provides a useful method to get carboxylic acid having one carbon atom more than the original alkyl halide and alcohols.

3. By oxidation of alkylbenzenes - aromatic acids are produced.

O H / H ) ii ( ¯ OH / KMnO 2 4      O H / H ) ii ( ¯ OH / KMnO ) i ( 2 4       Ex. 4 2 7 2 2 SO H O Cr K      

Chemical Reactions

Acidity of carboxylic acids:-R – C – OH O -R – C – O O (I) + _H (i)R – C – O -O

(I) exists as two equivalent canonical structures I(A) and I(B). This ion is resonance stablised

and resonance hybrid structure is I(C). -R – C O O I(A) -R – C O O I(B) R – C O O I(C) (ii) R – C – O -O

ion is more stable due to resonance, hence carboxylic acids are acidic in nature.

(iii) Electron withdrawing group (–I effect) stablises the anion and hence, increases acidic nature.

C O O X

Ex. F – CH₂– COOH > Cl – CH₂COOH > Br – CH₂COOH > I – CH₂COOH

Ex. Cl – C – COOH Cl Cl >Cl – CH – COOH Cl > Cl – CH₂COOH > CH₃COOH

(iv) Electron releasing group (+ I effect) destablises the anion and hence decreases acidic nature.

C O O X

Ex. HCOOH > CH₃COOH > CH₃– CH₂– COOH

Ex. COOH COOH > COOH COOH CH2 > CH2– COOH CH2– COOH

Ex. Relative acid strength

is:-RCOOH > HOH > ROH > HC  CH > NH₃> RH

Note Acidity of acids is compared by compairing stability of conjugate base. 2. Reaction involving removal of proton from –OH group.

(i) Action with blue litmus : All carboxylic acids turn blue litmus red. (ii) Reaction with metals :

2 CH₃COOH + 2Na + H₂

2CH₃COOH + Zn + H₂ (iii) Reaction with alkalies :

CH₃COOH + NaOHCH₃COONa + H₂O (iv) Reaction with carbonates and bicarbonates :

2CH₃COOH + Na₂CO₃2CH₃COONa + CO₂+ H₂O CH₃COOH + NaHCO₃CH₃COONa + CO₂+ H₂O

Reaction of carboxylic acid with aqueous sodium carbonate solution produces brisk efferuescence. However most phenols do not produce effervescence. Therefore, the reaction may be used to distinguish between carboxylic acids and phenols.

(v) Reaction with grignard reagent :

R–CH₂MgBr + RCOOH R–CH₃+ RCOOMgBr

Note: A stronger acid displaces a weaker acid from the salt of the weaker acid.

Ex. CH₃COOH (Stronger acid) + CH₃ONa CH₃COONa + CH₃–OH (Weaker Acid)

Ex. CH₃COOH (stronger acid) + NaHCO₃CH₃COONa + H₂CO₃(Weaker acid)H₂O + CO₂ (lab. test of carboxylic acid)

3. Reaction involving replacement of –OH group

Ex. + SOCl₂ + SO₂ + HCl

Ex. + PCl₅ + POCl₃+ HCl

(ii) Fisher Esterification

Carboxylic acid react with alcohol to form esters through a condensation reaction known as esterification. General Reaction :

+ R – OH + H₂O

Specific Examples:

+ CH₃CH₂–OH

+ CH₃–OH

Mechanism : (Acid catalysed esterification)

If we follow the forward reactions in this mechanism, we have the mechanism for the acid catalysed esterification of an acid. If however, we follow the reverse reactions, we have the mechanism for the acid catalysed hydrolysis of an ester. Acid catalysed ester hydrolysis.

which resut we obtain will depend on the condition we choose. If we want to esterify an acid, we use an excess of the alcohol and, if possible remove the water as it is formed. If we want to hydrolyse an ester, we use a large excess of water that is we reflux the ester with dilute aqueous HCl or dilute aqueous H₂SO₄.

(iii) Formation of amides :

In fact amides can not be prepared from carboxylic acids and amines unless the ammonium salt is heated strongly to dehydrate it. This is not usually a good method of preparing amides.

(iv) Formation of acid anhydride :

4. Decarboxylation reactions : (i) Soda-lime decarboxylation :

General reaction :

In this reaction carbanion intermediate is formed.

Rate of reaction depends upon the stability of carbanion intermediate.

Electron with drawing group at R–COOH will increases the rate of decarboxylation.

Ex.

Rate of decarboxylation. I > II > III > IV

(ii) (a) Decarboxylation of-keto carboxylic acids:

Acids whose molecules have a carbonyl group one carbon removed from the carboxylic acid group, called -keto acids, decarboxylate readily when they are heated to 100–150ºC.

There are two reasons for ease of decarboxylation.

When the acid estelf decarboxylates, it can do so through a six membered cyclic trensition state :

This reaction produces an enol directly and avoids an anionic intermediate. The enol then tautomerises to a methyl ketone.

When the carboxylate anion decarboxylates, it forms a resonance stabilized enolate anion.

Alphatic acids that do undergo successful decarboxylation have certain functional groups or double or triple bonds in the or  positions.

(iii) Kolbe’s electrolysis

2RCOOK + 2HOH Electrolysis R – R + 2CO₂+ H₂+ 2KOH Mechanism : R CO₂K R CO₂–_{+ K}+ At Anode : R CO₂–  _R  2 CO + e– _(oxidation) (I) R CO₂  R + CO₂ (II)  R + R  R – R

If n is the number of carbon atoms in the salt of carboxylic acid, the alkane formed has 2(n–1) carbon atoms. Ex. 2CH₃– COOK + 2H₂O Electrolysis CH₃CH₃+ 2CO₂+ H₂+ 2KOH.

(iv)

Hunsdiecker Reaction (Bromo-decarboxylation) :

Mechanism :

Step 1 : R.COOAg + X₂ + AgX

Step 2 :

Step 3 : Step 4 :

Although bromine is the most often used halogen, chlorine and iodine have also been used.

When iodine is the reagent, the ratio between the reactant is very important and determines the product A 1 : 1 ratio of salt to iodine gives alkyl halide, as above. A 2 : 1 ratio, however gives the ester RCOOR. This is called simonini reaction and sometimes used to prepare carboxylic ester.

5.

HVZ Reaction (Halogenation of aliphatic acids and Substituted acids)

In the presence of a small amount of phosphorus, aliphatic carboxylic acids react smoothly with chlorine or bromine to yield a compound in which-hydrogen has been replaced by halogen. This is the Hell-Volhard-Zelinsky reaction. Because of its regioselectivity-only alpha halogenation-and the readiness with which it takes place, it is of considerable importance in synthesis.

CH₃COOH Cl2,P ClCH₂COOH Cl2,PCl₂CHCOOH Cl2,P Cl₃CCOOH

The halogen of these halogenated acids ungergoes nucleophilic displacement and elimination much as it does in the simpler alkyl halides. Halogenation is therefore the first step in the conversion of a carboxylic acid into many important substituted carboxylic acids.

acid enated log ha An Br | RCHCOOH   + large excess of NH₃  acid o min a An NH | RCHCOOH 2   Br | NaOH RCHCOOH  OH | RCHCOONa _{ }H_ acid hydroxy An OH | RCHCOOH   Br | ) alc ( KOH CHCOOH RCH₂   RCH = CHCOO¯    H acid d unsaturate , An CHCOOH RCH    

Summary of reactions of carboxylic acids :

Carboxylic Acid Derivatives

Closely related to the carboxylic acids and to each other are a number of chemical families known as functional derivatives of carboxylic acids : acid chlorides, anhydrides, amides, and esters, These derivatives are compounds in which the —OH of a carboxyl group has been replaced by —CI,—OOCR, — NH₂, or —OR`.

Acid chloride Anhydride Amide Ester

They all contain the acyl group,

Like the acid to which it is related, an acid derivative may be aliphatic or aromatic, substituted or unsubstituted; whatever the structure of the rest of the molecule, the properties of the functional group remain essentilly the same.

Characteristic reaction of acid deerivatives (Nucleophilic acyl substitution) :

Nucleophilic acyl substitution usually takes place by an addition-elimination mechanism.The incoming nucleophile adds to the carbonyl to form a tetrasubstituted intermediate with a tetrahedral carbon.

  

The tetrahedral intermediate formed when a nucleophile attacks the carbonyl carbon of a carboxylic acid derivative is not stable and cannot be isolated.

A pair of nonbonding electrons on the oxygen reforms the p bond, and either or is eliminated with its bonding electrons. Whether or is eliminated depends on their relative basicities. The weaker base is preferentially eliminated because the weaker the base, the better it is a leaving group.

Thus carboxylic acid derivative will undergo a nucleophilic acyl substitution reaction provided that the incoming nucleophile is a stronger base than the group that is to be replaced. If the incoming nucleophile and the group attached to acyl group in the starting material have similar basicities, the tetrahedral intermediate can expect either group with similar ease. A mixture of starting material and substitution product will result.

(i) 

(iii) 

(iv) 

(v) 

Condition for acyl nucleophilic substitution reaction :

(i) L must be better leaving group than , i.e., basicity of Nu should be more than that of (ii) must be a strong enough nucleophilic to attack RCOL.

(iii) Carbonyl carbon must be enough electrophilic to react with .

(A) Acid halides

Methods of preparation of Acyl halides

(i) RCOOH + PCl₅  RCOCl + POCl₃+ HCl (ii) 3RCOOH + PCl₃ 3RCOCl + H₃PO₃

(iii) RCOOH + SOCl₂ Pyridine RCOCl + SO₂+ HCl

Ex. 3CH₃COONa + PCl_{3  }Distil_

chloride Acetyl 3 3 3COCl Na PO CH 3  Ex. benzoate . Sod 3 5 6H COONa POCl C 2  _{ }Distil_ chloride Benzoyl NaPO NaCl COCl H C 2 _{6 5}   ₃

Chemical Reactions

(1) Reaction with carboxylic acids

Acyl chlorides react with carboxylic acids to yield acid anhydrides. When this reaction is used for preparative purposes, a weak organic base such as pyridine is normally added. Pyridine is a catalyst for the reaction and also acts as a base to neutralize the hydrogen chloride that is formed.

+ + CH (CH ) CCl3 2 5 Heptanoyl chloride O +

(2) Reaction with alcohols

Acyl chlorides react with alcohols to form esters. The reaction is typically carried out in the presence of pyridine.

+ +

+

(3) Reaction with ammonia and amines

+ + + +

(4) Hydrolysis

Acyl chlorides react with water to yield carboxylic acids. In base, the acid is converted to its carboxylate salt. The reaction has little preparative value because the acyl chloride is nearly always prepared from the carboxylic acid rather than vice versa.

+ water O H₂ + + water O H₂ +

(5) Reaction of acid halide with organometallic (a) with Grignard reagent

(6) Reduetion of acid halides (a) Reduction by LiAIH₄

(b) Reduction with H₂/Pd / BaSO₄(Rosenmund reduction)

Summary of reactions of acid halide

(B) Acid amides

Methods of preparation of acids amides

1. By reaction of esters with ammonia and amines

Ex. + +

Ammonia is more nucleophilic than water, making it possible to carry out this reaction using aqueous ammonia. Ex. Methyl 2-methylpropenoate H C = C – COCH2 3 | || CH3 O + 2-Methylpropenamide (75%) H C = C – CNH2 2 | || CH3 O +

Amines, which are substituted derivatives of ammonia, react similarly :

Ex. + +

Ex. + +

Ex. + +

2. From acid halides

RCOCl + 2NH₃  RCONH₂+ NH₄Cl 3. From anhydride

(RCO)₂O + 2NH_{3 } RCONH₂+ RCOONH₄ 4. From esters

RCOOR + NH_{3 } RCONH₂+ ROH

5. From ammonium salt of carboxylic acid

RCOONH_{4 } RCONH₂+ H₂O acetate . Amm 4 3COONH CH  Acetamide 2 3CONH CH 6. From cyanides R – C N + H₂O NaOH O H or HCl . Conc 2 2        R – CONH₂ O H N C CH₃   ₂ Conc.H2SO4 2 3 CONH CH  7. +

Chemical Reactions

1.

Hoffmann rearrangement

In the Hofmann rearrangement an unsubstituted amide is treated with sodium hydroxide and bromine to give a primary amine that has one carbon fewer than starting amide

General reaction.

Mech :    OH CO₂R–NH R – NH₂ (2) Hydrolysis of amides + +

In acid, however, the amine is protonated, giving an ammonium ion, R₂ :

+ +

In base the carboxylic acid is deprotonated, giving a carboxylate ion :

+ +

The acid-base reactions that occur after the amide bond is broken make the overall hydrolysis irreversible. In both cases the amine product is protonated in acid ; the carboxylic acid is deprotonated in base.

Ex.     H2O/H2SO4 + Ex. +

Summary of reaction of amide: Ex. Ans. O || NH C CH CH₃ ₂  ₂

(C) Esters

Methods of Preparation

(ii) CH₃COCl + C₂H₅OH Pyridine CH₃COOC₂H₅+ HCl

Alcohols react with acyl chlorides by nucleophilic acyl substitution to yield esters. These reactions are typically performed in the presence of a weak base such as pyridine.

+ + +

Chemical Reactions

1. Acid catalysed hydrolysis of ester (A_Ac2):

Because H₂O and R—OH have approximately the same basicity, it will be eqully easy for tetrahedral imtermediate I to collapse to reform the ester as it will be for tetrahedral intermediate II to collapse to form the carboxylic acid. Consequently, when the reaction has reached equilibrium, both ester and carboxylic acid will be obtained.

CH₃COOH + ROH Excess water will force the equilibrium to the right.

CH₃COOH + ROH

Mechanism:

2. Base-Promoted Hydrolysis of Esters : Saponification (B_Ac2):

Esters not only undergo acid hydrolysis, they also undergo base-promoted hydrolysis. Base-promoted hydrolysis is sometimes called saponification, from the Latin word sapo, soap. Refluxing an ester with aqueous sodium hydroxide, for example, produces an alcohol and the sodium salt of the acid :

The carboxylate ion is very unreactive toward nucleophilic substitution because it is negatively charged. Base-promoted hydrolysis of an ester, as a result, is an essentially irreversible reaction.

The mechanism for base-promoted hydrolysis of an ester also involves a nucleophilic addition-elimination at the acyl carbon.

Evidence for this mechanism comes from studies done with isotopically labeled esters. When ethyl propanoate labled with18_{O in the ether-type oxygen of the ester(below) is subjected to hydrolysis with aqueous NaOH} all of the18_{O shows up in the ethanol that is produced. None of the}18_{O appears in the propanoate ion.}

This labeling result is completely consistent with the mechanism given above . If the hydroxyide ion had attacked the alkyl carbon instead of the acyl carbon, the alcohol obtained would not have been labled. Attack at the alkyl carbon is almost never observed.

Although nucleophilic attack at the alkyl carbon seldom occurs with esters of carboxylic acids, it is the preferred mode of attack with esters of sulfonic acids (e.g. tosylates and mesylates)

Summary of reaction of esters :

(D) Acid anhydrides

Methods of Preparation of acid anhydrides

HOOCCH COOH CH₃  ₃ P2O5, _{CH CO.O.CO.CH H O} 2 3 3 

Ex. P2O5,

Ex. P2O5,

Ex. P2O5, ₊

Ex. P2O5,

five or six membered cyclic anhydride are stable 2. From acid and acid halide

CH₃COOH + CH₃COCl PyridineCH₃CO.O.COCH₃+ HCl Ex. CH₃COCl + CH₃COONa  CH₃CO.O.COCH₃+ NaCl

Chemical Reactions

(1) Reaction with aromatic compounds (Friedel crafts acylation)

+ ArH +

Ex. + +

(2) Reaction with alcohols

Acid anhydrides react with alcohols to form esters. The reaction may be carried out in the presence of pyridine or it may be catalysed by acids. In the example shown, only one acyl group of acetic anhydride

+ +

Ex. + + CH₃COOH

(3) Reaction with ammonia and amines

Acid anhydrides react with ammonia and amines to form amides. Two molar equivalents of amine are required. In the example shown, only one acyl group of acetic anhydride becomes incorporated into the amide and the other becomes the acyl group of the amine salt of acetic acid.

+ +

+ + CH₃COOH

(4) Hydrolysis

Acid anhydrides react with water to yield two carboxylic acid functions. Cyclic anhydrides yield dicarboxylic acids.

+ +

+

7.

Heating Effects :

(b) Heating effect on dicarboxylic acid

CH₃– COOH

(c) Heating effects on Hydroxy acids

(1) – Hydroxy acid

(2) – Hydroxy acid

(3) – Hydroxy acid

Since 4 or 8 membered rings are less stable the refore-Hydroxy acids on heating produce  unsaturated carboxylic acid.

(4) – Hydroxy acid

(d) Heating effects on esters

R` – COOH to R` – CH = CH₂

Mech : R` – CH = CH₂+ R – COOH

MISCELLANEOUS SOLVED PROBLEMS (MSPS)

(A) (I) decarboxylates faster than (II) on heating. (B) Only *CO₂is eliminated on heating of compound (I).

(C) Compound (I) eliminates a mixture of CO₂and *CO₂on heating. (D) The rate of decarboxylation of (II) is faster than (III).

Ans. (A) Sol.

No decarboxylation CO₂ CO₂rate of decarboxylation :III > I > II

2. final product is : (A) (B) (C) (D) Ans. (B) Sol. 3. final product is (A) (B) (C) (D) Ans. (B) Sol.

4. Identify (A), (B), (C) and (D). C₃H₅Cl (A) Mg/dryether (B) _ H / O H ) ii ( CO ) i ( 2 2 _(C)  [O] _C 8H12(D) Saturated Ans. (A) = ; (B) = ; (C) = ; (D) =

5. Preparation of propanoic acid from ethyl alcohol follows : Sol. CH₃– CH₂OH _{ }PCl_5 CH 3– CH2– Cl  KCN CH3– CH2– CN   H / O H2 CH 3– CH2– COOH

6. Identify (A), (B) and (C).

C₃H₆Cl₂(A)  KCN (B) H2O/OH(C) 2 CO     2-Methylpropanoic acid Sol. Cl | CH – C – CH | Cl 3 3  KCN CN | CH – C – CH | CN 3 3   OH / O H2 COOH | CH – C – CH | COOH 3 3 2 CO     2-Methylpropanoic acid

7. Find the rate of soda-lime decarboxylation.

Sol. Rate of soda-lime decarboxylation. I > II > III > IV > V 8. Identify (A), (B) and (C).

CH₃– CH₂– COOH _Br2_(1eqV_)/_P_ (A)  KCN (B) H2O/H/(C)

Sol. (A) Br | COOH — CH — CH_{3 ; (B)} CN| COOH — CH — CH₃ ; (C) CH₃—CH₂—COOH

9. Write the structures of (A) C₃H₇NO which on acid hydrolysis gives acid (B) and amine (C). Acid (B) gives (+)ve silver–mirror test.

Ans. A = or

10. Predict A , B , C , D and E.

Acid (A)  B Mesitylene/AlCl3

Sol. (A) = CH₃COOH; (B) =

O O || || CH — C — O — C — CH_{3 3}; (C) = (D) =

11. Which of these represents correct reaction ? (A) conc.NaOD DCOO–_{+ DCH}

2OD (B) +  NaOH _C(CH 2OH)4+ HCOO – (excess) (C) PBr2 (D) + O H SO H . conc 2 4 2       Ans. (A,B,C,D)

Sol. (A) _conc_.NaOD_{ DCOO}–_{+ DCH}

2OD (Cannizzaro reaction)

(B) + _{ }NaOH_{ C(CH}

2OH)4+ HCOO

– _{(Aldol + Cannizzaro reaction)} (excess) (C) PBr2 _{(HVZ reaction)} (D) + O H SO H . conc 2 4 2       (Esterification reaction)

12. Which are correct against property metioned ?

(A) CH₃COCl > (CH₃CO)₂O > CH₃COOEt > CH₃CONH₂ (Rate of hydrolysis)

(B) CH₃–CH₂–COOH > > (Rate of esterification)

(C) > > (Rate of esterification)

(D) > > Ph–CH₂–COOH (Rate of decarboxylation) Ans. (A,B)

13. Match the product of column II with the reaction of column I.

Column I Column II

(A) _ (p) ester with O18

(B) _ (q) A-diketone with –18_{OH group}