2. Aldehydes and Ketones Handout # 7 Winter 2015/2016 (N. Noureldin)

3. Carbonyl group p-Orbital Picture Resonance Picture 3.1 Carbonyl group: structure, reactivity and molecular orbital model, polarity and polarization 3Aldehydes and Ketones (Alkanal & Alkanone)

4. 3 Oxidation of alcohols Secondary alcohols can be oxidized to ketones Primary alcohols can be oxidized to aldehydes (absence of water!) Ozonolysis of alkenes gives aldehydes or ketones Typical methods of the synthesis of Aldehydes and Ketones (Review) Hydration of terminal alkynes gives methyl ketones. OR KMnO 4

5. 4 The preparation of alcohols from aldehydes or ketones with the same number and arrangement of carbon atoms. 3.2 General array of reactivities Generally speaking, aldehydes are less stable than ketones hence, aldehydes are more reactive. Among others, the steric factors contribute to the greater reactivity of an aldehyde

6. 5 Nomenclature: 1)Aldehydes (alkanal)Give #1 to Formula IUPACCommon Methanal Formaldehyde Ethanal Acetaldehyde PropanalPropanaldehyde 3-Chloropropanal 3.3 Nomenclature and trivial names of aldehydes and ketones 2) Ketones (alkanone) givethe lowest # Formula IUPAC Common PropanoneAcetone Butanone Methyl ethyl ketone Alkanedione 2, 3-Pentanedione 2, 4-Pentanedione

7. 6 1, 4-Cyclohexanedione 2, 3, 7-Trimethyl-5-decanone (Alkenone,CO lowest #) 4-Penten-2-one 3-Pentanone 2-Pentanone

8. They are strongly polar compounds hence, their B.P. are higher than corresponding alkanes and ethers. However, due to the absence of hydrogen bonding, B.P. of aldehydes and ketones are lower than corresponding alcohols and carboxylic acid. 7 Carbonyl group 3.4 Physichochemical properties 3.5 Enolisation (Tautemerization)

9. 3.6 Some typical reactions of aldehydes and ketones: Nucleophilic Additions Reactions

10. 3.6.1

11. 10 Under anhydrous conditions, dissolving an aldehyde in an alcohol causes the establishment of an equilibrium between the two and a new compound called “hemiacetal”. The essential structure features of a hemiacetal are an –OH and –OR groups attached to the same carbon atom (and since this carbon atom came from an aldehyde, this carbon also has one hydrogen atom attached to it). Most open-chain hemiacetals are not sufficiently stable to isolate. However, cyclic ones with 5 or 6 membered rings are usually much more stable. Hemiacetals and Hemiketals very high concentration 3.6.2

12. 11 Ketones undergo similar reactions when are dissolved in an alcohol producing also unstable products in open-chain compounds “hemiketals” Most simple sugars exist primarily in a cyclic hemiacetal form. Glucose is an example. Hemiketals Mechanism of hemiketal formation from ketone is similar to the formation of hemiacetal from an aldehyde. Conversion of Aldehydes / Ketones to Acetals / Ketals through Hemiacetals / Hemiketals intermediates It should be emphasized that acid catalysis is required to make an acetal OR a ketal. Why? A: the mechanism

13. 12 Mechanism All steps are reversible 1) Formation of Hemiacetals/Hemiketals 2) Hemiacetals /Hemiketals to Acetals/Ketals As expected, excess ROH and /or removal of water shifts equilibrium to product. On the other hand addition of water converts the product back into the carbonyl group.

14. 13 Mechanism

15. 14 It should be noted that Ketal formation is not favoured when ketones are treated with simple alcohol and gaseous HCl. Fortunately, cyclic ketal formation is favoured when a ketone is treated with an excess of an anhydrous1,2 diol and trace of anhydrous acid. In conclusion, all steps included in the conversion of an aldehyde or ketone to acetal or ketal via hemiacetal or hemiketal as intermediates, are reversible. Performing the reaction in large excess of an anhydrous alcohol and a small amount of an anhydrous acid will strongly favour the formation of acetals or ketal. On the other hand, in the presence of large amounts of water and small amount of an acid, acetals or ketal could be converted back to the carbonyl compounds. 3.6.3 Acetals as protecting groups

16. 15 Because of this property, acetals and cyclic ketals give us a convenient method for protecting aldehyde and ketone groups from undesired reactions in basic solutions. We can convert an aldehyde or ketone to acetal or cyclic ketal, carry out a reaction on some other part of the molecule, and then hydrolyze the acetal or ketal with aqueous acid. As an example, let us consider the problem of converting Keto groups are more easily reduced than ester groups. Any reducing agent such as LiAlH 4 or H 2 /Ni that will reduce the ester of A will reduce the keto group as well. However, if we protect the keto group by converting it to a cyclic ketal (the ester group does not react), we can reduce the ester group in basic solution without affecting the cyclic ketal. Then hydrolysis the ketal yields the desired product as follows: Acetals / Cyclic Ketals are inert to basic and reducing reagents.

17. 16

18. 17 Some reactions of ammonia (primary amine)derivatives with carbonyl compounds. NH 3  ammonia; NH 2 G  derivative of ammonia Addition of Derivatives of Ammonia General Equation: 3.6.4

19. 18 Mechanism Step 1: Addition Step 2: Acid-catalyzed E1 dehydration Mechanism- Imines formation; compounds with C=N.

20. 3.6.5

22. 3.6.6 Beckmann Rearrangement: conversion of Oximes to Amides Beckmann rearrangement is an acid-induced rearrangement of oximes to give amides. In this reaction an electropositive nitrogen is formed that initiates an alkyl migration (rearrangement). Oximes generally have a high barrier to inversion, and accordingly this reaction is envisioned to proceed by protonation of the oxime hydroxyl, followed by migration of the alkyl substituent.

23. Mechanism Alkyl migration - H + Recall the addition of water to Alkynes : Tautomerism * *