CH 19: Aldehydes and Ketones

Transcription

1 rganic hemistry otes by Jim Maxka 19: Aldehydes and Ketones Topics aming, structure, and properties Formation of = eactions with weak nucleophiles: and Derivatives: imines and enamines. eactions with strong nucleophiles Wittig onjugate Addition Protection M and I onnections: 2 ways reductive wkup oxidatvie wkup and and l 1 or

2 rganic hemistry otes by Jim Maxka Aldehydes and Ketones aming: Some general rules: 1. In general, the most oxidized gets the highest priority (lowest #) but terminal (on the end) takes precedence. 2. When more than one functional group is present, the # of the highest priority group goes in the middle of the molecule. heckup: Which takes higher priority? Alkenes or alcohols? Aldehydes or alcohols? Draw 2-propen-1-ol Draw 2,3,4-trihydroxybutanal (common name?) Ketones or alcohols? Ketones or aldehydes? ow to name: The naming convention for aldehydes is the IUPA alkane e al. The aldehyde based on one carbon goes methane e = methan al = methanal; ethane e = ethan al = ethanal. Draw propanal: Draw cyclohexanal: The common names for aldehyde is the common root aldehyde. The common root for one carbon is form, the aldehyde is formaldehyde. The common name for two carbons is acet, the name is acetaldehyde. The simplest aromatic is based on benz, benzaldhyde. Pet name for aldehydes and ketones: ommon roots structures Form Acet * Benz 3 * * Draw formaldehyde: Draw acetaldehyde: Draw benzaldehyde: When the aldehyde cannot be named in the longest chain or ring it is referred to as carbaldehyde. ow draw cyclohexanecarbaldehyde. Ketones occur internally in a molecule, because the carbonyl must be substituted by on both sides. The simplest ketone is based on three carbons. The IUPA name is propane e = propan one = propanone. Draw propanone ow does acetone have the acet root? 19-2

3 rganic hemistry otes by Jim Maxka ommon names are based on substituents on both sides of the = (like ethers). Draw and name the IUPA and common name on the ketone made up of 4 s. Pentanone has two isomers, the = in position 2 or 3, called 2-pentanone and 3-pentanone respectively. Draw them. ow test yourself on these examples: What would acetophenone look like? When a ketone is not the highest priority, it is called oxo because it looks like an oxygen substituent hanging off the molecule. What functional groups take priority over ketone? *****Synthesis of aldehydes and ketones****** A. xidation eactions involving adehydes and ketones: xidation is the gain of bonds loss of bonds to. eduction is the gain of bonds loss of bonds to. Take the metabolic path of ethanol 3 2 [] 3 [] 3 1 Bond ==> 2 Bonds ==> 3 Bonds ==> In the lab, there are 3 pathways and 3 reagents to learn: 2 From alcohol carboxylic acid, (2 steps in one) use Jones eagent (r 3 2 S 4 ) From alcohol aldehyde, (only one step) use P (pyridnium chloro chromate = Pyridine l r 3 ) From aldehyde carboxylic acid, (one step) use Ag 2. In the above oxidations, what is the fate of the metals? r 3 goes from oxidation state= to r 2, oxidation state=. Ag 2 goes from oxidation state= to Ag(s), oxidation state=. In both cases, we say that the metal was. 19-3

4 rganic hemistry otes by Jim Maxka B. Formation of enols: Another way to make aldehydes via unstable alcohols is to react terminal alkynes with B 3 /basic peroxide solution. eact 1-butyne with these reactions. What is the final process? 1. B 3 /TF Keto-enol tautomerism /hydroxide 3. zonolysis followd by reductive workup: Aldehydes can also be produced from alkenes with 3 and reducing workup. What reagents are used? For practice take 1-butene and make formaldehyde and propanal w/reducing workup; propanoic acid and 2 water with oxidizing workup. red workup intermediate ox workup Ketones A. xidation of alcohols: Ketones are prepared by oxidation of alcohols, in which an can be lost. eagents such as Jones or P work fine. Which alcohol would you use to make methyl ethyl ketone? B. Formation of enols: Alkynes are hydrated with acidic aqueous solution with mercury catalysts to give a ketone upon keto-enol tautomerization. Take 2-butyne with the hydrating reagents above 2, gl 2, l Keto-enol tautomerism zonolysis followed by oxidative workup Ketones can be produced by ozonolysis or directly with KMn methyl-2-butene? intermediate Zn/l acetaldehyde acetone What is this type of reaction called? 2-methyl-2-butene? intermediate KMn 4 acetone acetic acid reaction called? What is this type of Practice: Predict the products of the ozonolysis of 1-butene with both oxidizing or reducing workup.. What alkenes would these ozonolysis products come from and under what conditions? 2 = =( 3 ) 2 ( 3 ) 2 = 2 and water 19-4

5 rganic hemistry otes by Jim Maxka D. Freidel rafts Acylation. Aryl ketones can be made by Friedel-rafts acylation. What reagents would make acetophenone from benzene? E. Gilman reagents with acyl halides: Finally, ketones can be made by substitution of the l in an acyl chloride, by 2 u - Li (called the Gillman reagent). Which Gillman reagent and acyl chloride would you use to make acetone? Acetophenone? eview of rganometallic reagents? ompare all the familiar organometallic reagents: (a) Grignard (b) Alkyl Li reagents (c) Gillman reagent What functional groups do these reagents react with? The Gillman reagents do not react with To make a Grignard: -Br Mg/Et 2 MgBr To make an alkyl Li reagent: -Br 2Li -Li LiBr To make a Gillman reagent: 2 -Li u(i)l 2 u - Li Lil *************Aldehyde and Ketone eactions 1************ ne of the main reactions of the carbonyl is based on its dipolar structure, as shown in the resonance structure below: This form show the positive charge on, and more reactive towards. This form will explain more than half of all carbonyl reactions. There are two ways to look at this reaction. ne is for the strong nucleophile, for example. Strong nucleophiles have concentrated negative charge or the lone pair on :. Strong nucleophiles are also. So, these solutions are often basic. For weak nucleophiles, for example, there is a lone pair but not concentrated negative charge. Weak nucleophiles need help to react with the carbonyl. This is done by protonating the = with an catalyst as shown below. 19-5

6 rganic hemistry otes by Jim Maxka xonium arbo cation Which resonance contributor is the bigger contributor? Why? Let s look at adding water to the =. First under acid conditions: regeneration of the catalyst otice: (1) The circled is the catalyst regenerated at the end of the reaction. (2) What is the hybridization of the in the third structure? (3) The product is a gem-diol, that is two alcohols on the same. Is that oxidized or reduced? (4) The entire reaction is in. That means that the reaction could go either way. In fact, the reaction is not a very good one except for formaldehyde and 1 =l 3, 2 =. The name of the products are formaldehyde hydrate and Knock out drops, respectively. For all ketones, the equilibrium lies far to the left. Why? (1) Steric: (2) Electronic nly weak acid is effective for the catalysis of the hydrate reaction. What is the problem of performing the reaction in strong acid: Base ydration of formaldehyde: - ow many moles of water are consumed in this reaction? The acid catalyzed reaction? Why would the reaction not work if the solution were strongly basic? Acetal and emiacetal formation: ext the reactions of alcohols leads first to an alcohol ether and then to two ethers. The name of the first is hemiketal (from ketone) or hemiacetal (from aldehyde); the fully substituted compound is called ketal or acetal. 19-6

7 rganic hemistry otes by Jim Maxka ow for the hemiacetal mechanism in dilute acid: regeneration of the catalyst The hemiacetal is an alcohol-ether. Is the oxidized or reduced? ow to finish with the full acetal: 3 3 Good LG The 2 2 regeneration of the catalyst Application Sugars exist in cyclic and linear forms. Glucose, a common sugar, is actually an aldehyde. Below is the glucose equilibrium. 2 The only difference between the two cylic forms are that one has the new axial and one has the new equatorial. Which functional group is formed when glucose cyclizes? Is this reaction easily reversible? Why? When two or more glucose molecules condense leading to a loss of water, we get a polymer. This form is called cellulose when the equatorial bonds lose water and form these ether linkages. What is the functional group formed here? ellulose is the form, assembled to make plant fiber. bviously, cellulose is a stable material. Why is cellulose not reversible with the aldehyde? 19-7

8 rganic hemistry otes by Jim Maxka ************Aldehyde and Ketone eactions 2************ ow for nucleophiles. 1 o amines react with ketones and aldehydes to make = or imines: You supply arrows and draw the product S: - S 3 S 2 S acidic 3 3 S 3 S immonium ion The product is called an imine. Imine is = This reaction works because there is an acidic proton on the to lose, which is eventually transferred to. When there is no to lose on the, the proton must come from next to the =, this is called the enamine. The enamine comes from the reaction of a 2 0 amine. We pick up the mechanism at the elimination of water S: 2 S Pepping up the reaction: It turns out that 1 o and 2 o amines are not very reactive. If we want to make the reaction go better, we have to strengthen the nucleophile. What type of group would you put next to the amine to make the reaction stronger? EDG- 2 or EWG- 2? ere are some examples: = 2 hydroxyl amine 2 2 hydrazine 2 hydrazine derivatives = * 2 semi-carbazide 2 2 * 2, 4-dinitrophenyl There are 2 types of reactions. ne is to make derivatives, that is to turn an liquid aldehyde or ketone into a solid. This was done for identification purposes in the past, but still has usefulness for separations. Derivatization involves reaction with either hydroxyl amine or one of the hydrazine derivatives to make the imine product. All follow this reaction scheme shown next. 19-8

9 rganic hemistry otes by Jim Maxka 2-2 S: - S S 2 S derivative acidic S S immonium ion You should be aware of these 3 types of. (1) - 2 called hydroxylamine leading to an oxime. (2) 2 = 2 called a semicarbazide leading to a semicarbazone. 2 2 (3) 2 called 2,4-dinitrophenyl hydrazine leading to a hydrazone. All of these compounds are crystalline. ******************************************** 2 nd type of reaction is the reaction of hydrazine, 2 2, alone is important because if performed at high temperatures in strong base, it leads to reduction of the = to 2. Wolff-Kishner (g) Is this process oxidation or reduction? A similar reaction but performed under acidic conditions is the lemenson reduction. We have seen this type of reduction in ozonolysis and in reduction of nitroaromatics. The reagent is Zn(g) and aqueous acid. Metals that dissolve in one another to form a new metal are called an amalgam. The product is the same as the Wolff-Kishner: Benzaldehyde l Zn(g) Toluene 2-cyclohexenone would T react cleanly with lemmenson. What would be the problem? ow would you reduce the =? 19-9

10 rganic hemistry otes by Jim Maxka ecap Aldehydes and Ketones react with weak nucleophiles under acidic or basic catalytic conditions like this u :u u u In short, aldehyde/ketone nucleophile aldehyde/ketone u: 3 u 2 To push the reaction to right, add u or remove water; to push the reaction to left react in aqueous acid. otter ucleophiles: (remember what makes really good nucleophiles) (1) Grignard reagents: MgBr = : - MgBr Think of the as a carbanion. What is the product of MeMgBr methyl ethyl ketone followed by acid workup? 1. MeMgBr acid workup (2) ydride, : - is a very strong nucleophile found in LA and ab 4. Think of LA = Al 3 Li : - What about ab 4? 1. LA acid workup (3) Finally, we need to look at : -, cyanide, a natural poison: and a synthon, because can be turned into amine or acid. The product is called a cyanohydrin: :- - :- acid hydrolysis LA

11 rganic hemistry otes by Jim Maxka Wittig eaction: Formally, the Wittig reaction is the exchange of the in =, for the 2 in P= 2. Ph 3 P Ph 3 P= Ketone Wittig eagent Alkene phosphine oxide There are several key steps to this reaction: Step 1 Formation of the Wittig eagent: S 2 eaction of Ph 3 P: with an alkyl halide followed by removal of by strong base. Ph 3 P: 2 B r Ph 3 P 2 What is the strong base used here? What happens to the strong base after it takes a proton? removed from the reaction? Step 2: eaction of the Wittig with the =: Br Bu Li Ph 3 P 2 Ph 3 P Does it have to be Ph 3 P 2 Ylide form PPh 3 Betaine PPh 3 Ph 3 P= Which combination of ylide and ketone would make the following alkenes? Each has two ways. Which is better? 6 5 = 2 (styrene) ( 3 ) 2 = 2 Summary of Wittig. Formally, the Wittig replaces the in the = with the in the Wittig reagent, Ph 3 P= 2. The Wittig reagent is written in many forms. The Ph 3 P= 2 ; the ylide form, Ph 3 P ; and the ingredients form: (1) Ph 3 P -Br, (2) BuLi, (3) Add to =. onjugate Addition: When a carbonyl is conjugated with an alkene, it is called an alpha-beta unsaturated carbonyl compound. This alkene is activated and can be attacked by a nucleophile. This process is called conjugate addition, because the double bond is u u u u The product is a ketone substituted on the Beta carbon by a nucleophile. Suitable nucleophiles are (1) amines or (2) alkyl uli reagents = 2 uli. What other reaction do we know for 2 uli? Give an example: 19-11

12 rganic hemistry otes by Jim Maxka rganouli reagents are different than Grignards. What are the products of 3-buten-2-one with MeMgBr or Me 2 uli followed by acid workup? 2 3 but-3-en-2-one 1. MeMgBr 2. acid workup 1. Me 2 uli 2. acid workup Protection of Ketones and Aldehydes Some reactions require protection to selectively block one group from reaction: We can protect two functional groups: and The method is different: For -, we need to block what? We do this by adding TMS-l [( 3 ) 3 Si-l] to the alcohol and pulling off the with a non-nucleophilic base. A typical sequence goes like this: TMS-l pyridine MeMgBr TMS Et TMS acid workup F- The sequence is always: 1. Protection 2. eaction 3. Deprotection What would be the result of the reaction if the alcohol were not protected? We can also protect aldehydes and ketones (usually to differentiate carboxylic acids and esters.). We do this by pushing the hemiacetal equilibrium by adding excess alcohol and a diol to favor intramolecular acetal formation. bviously, the acetal does not react like the ketone. ethylene glycol, - 2 LA 3 excess 3 3 Et 2 xs acid workup What is involved in the deprotection reaction? What would be the product of LA reduction without deprotection? Write out the equilibrium between the ketone and the ketal and be sure you understand how it works. This is a very important concept

13 rganic hemistry otes by Jim Maxka M and I of arbonyls I: =: Prominent peak near 1700 cm -1 and note the aldehyde peak. 1 M: Ketones and aldehydes have allylic 1 on the alpha. Where does the 1 peak for acetone resonate? The aldehyde 1 resonates between 9-10 ppm. This is because it is on a that is highly

14 rganic hemistry otes by Jim Maxka 13 M: 13 M is like proton M. There are regions for each type of. nly the numbers are a little different 1 goes from 0-10ppm, 13 goes from 0-200ppm: Saturated 0-40, allylic 40-60, -E: 60-80, vinyl , aromatic and a bonus of the 13 is the 13 =: This one comes near 200ppm

15 rganic hemistry otes by Jim Maxka The only way to distinguish acetone from hexamethylbenzene is with 13 M. What would the 1 M look like? ere are the 13 M spectra: 19-15

16 rganic hemistry otes by Jim Maxka Practice: Find the structure for the molecules below given these 13 M spectra, all have the formula 4 8 : The 1 M shows a peak at 9.6 ppm. o 1 M peaks over 3 ppm for the compound below. Mass Spec leavage at the alpha :

17 rganic hemistry otes by Jim Maxka