GENERAL INFORMATION Acyl Derivatives 1 Acyl Derivatives (RCOY) ° ° q 1 Rc ace Acyl derivative Acyl portion Introduction: Acyl derivatives have the chemical formula set out first above, where the formula set out second is the acyl portion and Y represents a number of functional groups (e.g, hydroxyl, alkyl, or halide groups}. Members of different acyl derivatives are outlined in the accompanying table. Functional Group Structure — > Carboxylic acid n-b-on ° Acyl halide REX 0=1, 81.617) 2 Acid anhydride n-e-0-C-A ° Ester —¢— oR Amide nada, ee Physical Properties: . * The boiling points of acyl compounds in the same class tend to increase as the carbon chain length increases {e.g., carboxylic acids with four carbons have higher boiling points than three-carbon carboxylic acids). * The melting points of carboxylic acids, however, alternate: Acids with an even number of carbons have higher melting points than acids with one more or one less carbon. Reason: Even carbon chains pack better in the solid state and form a more stable crystal lattice. * The boiling points of compounds from different classes of acyl derivatives vary depending on the strength of intramolecular forces. For instance, carboxylic acids have higher boiling points than esters because of thePr * Carboxylic acids are acidic; acyl halides and anhydrides hydrolyze in water to give acidic solutions; esters and amides are neutral. ‘* Solubility in water is also dircctly related to the strength of the hydrogen bond between water and solute. ‘© Most of the reactions of acyl compounds center around the polarized C=O bond, where the carbon atom is electrophilic and the oxygen is nucleophilic. Some of the common reactions are nucleophilic acyl substitu- tion (also called an addition elimination reaction), carbonyl d-substitution, and carbonyl condensation. An illustration of nucleophilic acyl substitution is shown #8 5 here (see Acyl Derivatives 2 for details). * Reactivity of different classes of acyl derivatives depends on two factor 1. Polarity factor: Acyl derivatives with strong polarity in the C=O bond are more reactive than those with weak polarity. This factor explains the following observed reactivity among acyl derivatives. ‘Acyl derivative: Amide < Ester < Acid anhydride < Acid halides Reactivity: Less == More —— | ¢ Sb 6 X= LBL 2. Steric factor: Within the same class of acyl derivatives, compounds with more exposed and less hindered carbonyl groups tend to be more reactive. Members of acyl derivatives undergo More reactive Less roacive interconversion (e.g., amides to esters, or ° i a i i 1 woc-e-x > H-G-bK > RCo > Rex | 4 Sythe wel inercomerion fey derivatives vice versa.}. In general, classes of acy] derivatives a with high reactivity can be converted to classes oa aman ges [ea with low reactivity. However, the reverse usually ° ° ° . does not occur (classes with low reactivity do not - produce classes with high reactivity). The only. swing HE * ~ * * exception is in the case of amides. pace se |e 5 = °NUCLEOPHILIC ACYL SUBSTITUTION REACTION Keys: Acyl Derivatives 2 1. This is one of the most important reactions of carbonyl compounds; carboxylic acids, esters, amides, acyl anhydrides, and acyl halides all can undergo this reaction. 2. The reaction is also known as the acyl transfer reaction. 3. In essence, the reaction leads to replacement of the leaving group (X) on the carbonyl compounds with an incoming nucleophile (Nu:), thereby forming a new class of carbonyl compound. 4. The reaction proceeds through two stages: (a) formation of a tetrahedral intermediate and (b) breakdown of the intermediate. The exact mechanism of the reaction varies slightly depending on the starting carbonyl substrates, nucleophiles, and leaving group (sce Table below). Starting Carbonyl Nucleophiles Leaving Group ‘Mechanism Compound Acyl halide Anions, neutral nucleophiles Halide ion “Type 1 (see back for details) Acyl anhydride ‘Anions, neutral nucleophiles ‘Acetate ion Type 1 (see back for details) Ester (in base) ‘Alkoxide ions, hydroxide ions, Alkoxide ion ‘Type 1 (see back for details) ammonia, amines ‘Amide (in base) Alkoxide ions, hydroxide ions, Amide ion ‘Type 1 (sce back for details) ammonia, amines Carboxylic acid Neutral nucledphiles: alcohols, Water “Type 2 (sce back for details) ‘ammonia, water Ester (in acid) Neutral nucleophiles: alcohols, Alcohol ‘Type 2 (sce back for details) ammonia, water [Amide (in acid) ‘Neuteal nucleophiles: alcohols, Ammonia “Type 2 (sce back for details) ammonia, water * This table serves only as a general guide. Please see each reaction in later sections for more details.Mechanisms: ‘Type 1 (see Acyl Halides 2 for an example) Stage I 1, Nuclophile (Nu:) attacks the carbonyl compound to form a tetrahedral intermediate. Stage II 2. Oxygen donates a pair of electrons to re-form the C=O double bond. The leaving group (X) is expelled. A new class of carbonyl compound is formed. Type 2 (see Carboxylic Acids 6 for an example) Stage I 1. Oxygen atom is first protonated to facilitate the subsequent carbonyl attack by a neutral nucleophile. 2. Nucleophilic attack on the carbonyl carbon produces on a tetrahedral intermediate. nb I Stage II Now 3. Either proton addition or transfer occurs, making 5 the leaving group a better leaving group. Proto 4. Elimination of the leaving group occurs. ~ rancor 5. Deprotonation step takes place to form the new class of carbonyl compound. a 4 on 1 ® i o Sha. poem BS ane SS ney