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SCH 206 Course Outline Aldehydes and Ketones; Carboxylic Acids; Carboxylic Acids Derivatives;

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SCH 206 SCH 206 Course outline Aldehydes and Ketones; Carboxylic Acids; Carboxylic Acids derivatives; Amines R1 N R2 and Phenols R3 Structure, Nomenclature, Synthesis and Dr. Solomon Derese Reactions 1 SCH 206 Dr. Solomon Derese; Chemistry Department Room 118; [email protected] Recommended text books 1. Organic Chemistry, John McMurry 2. Organic Chemistry, Francis Carry 3. Organic Chemistry, Solomons T.W.G. 2 Dr. Solomon Derese SCH 206 Science is the knowledge of consequences and dependence of one fact upon another Thomas Hobbes (1588–1679) 3 Dr. Solomon Derese O SCH 206 Carbonyl Compounds R Z Two broad classes of compounds contain the carbonyl group: I. Compounds that have only carbon and hydrogen atoms bonded to the carbonyl group (Aldehydes and Ketones). O R R' Aldehyde Ketone An aldehyde has at least one H atom bonded to the carbonyl group. A ketone has two alkyl or aryl groups bonded to the carbonyl group. 4 Dr. Solomon Derese SCH 206 II. Compounds that contain an electronegative atom bonded to the carbonyl group (Carboxylic acids and their derivatives). Each of these compounds contains an electronegative atom (Cl, O or N) capable of acting as a leaving group. The presence or absence of a leaving group on the carbonyl carbon determines the type of reactions these compounds undergo. 5 Dr. Solomon Derese SCH 206 Nature of the Carbonyl Group The double bond between carbon and oxygen is similar to an alkene C=C double bond. The carbonyl carbon is sp2-hybridized and forms three bonds. R1 R2 R3 R4 Alkene 6 Dr. Solomon Derese SCH 206 Alkene Carbonyl p-bond p-bond d-bond d-bond C C 120° 120° C O sp2 orbital sp2 orbital 2p orbital 2p orbital The C=O double bond is similar to a C=C double bond, except that it is shorter, stronger, and polarized. Bond Bond distance Bond energy Dipole moment C=C 134 pm 611 KJ/mol 0.3 D C=O 122 pm 745 KJ/mol 2.5 D 7 Dr. Solomon Derese SCH 206 The difference between the alkene double bond and the carbonyl double bond arises from the different electronegativities of the elements involved. Oxygen is more electronegative than carbon (3.5 compared with 2.5); therefore, a carbon-oxygen double bond is polar, with oxygen bearing a partial negative charge and carbon bearing a partial positive charge. The carbon carries a partial positive charge, is an electrophilic site, and reacts with nucleophiles. Conversely, oxygen atom carries a partial negative charge, is a nucleophilic site, and reacts with electrophiles. 8 Dr. Solomon Derese SCH 206 Electronegativity Nucleophilic (electron rich) Reacts with electrophiles, e.g. H+ Electrophilic (electron deficient) Reacts with nucleophiles Uncrowded SP2 carbon The electrophilicity of a carbonyl group derives from resonance effects as well as inductive effects. 9 Dr. Solomon Derese SCH 206 The reactivity of carbonyl compounds is due to the polarity of the carbonyl group that results from oxygen being more electronegative than carbon. The carbonyl carbon is therefore electron deficient (an electrophile). So we can safely predict that it will be attacked by nucleophiles. As a result, carbonyl compounds react with nucleophiles. :Nu Planar (sp2) Tetrahedral intermediate (sp3) 10 Dr. Solomon Derese SCH 206 When a nucleophile adds to the carbonyl carbon the weakest bond in the molecule - the carbon- oxygen double bond (p-bond) breaks forming a tetrahedral intermediate. When a carbonyl group is attacked by a nucleophile, the carbon atom undergoes a change in hybridization (sp2 to sp3) and geometry (planar to tetrahedral). The outcome of nucleophilic attack, however, depends on the identity of the carbonyl starting material. It depends on whether Z is a leaving group or not. 11 Dr. Solomon Derese SCH 206 I. Reactions of carbonyl compounds when Z is not a leaving group – Nucleophilic addition Nucleophilic Addition Reaction Aldehydes (Z = H) and ketones (Z = R) undergo nucleophilic addition as neither H or R are leaving groups. 12 Dr. Solomon Derese SCH 206 Mechanism of Nucleophilic Addition Reaction Step I: Nucleophilic attack Tetrahedral intermediate The nucleophile (:Nu–H) attacks the electrophilic carbonyl. As the new bond to the nucleophile forms, the p bond is broken, moving an electron pair out on the oxygen atom. This forms an sp3 hybridized intermediate. 13 Dr. Solomon Derese SCH 206 Step II: Proton transfer OH R1 H (R2) Nu Proton (Hydrogen) transfer from the positively charged nucleophile to the negatively charged oxygen forming neutral addition product. The net result is that the p bond is broken, two new d bonds are formed, and the elements of H and Nu are added across the p bond. 14 Dr. Solomon Derese SCH 206 Stereochemistry of the Nucleophilic Addition Reaction H-Nu: Racemic mixture H-Nu: The carbonyl carbon is planar and nucleophiles can attack it from either side (bottom as well as top face) equally. As a result, the carbonyl addition product will consist of a racemic mixture. Dr. Solomon Derese SCH 206 II. Reactions of carbonyl compounds when Z is a leaving group – Nucleophilic Acyl substitution Z= –OH (carboxylic acid), –OR (ester), –Cl (acid chloride), –NH2 (amide), or –OCOR (acid anhydride) Nucleophilic Acyl Substitution Reaction Carbonyl compounds that contain leaving groups (electronegative elements) undergo Nucleophilic Acyl Substitution Reaction. 16 Dr. Solomon Derese SCH 206 Mechanism of Nucleophilic Acyl Substitution Reaction Step I: Nucleophilic attack Tetrahedral intermediate The nucleophile (:Nu–H) attacks the electrophilic carbonyl, forming an sp3 hybridized intermediate. This step is identical to nucleophilic addition. 17 Dr. Solomon Derese Step II: Loss of a leaving group SCH 206 O Z R1 Z: Nu H Because the intermediate contains an electronegative atom Z which can act as a leaving group. To do so, an electron pair on oxygen re-forms the p bond, and Z leaves with the electron pair in the C – Z bond. The net result is that Nu replaces Z, a nucleophilic substitution reaction. This reaction is called Nucleophilic Acyl Substitution. 18 Dr. Solomon Derese SCH 206 A compound that has an sp3 carbon bonded to an oxygen atom generally will be unstable if the sp3 carbon is bonded to another electronegative element. The tetrahedral intermediate, therefore, is unstable because Z and Nu are both electronegative atoms. For an aldehyde or ketone to undergo nucleophilic acyl substitution reaction, the tetrahedral intermediate would need to eject a hydride ion (H:-) or an alkanide ion (R:-). Both are very powerful bases, and both are, therefore, very poor leaving groups. 19 Dr. Solomon Derese SCH 206 Reactions like this do not occur with aldehydes and ketones 20 Dr. Solomon Derese SCH 206 Comparison of Carbonyl Reaction Types I. Nucleophilic addition and nucleophilic acyl substitution involve the same first step— nucleophilic attack on the electrophilic carbonyl carbon to form a tetrahedral intermediate. II. The difference between the two reactions is what then happens to the intermediate. III. Aldehydes and ketones cannot undergo substitution because they do not have a good leaving group bonded to the newly formed sp3 hybridized carbon. Dr. Solomon Derese 21 SCH 206 Reactivity of carbonyl compounds The reactivity of the carbonyl group towards nucleophiles is dependent on: I. The electrophilicity of the carbonyl carbon The relative reactivities of carbonyl O compounds with nucleophiles is mainly attributed to the amount of positive charge R1 Z on the carbonyl carbon. A greater positive charge means higher reactivity. If the partial positive charge is dispersed throughout the molecule, then the carbonyl compound is more stable and less reactive. 22 Dr. Solomon Derese SCH 206 In general electron withdrawing groups increase the electrophilicity of the carbonyl carbon while electron donating groups decrease the electrophilicity of the carbonyl carbon. II. The accessibility of the carbonyl carbon Sterically hindered carbonyl compound react slower with nucleophiles as a result aldehydes (one alkyl group) are more reactive than ketones (two alkyl groups) . 23 Dr. Solomon Derese SCH 206 In general, aldehydes are more reactive than ketones toward nucleophilic attack. This observation can be explained in terms of both steric and electronic effects. Aldehydes Ketones O R1 R2 Less steric hindrance Only one R stabilizes Two R’s increase Two R’s stabilizes the with only one R group the positive charge. steric hindrance positive charge. Less crowded Less stable More crowded More stable Aldehydes—more reactive Ketones—less reactive 24 Dr. Solomon Derese SCH 206 Steric effect The two R groups bonded to the ketone carbonyl group make it more crowded, so nucleophilic attack is more difficult. Electronic effect Recall that alkyl groups are electron donating. The two electron-donor R groups stabilize the partial charge on the carbonyl carbon of a ketone, making it more stable and less reactive. The d+ charge of an aldehyde is less stabilized than a ketone. As a result, aldehydes are more electrophilic than ketones and therefore more reactive. 25 Dr. Solomon Derese SCH 206 Thus, carbonyl compounds containing electron- withdrawing groups are the most electrophilic and the most reactive, followed in turn by formaldehyde, other aldehydes, and finally ketones. Most reactive Least reactive Aromatic carbonyl compounds are less reactive than aliphatic carbonyl compounds, for its delocalized p orbitals can also act as electron source. 26 Dr. Solomon Derese SCH 206 The bulkier the alkyl group the less reactive. > > This is due to the crowding that results by adding nucleophiles to the carbonyl carbon. 27 Dr. Solomon Derese Assignment 1 SCH 206 Which ones are more reactive towards nucleophilic addition, explain. a) b) 28 Dr. Solomon Derese SCH 206 Carboxylic acid and its derivatives differ greatly in their reactivity towards nucleophilic acyl substitution reaction. They have a generalized structure as follows: This resonance contribution leads to: a) Partial double bond character on the C-Y bond, and b) Reduced partial positive charge at the carbonyl carbon.
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