6-Carboxylic Acids PDF

Carboxylic Acids Physical Properties The melting points and boiling points of carboxylic acids are higher than those of hydrocarbons and oxygen-containing organic compounds of comparable size and shape and indicate strong intermolecular attractive forces....

Carboxylic Acids Physical Properties The melting points and boiling points of carboxylic acids are higher than those of hydrocarbons and oxygen-containing organic compounds of comparable size and shape and indicate strong intermolecular attractive forces. O OH O OH 2-methylbut-1-ene butan-2-one butan-2-ol propionic acid bp (1 atm) 31 oC 80 oC 99 oC 141 oC Acidity of Carboxylic Acids Carboxylic acids are the most acidic class of compounds that contain only C, H, and O. This is due to the inductive effect (I) of the carbonyl group (C=O). Inductive Effect: Permanent polarization along the carbon chain due to the presence of electron donating or electron withdrawing group. Types of inductive effect + I effect – when the substituents are electron donating groups (e.g., CH3 , C2H5, …..etc) e.g. – I effect- when the substituents are electron withdrawing groups (e.g., - NO2, –CN ˃F, Cl , Br, I,…etc.) e.g. 124  Inductive Effects and Acidity The presence of electrondonating group in the acid decreases the acidity. On the other hand, the presence of electronwithdrawing group in the acid increases the acidity. O O O O Acid FCH2 C OH ClCH2 C OH ICH2 C OH CH3 C OH 2.59 2.86 3.12 4.76 Pka Increase in the acidity strength The inductive effect and the distance The inductive effect is dependent on the distance between the substituent group and the main group that react. That is, as the distance of the substituent group increases the Inductive effect weakens or decreases. 125  The resonance effect (R) of the carbonyl group (C=O). Electron delocalization, expressed by resonance between the following Lewis structures, causes the negative charge in acetate to be shared equally by both oxygens. Electron delocalization of this type is not available to ethoxide ion. 126  Synthesis of Carboxylic Acids By the carboxylation of Grignard reagents Grignard reagents (RMgX) react with carbon dioxide (CO2) to yield magnesium salts of carboxylic acids, Acidification carboxylic acids By the hydrolysis of nitriles (alkyl cyanides) 1ry and 2ry alkyl halides may be converted to the next higher carboxylic acid by a two- step synthetic sequence involving the preparation and hydrolysis of nitriles. By Oxidation of 1ry alcohols 127  Reactions of carboxylic acids: 1- Formation of acyl chlorides: Thionyl chloride (SOCl2) reacts with RCOOH gave RCOCl. 2- Reduction of RCOOH using Lithium Aluminum hydride (LiAlH4) are reduced to 1ry alcohols 3- Esterification: Carboxylic acids (RCOOH) reacted with alcohols (ROH) In the presence of an acid catalyst to give favor the ester by H2O removal. 4- α-Halogenation of Carboxylic Acids (Hell–volhard–zelinsky) reaction: The introduction of α –X substituent at the α-C atom requires a treatment of RCOOH with X in the presence of red Phosphorous (P) or phosphorus trichloride (PCl3) as a catalyst 128 This reaction is sometimes carried out by using P instead of PCl3 (Phosphorus reacts with X2 to yield PX3). Carboxylic Acid Derivatives  We can readily convert a more reactive acid derivative into a less reactive one  Reactions in the opposite sense are possible but require more complex approaches 129  Reactions of Acid Halides  Nucleophilic acyl substitution  Halogen replaced by OH, by OR, or by NH2  Reduction yields a primary alcohol  Grignard reagent yields a tertiary alcohol Reaction of Acyl chlorides with ammonia and amines to form amides. Hydrolysis Acyl chlorides react with water to yield carboxylic acids. 130  Reactions of Acid Anhydrides Similar to acid chlorides in reactivity R1OH O O + R OR1 R OH ester carboxylic acid O O O R2NH O R O R R R N + R OH R Anhydride Amide carboxylic acid O H2O 2 R OH carboxylic acid 131  CH3OH O O H3C OCH3 + H3C OH methyl acetate acetic acid O O O O NH3 H3C O CH3 H3C NH2 + H3C OH Acetic anhydride acetamide acetic acid O H2O 2 H3C OH acetic acid Reactions of Esters Less reactive toward nucleophiles than are acid chlorides or anhydrides Cyclic esters are called lactones and react similarly to acyclic esters 132  Preparation of Esters Reactions of Esters Reaction of two Grignard reagents with Esters to produce tertiary alcohols Reduction of esters with lithium aluminum hydride (LiAlH4) to yield two alcohols O LiAlH4 Example: OH + HO O propyl acetate ethanol propan-1-ol 133  Reaction of Esters with ammonia and amines to form amides. Hydrolysis of Ester hydrolysis catalyzed either by acids or by bases to produce carboxylic acid and alcohol. Preparation of Amides Amides are prepared by acylation of ammonia and amines with acyl chlorides, anhydrides, or esters. O O O O R Cl + RNH2 R NHR + HCl Ex H3C Cl + NH3 H3C NH2 + HCl Acid chloride Amide acetyl chloride acetamide O O O O O O R O R + RNH2 R NHR + RCOOH Ex H3 C O CH3+ CH3NH2 H3C NHCH3 + CH3COOH Acid anhydride Amide acetic anhydride N-methylacetamide O O O H3C O NH CH3 R OR1 + RNH2 R NHR + R1OH Ex H3C OCH3 + H3C N + CH3OH H3C CH3 Ester Amide methyl acetate N,N-dimethylacetamide 134 Hydrolysis of Amides Amides are cleaved on heating in the presence of strong acids or bases to produce an amine and a carboxylic acid. Hofmann degradation On treatment with bromine in basic solution, amides of the type undergo an interesting reaction that leads to amines. O O 1 OH R1 OH R + Br2 Ex H3C NH2 + Br2 CH3NH2 + CO2 R N R N + CO2 R1 R1 Reduction with LiAlH4 Q: Convert acetic acid into methylamine and ethylamine 135  Preparation of Nitriles Nucleophilic substitution by cyanide ion with alkyl halides to give alkyl nitriles: Cyanohydrin formation: by addition of HCN to the carbonyl group of aldehydes and ketone Alkyl nitriles are prepared by dehydration of amides. Reactions of Nitriles: Hydrolysis: Acid nitriles hydrolysis yields ammonium ion and carboxylic acid, in aqueous acid medium (H+) 136 In aqueous base, hydroxide ion abstracts a proton from the carboxylic acid: Nitriles are susceptible to nucleophilic addition. In their hydrolysis, water adds across the C–N triple bond: 137