Aldehydes and Ketones: Nomenclature, Preparation, and Reactions, Study notes of Chemistry

Download Aldehydes and Ketones: Nomenclature, Preparation, and Reactions and more Study notes Chemistry in PDF only on Docsity! Aldehydes and Ketones Nomenclature - form text. The best way to think of an aldehyde or ketone (or just about any carbonyl compound) is with a slight positive charge on carbon, and a slight negative charge on oxygen: R O R' ! + ! - Just about all of the chemistry of carbonyl compounds is explained by the oxygen being slightly nucleophilic (thus easily protonated) and the carbon being strongly electrophilic. Remember this! Preparation: Aldehydes: 1) Oxidation of a primary alcohol with PCC 2) Ozonolysis of an alkene REVIEW IT! 3) Reduction of an Acyl Halide. Acyl halides can be reduced with a special reagent – lithium tri(t- butoxy)aluminum hydride, LiAl(Ot-Bu)3H : R O Cl OLiAl( )3H R O H Your text states that aldehydes can be easily prepared from esters with DIBAH (diisobutylaluminum hydride). Typically, it is easier to reduce all the way to a primary alcohol (you need 2 equivalents of DIBAH for this), then re-oxidize: R O OR' Al H (Diisobutyl aluminum hydride, or DIBAH, or DIBAL-H) R OH PCC R O H Ketones 1) Oxidation of secondary alcohols – usually be the Swern oxidation, or with PCC 2) Ozonolysis of an alkene. 3) Friedel-Crafts Acylation. Below is the preparation of a ketone sequentially from a primary alcohol (through an intermediate aldehyde): OH PCC O Li OH PCC O Some ketones can also be prepared from acyl halides and organo-copper reagents (called lithium dialkylcuprates), as shown below: Li CuBr Cu + LiBr Li CuLi 2 Lithium dialkylcuprate O R Cl O R Further oxidation of aldehydes and ketones: As you might imagine, most ketones are inert to all but the harshest oxidative conditions, and thus there is no synthetic utility in trying to oxidize them. However, aldehydes can generally be oxidized to carboxylic acids under relatively mild conditions: O R H Ag2O / H2O NH4OH / EtOH O R OH Reactivity of Aldehydes and Ketones. These carbonyl compounds generally have two reaction pathways – they react with strong nucleophiles (generally, strong nucleophiles have a formal negative charge) under neutral, generally anhydrous conditions, or with weak nucleophiles (those with lone pairs, but no charge) under mild acid catalysis. If you take a good look at the nucleophile and reaction conditions, you’ll be able to figure out which way it will go... Reactivity – aldehydes are much more reactive than ketones. ‘nuff said. Addition of water or alcohols (to from a hydrate or alcoholate (ketal)). Ketones and aldehydes in aqueous or alcoholic media frequently react with the medium to form hydrates (or alcoholates). The extent to which this occurs correlates to many things, including the electrophilicity of the carbonyl carbon. While acetophenone exists mostly as the ketone, trichloroacetaldehyde (chloral) exists almost entirely as the hydrate (if exposed to water): O H2O O HO OH Very little O H Cl Cl Cl H2O H Cl Cl Cl O H Cl Cl Cl HO OH Very little In the case of secondary amines, we have a lack of protons that can easily be removed from the amine – the mechanism thus requires that the offending positive charge be neutralized by removing a proton from the alkyl group: Overall: N HO N O O N H proton transfer HO N H O H H H2O N N H O H N H N No proton on amine to remove! -> remove proton from former ketone... H H De-Oxygenation reactions. There are two general reactions for the complete de-oxygenation of ketones and aldehydes. The general scheme for de-oxygenation is: O R R' R' can = H De-Oxygenate R R' The two methods are the Wolff-Kishner (runs under basic conditions) and the Clemmensen (under acidic conditions). Below find an example for each one: Wolff-Kishner: O H2NNH2 KOH HEAT! NNH2 Clemmensen: O Zn(Hg) HCl Heat The Greatest Double Bond Forming Reaction Ever Invented: The Wittig Reaction This reaction is what I would call “cute” chemistry. One of the cool thing about Wittig reactions is that they just about always work. The most general scheme, an alkyl halide (usually the bromide) and an aldehyde or ketone are taken to an alkene. If an aldehyde is used with a primary alkyl halide, generally the trans product results. R R' O Either R' or R'' MUST be hydrogen R'' R''' Br H + R' R R'' R''' In a more detailed picture of this reaction, the alkyl bromide is allowed to react with triphenyl phosphine to form an alkylphosphonium salt: R R' Br H PPh3 Ph PPh Ph R R' HBr These salts are generally quite stable, and can be stored over long periods of time (i.e. many of these salts are even sold commercially). The phosphonium salt is then deprotonated (usually with sodium hydride, or butyllithium) to form the ylide. An ylide is simply a charge-separated species, as shown below: Ph PPh Ph R R' HBr NaH Ph PPh Ph R R' "ylide" This ylide is then allowed to react with a ketone or aldehyde, to form a betaine intermediate. This intermediate cyclizes to form another intermediate, an oxaphosphetane: Ph3P R R' O R''' H Ph3P R R' R''' O H Ph3P R R' R''' O H betaine oxaphosphetane The oxaphosphetane decomposes rapidly to form the alkene and triphenylphosphine oxide: Ph3P R R' R''' O H H R'R R''' + Ph PPh Ph O The main driving force for this reaction is the formation of the phosphorous-oxygen double bond - this is one of the strongest bonds known, and its formation pulls the reaction to completion. Below are a few examples of the Wittig reaction at work: O Cl 1) PPh3 2) BuLi O PPh 3 O OTMS OTMS OTMS OTMS O H+ OH OH O OH OH PCC O O PBr3 Br Br PPh3 PPh 3Br PPh 3Br PPh 3 PPh 3 + NaH A simple modification of the Wittig reaction leads to a dibromo-olefin, which is an excellent precursor to alkynes: