hem A225 Notes Page 67 I. Introduction hapter 20: Aldehydes and Ketones Aldehydes and ketones contain a carbonyl group (=) with no other heteroatoms attached. An aldehyde has at least one hydrogen attached; a ketone has only carbon groups attached. R H R R' aldehyde abbreviation: R H ketone abbreviation: R () R The three-dimensional structure and hybridization of aldehydes and ketones is shown below: R R' R R' lone pairs in sp 2 hybridized orbitals trigonal planar sp 2 hybridized pi bond All = compounds have a minor contributing resonance structure that heavily influences their chemistry: R R' R R' electrophiles react here nucleophiles react here Review: xidation States of arbon (handout on next page)
xidation State Name Representative Structure Number of Bonds to Heteroatoms (, N, F, P, S, l, Se, Br, I) Direction of hange in Types of Reactions Most Reduced xidation States of arbon Most xidized alkane alcohol aldehyde/ketone carboxylic acid carbon dioxide H 0 1 2 3 4 Reduction (increase bonds to H or, decrease bonds to heteroatoms) Heteroatom Exchange H xidation (decrease bonds to H or, increase bonds to heteroatoms) hem A225 Notes h 20: Aldehydes and Ketones Page 68
hem A225 Notes h 20: Aldehydes and Ketones Page 69 II. Nomenclature of Aldehydes and Ketones A. IUPA Nomenclature of Aldehydes 1) Find the longest carbon chain which contains the aldehyde (H) carbon. 2) ount the number of carbons in this chain and determine the parent stem name. 3) Add the suffix -anal. 4) Number the carbon chain starting from the aldehyde (H) carbon (H carbon is carbon one). 5) Add substituent names, with appropriate numbers, in front of the aldehyde name. B. Special ommon Names of Aldehydes (MEMRIZE): H H H H H 3 formaldehyde acetaldehyde benzaldehyde
hem A225 Notes h 20: Aldehydes and Ketones Page 70. IUPA Nomenclature of Ketones 1) Find the longest carbon chain which contains the carbonyl (=) carbon. 2) ount the number of carbons in this chain and determine the parent stem name. 3) Add the suffix -anone. 4) Number the carbon chain starting from the end closest to the carbonyl (=) carbon. 5) Indicate the position of the carbonyl (=) carbon by adding the number, separated by dashes, in between the stem name and the -one suffix (ie. stem-#-one). 6) Add substituent names, with appropriate numbers, in front of the ketone name. 7) In complex molecules, the carbonyl (=) carbon can be named as an oxo group. D. ommon Nomenclature of Ketones (Systematic) 1) Name each carbon group attached to the carbonyl (=) carbon as an alkyl group. 2) List the alkyl groups, separated by spaces, in front of the word ketone. E. Special ommon Names of Ketones (MEMRIZE) H 3 H 3 H3 acetone acetophenone benzophenone
hem A225 Notes h 20: Aldehydes and Ketones Page 71 III.Synthesis of Aldehydes and Ketones A. xidation of Alcohols (to aldehydes and ketones) (Review Section 13.10) bserved Reaction: 1 o Alcohols to Aldehydes H R H P (r 3, Hl, pyridine) R H H 1 o alcohol P = pyridinium chlorochromate aldehyde bserved Reaction: 2 o Alcohols to Ketones H Na 2 r 2 7, H 2 S 4 R R' R R' (Jones reagent) H 2 o alcohol ketone Jones reagent can t be used to make aldehydes; it oxidizes them to carboxylic acids. B. zonolysis of Alkenes (Review section 9.11) bserved Reaction R 1 H R3 1) 3 R 2 R 1 2) H 3 SH 3 H R3 R 2 An alkene carbon with a hydrogen attached becomes an aldehyde. If the alkene carbon has two carbon groups attached, it forms a ketone.. Friedel-rafts Acylation (Review section 19.6) bserved Reaction R l R All 3
hem A225 Notes h 20: Aldehydes and Ketones Page 72 D. Hydration of Alkynes (Review section 10.7) bserved Reaction HgS 4, H 2 S 4, H 2 R R R H 2 R Works best to use symmetric alkynes. Unsymmetric alkynes form two regioisomers. E. Hydroboration of Alkynes (Review section 10.7) bserved Reaction H 1) Sia 2 BH 2) H 2 2,NaH H H H F. Alkyl uprate oupling to Acid hlorides bserved Reaction Formation of R 2 uli (lithium dialkylcuprates)
hem A225 Notes h 20: Aldehydes and Ketones Page 73 uprates allow R: to act like a nucleophile on alkyl halides and acyl halides: ther R: reagents (Grignards and alkyllithiums) are too basic and do elimination instead of substitution when reacted with alkyl halides: IV.Reactivity of Aldehydes and Ketones A. Reaction with Strong Nucleophiles Strong nucleophiles are strongly basic and usually have a negative charge. The negative charge of the strong nucleophile is attracted to the δ+ charge on the carbon of the carbonyl (=) group. When the nucleophile makes a bond to the = carbon, the pi bond is broken and the electrons from the bond are moved up to the oxygen: The product is called the tetrahedral intermediate. The tetrahedral intermediate is very unstable because the electrons and negative charge on oxygen are pushing on the tetrahedral carbon (this is sometimes called electron pressure).
hem A225 Notes h 20: Aldehydes and Ketones Page 74 If there is a reasonable leaving group on the tetrahedral carbon, it will be pushed out by the electron pressure and the = pi bond will be reformed. In general, any group other than a carbon group or a hydrogen can be pushed off the tetrahedral intermediate. If there is more than one possible leaving group, then the least basic group will be pushed out. Therefore, aldehydes and ketones will react by addition of strong heteroatom nucleophiles (such as H or l ); however, these nucleophiles are quickly pushed back off the tetrahedral intermediate, so no net reaction is observed. B. Reaction with Weak Nucleophiles Many weakly basic, uncharged species (like alcohols [RH] and water) can behave like nucleophiles. Most of these are also excellent leaving groups. Because these weak nucleophiles are uncharged, they are much less strongly attracted to the carbonyl (=) carbon. Because these weak nucleophiles are good leaving groups, they are rapidly pushed off the tetrahedral intermediate if they do add to the =.
hem A225 Notes h 20: Aldehydes and Ketones Page 75 To help weak nucleophiles add to carbonyls (=), we usually must add an acid catalyst. The acid catalyst protonates on the = oxygen. This creates a positive formal charge on the = oxygen. As a result, the oxygen more strongly attracts electrons, which increases the amount of δ+ charge on the = carbon. The increased δ+ charge on the = carbon increases the reactivity of the =, and helps attract the weak nucleophile. The proton on oxygen also stabilizes the tetrahedral intermediate, reducing the electron pressure and helping the weak nucleophile stay bonded to the carbon.. Relative Reactivity of Aldehydes and Ketones Aldehydes are more reactive than ketones to addition of nucleophiles. There are two factors that make aldehydes more reactive than ketones: 1) Aldehydes are less sterically hindered than ketones. 2) The δ+ charge on the aldehyde = carbon is larger than on the ketone = carbon, because the aldehyde has fewer electron donating carbon groups attached.
hem A225 Notes h 20: Aldehydes and Ketones Page 76 V. Reactions of Aldehydes and Ketones A. xygen Addition (formation of hydrates and acetals) bserved Reactions Mechanism [Very important!] To understand and remember the mechanism of heteroatom exchange reactions, we will break them into phases that describe the overall changes. For this mechanism, there are three phases: 1) Add the first alcohol (Add RH) 2) Remove = oxygen (Remove H) 3) Add the second alcohol (Add RH) Each of these phases will have several steps that will always occur as part of a pattern. For example, any time that we remove an H (Phase 2), we will use the same 3 types of step in the same order. We will learning the mechanism by learning the patterns in the three phases. The mechanism is a series of reversible, equilibrium driven steps. In many steps there are other possible reactions; however, these don t lead to any products, and are eventually reversed back to the product forming pathway. Sometimes, one of the substeps of a phase will be skipped.
hem A225 Notes h 20: Aldehydes and Ketones Page 77 Phase ne: ADD RH (add weak nucleophile) Steps: Protonate = --> Add nucleophile --> Make stable (remove H + ) Protonating the = oxygen activates = for addition of the weak nucleophile Phase Two: REMVE H Steps: Protonate H --> Remove LG --> (Make stable) Protonation of H makes it into a good leaving group (LG) The make stable step is skipped because there is no H + available to remove Phase Three: ADD RH Steps: (Protonate =) --> Add Nu: --> Make stable The first step is not needed in this case, because the intermediate is already activated by the carbon group, and is still unstable from the end of phase 2.
hem A225 Notes h 20: Aldehydes and Ketones Page 78 Hemiacetals are usually unstable, especially in base. However, cyclic hemiacetals are reasonably stable (found in sugar chemistry, for example glucose). Acetals can be converted back to ketone/aldehyde and alcohols using acid in water (H 3 + ). This is called acid-catalyzed hydrolysis of acetals. (bserved reaction)
hem A225 Notes h 20: Aldehydes and Ketones Page 79 The mechanism of hydrolysis is exactly the same as the mechanism of formation, just in reverse. As an exercise, write out the mechanism of acid-catalyzed hydrolysis of acetals in the space below: By using a diol (for example, HH 2 H 2 H [ethylene glycol]), cyclic acetals can be formed: yclic acetals are often used as protecting groups, to prevent a = from doing an unwanted reaction. They can be removed by acid-catalyzed hydrolysis:
hem A225 Notes h 20: Aldehydes and Ketones Page 80 B. Nitrogen Addition (formation of imines, hydrazones, oximes) bserved Reaction (general) Requires that the nitrogen atom have at least two hydrogens attached (we will study the reaction when there is only one hydrogen on nitrogen in a later chapter). Different Z groups lead to similar products with different names: Z Group H 2 N Z Name Product Name Product Structure R or H amine H 2 N R imine N R H hydroxylamine H 2 N H oxime N H NH 2 hydrazine H 2 N NH 2 hydrazone N NH 2 NH Ph phenylhydrazine, H 2 N NH Ph phenylhydrazone N NH Ph
hem A225 Notes h 20: Aldehydes and Ketones Page 81 Mechanism If we analyze the change in structure from the reactant to the product, we see two major changes. A nitrogen group has been added, and the oxygen has been removed. This implies two phases: Add RNHZ --> Remove oxygen Phase ne: Add RNHZ Protonate = --> Add Nu: --> Make Stable Phase Two: Remove oxygen Protonate H --> Remove LG --> Make Stable =N can be converted back to = by acid-catalyzed hydrolysis. Mechanism is exact reverse of mechanism for formation of =N from =. Practice writing the reverse mechanism on a separate page.
hem A225 Notes h 20: Aldehydes and Ketones Page 82. Hydride Addition (to form alcohols) (review section 13.4) bserved Reactions Formal Mechanism: Sodium borohydride (NaBH 4 ) and lithium aluminum hydride (LiAlH 4 ) are sources of H: (hydride). Hydride is a hydrogen nucleophile. It reacts with the = carbon: NaBH 4 only reacts with ketones and aldehydes. LiAlH 4 is more reactive; it will reduce aldehydes and ketones, and also will reduce esters, carboxylic acids, amides, and nitriles.
hem A225 Notes h 20: Aldehydes and Ketones Page 83 D. rganometallic Additions (Grignard Reagents) (Review section 13.6) bserved Reactions Mechanism: Formation of Grignard reagents and alkyllithiums (bserved Reactions) Restrictions on Grignard reagents and alkyllithiums: arbanions (R: ) are very strong bases. They will do acid-base reaction and deprotonate H, N H, S H, and P H bonds. This irreversibly destroys the carbanion. Therefore, H, N H, S H, or P H bonds can t be present in the Grignard reagent/alkyllithium or in the carbonyl substrate.
hem A225 Notes h 20: Aldehydes and Ketones Page 84 E. yanide Addition (formation of cyanohydrins) bserved Reaction Mechanism yanohydrin formation is readily reversed by treating the cyanohydrin with base:
hem A225 Notes h 20: Aldehydes and Ketones Page 85 F. Wittig Reaction (formation of alkenes) bserved Reaction Mechanism Formation of Wittig Reagent from triphenylphosphine (PPh 3 )
hem A225 Notes h 20: Aldehydes and Ketones Page 86 G. KMn 4 xidation of Aldehydes (aldehydes only) bserved Reaction H. Jones Reagent xidation of Aldehydes (aldehydes only) bserved Reaction This reaction prevents us from using Jones reagent to make aldehydes from 1 o alcohols. I. Tollens Reagent (oxidation of aldehydes) (aldehydes only) bserved Reaction This reaction was used as a chemical test for aldehydes (before IR/NMR). This test was called the silver mirror test. An aldehyde will be oxidized, and at the same time Ag + ions will be reduced to Ag o (silver metal). The Ag o deposits on the glass walls of the reaction container, forming a mirror. Formation of a mirror was considered a positive test, indicating that an aldehyde was present.