Carboxylic Acid Derivatives

DERIVATIVES OF CARBOXYLIC ACID The –OH of an acid can be replaced by –Cl, –OR, or –NH2 group to yield an acid chloride an ester or an amide. These compounds are called functional derivatives of acid and they all contain acyl group. The functional derivatives are all readily converted into the acid by simple hydrolysis. O R C Acid O R C R O OH –OH +Z R C Z Acid derivative is Acyl group and Z is nucleophile Cl1 , CH 3 COO 1 , C 2 H 5 O 1 , NH 12 etc. –OH +X R O –OH +NH2 R OH –OH R + OR –OH –RCOO O Acyl halide X O Amide NH2 O Ester OR O R O R Anhydride O CHARACTERISTIC REACTION FOR ACID DERIVATIVES IS NUCLEOPHILIC SUBSTITUTION REACTION MECHANISM .. O: .. O CH3 .. C + Nu Z CH3 C O Nu CH3 C Nu + Z Z sp2 hybrid C - atom sp3 hybrid C - atom In this reaction Z is leaving group. Weak bases are good leaving groups. Reactivity order - depends on the basic Character of Z basicity : Cl– < CH 3 COO – < C 2 H 5 O – < NH 2– In the given groups – Cl is the weakest base so it is best leaving group. Reactivity order : CH 3 COCl > CH 3 COOCOCH 3 > CH 2 COOC 2 H 5 > CH 3 CONH 2 CARBOXYLIC ACID & THEIR DERIVATIVES – – In acid derivatives the carbonyl group > C=O is attached to highly electronegative Cl , CH3COO , NH2– etc. group due to electron withdrawing effect of these groups, the electron density on the carbonyl carbon is reduced further. gg Thus acetyl group is readily attacked by Nu shows nucleophilic substitution reaction. Basicity of leaving groups : Weaker the basic character of the leaving group more will be the ease with which the leaving group leaves the compound and hence more is the reactivity Cl– ion being weakest base are most reactive leaving group. The order of basicity of the leaving group and their leaving tendency follows the order. H2N– > RO– > RCOO– > Cl– Basicity  Ractivity  Resonance Effect : Due to resonance, the carbon to leaving group (L) bond acquires a double bond character due to which stabilization occurs. Now more is stabilization, lesser is the reactivity and vice-versa. As the stabilization is the least in the case of acid chloride because of high magnitude of –I effect of Cl atom. Therefore its reactivity is the most. Nucleophilic acyl substitution should be catalysed by acids becasuse the protonation of the acyl compound would facillitate step (i) for nuceleophilic attack. ACYL CHLORIDE (RCOCl) These are the derivatives of carboxylic acid in which hydroxyl (–OH) part of carboxyl group is replaced by halo group. The most reactive compound of halo leaving group is chloro compounds. METHOD OF PREPARATION Carboxylic acid chloride can be prepared by the reaction of carboxylic acid with PCl5 or SOCl2 of PCl3 or SO2Cl2. PCl5 C5H5N PCl5 R––COOH C5H5N SOCl2 C5H5N SO2Cl2 C5H5N RCOCl + HCl + POCl3 RCOCl + H3PO3 RCOCl + SO2 + HCl RCOCl + SO3 + HCl CHEMICAL PROPERTIES : 1. Acylation Reaction : 2. Acylation of aromatic compound [Friedel Craft's reaction] : R + RCOCl O anhy. AlCl3 + HCl O R + CH3COCl Acetophenone O + C6H5COCl benzophenone CARBOXYLIC ACID & THEIR DERIVATIVES 3. Catalytic hydrogenation (Rosenmund's Reaction) : O R––C––Cl + H2 RCOCl + 4H LiAlH 4 or NaBH 4 or C2H5OH+Na Pd BaSO4 RCHO + HCl R–CH2OH + HCl MECHANISM Reaction with KCN : Reaction with AgNO3 : The aliphatic acid chlorides are readily decomposed by water therefore aqueous solution of acid chloride gives white ppt. with AgNO3. Reaction of acyl chloride with diazomethane in presence of Ag2O and water. (Arndt – Eistert synthesis). This reaction convert acyl chloride to carboxylic acid with one carbon atom more : ACID ANHYDRIDES (RCOOCOR) O O R––C––O––C––R Acid anhydrides are considered to be derived from carboxylic acids by the removal of a molecule of water from two molecules of the acid. O O R––C 2R––C––OH carboxylic acid O + H2O R––C O acetic anhydride METHOD OF PREPARATION Acylation : Carboxylic acid reacts with acyl chloride in the presence of pyridine to give carboxylic acid anhydride. O O O 2R––C––OH + R'––C––Cl + O Cl R––C––O––C––OR + N N  Sodium salt of carboxylic acids also react with acyl chlorides to give : O O  O O   R––C––O––C––R + NaCl 2R––C––ONa + R––C––Cl In this reaction a carboxylate ion acts as a nucleophile and brings about a nueleophilic substitution reaction at the acyl carbon of acyl chloride. Cyclic anhydrides : By simple heating the appropriate dicarboxylic acid. This method leads to a five or six membered ring. O CH2–––––OH O 300°C CH2–––––OH CH2 O succinic acid ––C––OH O pthalic acid O + H2O O O O ––C––OH CH2 230°C O + H2O O pthalic anhydride CARBOXYLIC ACID & THEIR DERIVATIVES CHEMICAL PROPERTIES Acid anhydride are good acylating agents. Their reactions are less vigorous than the corresponding acyl halides. ESTERS (RCOOR) Ester are the derivative of the carboxylic acid in which the –OH part of the carboxylic group has been replaced by – OR group where R may be alkyl or aryl group. METHOD OF PREPARATION By reaction of acids wth alcohol or diazomethane in presence of ether. RCOOH + C2H5OH + H /H2O ether R––COOH + CH2 N2 R––COOC2H5 + H2O RCOOCH3 + N2 Ester O O R––C––Cl + C2 H5OH C5H5N R––C––OC2H5 + HCl O R––C––O O 2 O + C2H5OH C5H5N R––C––OR' + R––COOH CHEMICAL PROPERTIES Conversion to other esters : Transesterifications Conversion to amides : O R––C––OR' + HN R" R" O R––C––N R" R" + R'––OH Reaction with Grignard Reagent : Reduction of ester : Na/Mg MeCOCH2COOC2H5 LiAlH4 MeCH(OH)CH2CO2C2H5 MeCH(OH)CH2––CH2OH + C2H5OH O C LiAlH4 O C CH2 OH CH2OH O Phthalic anhydride Reaction of NH3 with keto ester : R–CO–CH2CO2C2H5 + NH3  R––C=CHCO2C2H5 + H2O NH2 MECHANISM Attack will occur at carbonyl group first because of high degree of +ve charge on carbonyl carbon atom. Acyloin condensation : MECHANISM It is the intermolecular, sodium promoted condensation of two moles of ester or the intra molecular condesation of a ester to -hydroxy ketone (acyloin). CARBOXYLIC ACID & THEIR DERIVATIVES HYDROLYSIS OF ACYL DERIVATIVES Ester hydrolysis can be carried out in mechanistic pathways A AC1 , A AC 2 , A AL1 , B AC 2 . Here A or B stand for acid or base catalysed and Ac and Al stand for acyl oxygen and alkyl oxygen cleavage and 1 or 2 stands for unimolecular or bimolecular. A AC1 : A AC2 : A AL1 : B AC2 : AMIDES (RCONH2) O R––C––NH2 METHOD OF PREPARATION Amides from Acyl chloride : Primary amines, secondary amines and ammonia all react rapidly with acid chloride to form amides. An excess of ammonia or amine is used to neutralize the HCl that would be formed otherwise. O R––COCl + RNH2  R––C––NH2 + NH4Cl R––COCl + RR'NH  RCON(R)R' + RR'N+H2Cl– N, N-disubstituted amide Amides from acid anhydride : O O R––C–– O + 2NH3 2  R––C––NH2 + RCOO NH4 CARBOXYLIC ACID & THEIR DERIVATIVES O O R––C–– O + 2R' ––NH2  R––C––NHR' + R––COONH3R' 2 From Esters (Ammonolysis) : Ester undergoes nucleophilic substitution at their acyl carbon by nucleophilic ammonia or its derivative O .. R' R––C––OR + H––N R" O .. R' R––C––N + R'OH R" By partial hydrolysis of alkyl nitriles : R––CN + H2O + H or  OH R––CO––NH2 PHYSICAL PROPERTIES All amides except formamide are crystalline solid at room temperature. They have relatively high melting and boiling point due to association of amide molecules by inter molecular hydrogen bonds. O=C––N––H O=C––N––H R H R H CHEMICAL PROPERTIES 1. Amphoteric character : Amides are very feeble bases due to involvement of pair of electron present on N atom in resonance with carboxyl groups. As a result N atom receives partial +ve charges showing feeble acidic character as well (i) Acidic character : Due to structure II amide can act as acid. O CH3––C––NH2 + CaO As acid (CH3CONH)2Ca + H2O CH3CONH2 + Na  CH3CONH–Na + 1 H 2 2 (ii) Basic Character : Due to structure I having lone pair of electrons on N atom it acts as base. CH3CONH2 + HCl  CH3CONH2+HCl– As base Acid Salt Reaction with nitrous acid : R––CONH2 + HONO  R––COOH + N2 + H2O The reaction proceeds via the attack of electrophilic species NO+ generated from HNO3. Hoffmann's Bromide Reaction : Amides react with bromine in the presence of alkali to form a primary amine having one carbon atom less than the parent amides. R––CO––NH2 + Br2 + KOH  RNH2 + K2CO3 + 2KBr + 2H2O NH2 CONH2 + Br2+ 4KOH MECHANISM 2NaOH + Br2  NaOBr + NaBr + H2O (i) (ii) Reaction with PCl5 , PCl3 or SOCl2 : O R––C––NH2 PCl5 or PCl3 or SOCl2 RCN + H2O + K2CO3+ 2KBr + 2H2O CARBOXYLIC ACID & THEIR DERIVATIVES 5. Reduction : O R––C––NH2 MECHANISM Na/C 2H 5OH R––CH2NH2 + H2O