aldehydes-ketones.pdf

Aldehydes and Ketones: Nucleophilic Addition Reactions CHEM 245 AE 1  Aldehydes and Ketones Aldehydes and ketones are characterized by the carbonyl functional group (C=O) O Carbonyl oxygen C Carbonyl carbon The c...

Aldehydes and Ketones: Nucleophilic Addition Reactions CHEM 245 AE 1  Aldehydes and Ketones Aldehydes and ketones are characterized by the carbonyl functional group (C=O) O Carbonyl oxygen C Carbonyl carbon The carbonyl group The compounds occur widely in nature as intermediates in metabolism and biosynthesis They are also common as chemicals, as solvents, monomers, adhesives, agrichemicals and pharmaceuticals CHEM 245 AE 2 Naming Aldehydes and Ketones Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al The parent chain must contain the CHO group ◦ The CHO carbon is numbered as C1 If the CHO group is attached to a ring, use the suffix See Table 19.1 for common names CHEM 245 AE 3 Naming Ketones Replace the terminal -e of the alkane name with –one Parent chain is the longest one that contains the ketone group ◦ Numbering begins at the end nearer the carbonyl carbon CHEM 245 AE 4 Aldehydes have the general formula. O R C H or RCHO (R = H or C) Aldehyde function IUPAC system Aliphatic aldehydes are named by dropping the suffix -e from the name of the hydrocarbon that has the same carbon skeleton as the aldehyde and replacing it with the suffix -al. Alkane - e+ al = Alkanal O O O O C H H H3C C H H3CH2C C H H3CH2CH2C C H Common name: Formaldehyde Acetaldehyde Propionaldehyde Butyraldehyde IUPAC name: Methanal Ethanal Propanal Butanal Alkenal in case of double bond, Alkynal in case of triple bond CHEM 245 AE 5 Ketones: Structure Ketones have the general formula. O R C R' (R and R' = alkyl or aryl) The carbonyl group may appear at any of various positions in the chain, except at the end. The R groups need not be the same; either or both may be aliphatic or aromatic. O O O O H3C C CH3 H3C C CH2CH3 H3C C C6H5 C6H5 C C6H5 In ketones the carbonyl group may also be part of a cyclic structure. O By listing the alkyl substituents attached to the carbonyl group, followed by the word ketone. CHEM 245 AE 6 The simplest alphatic ketone, dimethyl ketone, is usually called acetone. When the carbonyl group of a ketone is attached to a benzene ring, the ketone may be similarly named, or it may be given a special name. In the IUPAC system, ketones named in the usual manner. The longest continuous chain carrying the carbonyl group. Name the parent structure by dropping the suffix –e, lowest possible number to the C=O group. CHEM 245 AE 7 Substituted ketones are named by numbering and listing the substituents alphabetically. For cyclic ketones, numbering always starts from the C=O group. CHEM 245 AE 8 Ketones with Common Names IUPAC retains well-used but unsystematic names for a few ketones CHEM 245 AE 9 Ketones and Aldehydes as Substituents The R–C=O as a substituent is an acyl group is used with the suffix -yl from the root of the carboxylic acid ◦ CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain CHEM 245 AE 10 Physical Properties of Aldehydes and Ketones Boiling Points  Because of the polarity of the carbonyl group, Aldehydes and ketones are polar compounds.  The polar character of the molecules gives rise to intermolecular attractions.  These attractive forces, called dipole-dipole attractions. occur between the partial negative charge on the carbonyl oxygen of one molecule and the partial positive charge on the carbonyl carbon of another molecule.  Dipole-dipole attractions, although important, are not as strong as interactions due to hydrogen bonding. CHEM 245 AE 11  So the boiling points of aldehydes and ketones are higher than those of nonpolar alkanes, of comparable molecular weights. lower than those of alcohols, of comparable molecular weights. Solubility in Water. The lower aldehydes and ketones are soluble in water. Because aldehydes and ketones form hydrogen bonds with water.  As the hydrocarbon portion of the molecule increases, the solubility in water decreases rapidly.  Aldehydes and ketones with more than six carbons are essentially insoluble in water. CHEM 245 AE 12  Preparation of Aldehydes and Ketones Preparing Aldehydes Oxidize primary alcohols using pyridinium chlorochromate Reduce an ester with diisobutylaluminum hydride (DIBAH), LiAlH4, or NaBH4 CHEM 245 AE 13 Preparation of Aldehydes and Ketones Oxidation of Primary and Secondary Alcohols  Oxidation of primary alcohols, under controlled conditions, yields aldehydes. O [O] RCH2OH R C H 1o alcohol Aldehyde Oxidation of secondary alcohols yields ketones. O [O] R2CHOH R C R 2o alcohol Ketone  Aldehydes are very easily oxidized to carboxylic acids. O O H2Cr2O7 R C H R C OH Aldehyde Carboxylic acid CHEM 245 AE 14  Ketones from Ozonolysis Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted CHEM 245 AE 15 Aryl Ketones by Acylation Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst O O AlCl3 + H3CH2C C Cl C CH2CH3 Propionyl chloride Ethyl phenyl ketone (Prpiophenone) O O AlCl3 + C Cl C Benzoyl chloride Diphenyl ketone (Benzophenone) CHEM 245 AE 16 Methyl Ketones by Hydrating Alkynes Hydration of terminal alkynes in the presence of Hg2+ (ALKYNE SECTION) CHEM 245 AE 17  REACTIONS OF ALDEHYDES AND KETONES CHEM 245 AE 18  Oxidation of Aldehydes and Ketones CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids efficiently Silver oxide, Ag2O, in aqueous ammonia (Tollens’ reagent) oxidizes aldehydes (no acid) CHEM 245 AE 19 Hydration of Aldehydes Aldehyde oxidations occur through 1,1-diols (“hydrates”) Reversible addition of water to the carbonyl group Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols CHEM 245 AE 20 Nucleophilic Addition Reactions of Aldehydes and Ketones Nucleophific addition reactions to the carbon-oxygen double bond. In nucleophilic addition reactions The partially positive carbonyl carbon undergoes attack by electron-rich reagents, or nucleophiles (Nu:). The partially negative carbonyl oxygen is attacked by electron- deficient reagents, or electrophiles (E+). Addition of Metal Hydrides: Formation of Alcohols  Aldehydes can be reduced to primary alcohols.  Ketones can be reduced to secondary alcohols.  The initial addition product, after being hydrolyzed, yields an alcohol. CHEM 245 AE 21 Nucleophilic Addition Reactions of Aldehydes and Ketones Nu- approaches 45° to the plane of C=O and adds to C A tetrahedral alkoxide ion intermediate is produced CHEM 245 AE 22 Nucleophiles Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site The overall charge on the nucleophilic species is not considered CHEM 245 AE 23 Imine Derivatives Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines For example, hydroxylamine forms oximes and 2,4- dinitrophenylhydrazine readily forms 2,4- dinitrophenylhydrazones ◦ These are usually solids and help in characterizing liquid ketones or aldehydes by melting points CHEM 245 AE 24  Relative Reactivity of Aldehydes and Ketones Aldehydes are generally more reactive than ketones in nucleophilic addition reactions The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b) Aldehydes have one large substituent bonded to the C=O: ketones have two CHEM 245 AE 25  Electrophilicity of Aldehydes and Ketones Aldehyde C=O is more polarized than ketone C=O As in carbocations, more alkyl groups stabilize + character Ketone has more alkyl groups, stabilizing the C=O carbon inductively CHEM 245 AE 26 Reactivity of Aromatic Aldehydes Less reactive in nucleophilic addition reactions than aliphatic aldehydes Electron-donating resonance effect of aromatic ring makes C=O less reactive electrophilic than the carbonyl group of an aliphatic aldehyde CHEM 245 AE 27  Sodium borohydride, NaBH4, has the advantage of selectively reducing the carbonyl group of non-conjugated unsaturated aldehydes or ketones. Addition of Grignard Reagents: Formation of Alcohols Addition of Grignard reagents, R-Mg+X, to the carbonyl group is used for synthesizing all kinds of alcohols. The addition product, after it is formed, is hydrolyzed with aqueous acid to give an alcohol. It is possible to prepare 1°, 2°, or 3° alcohols, depending on what kind of carbonyl compound undergoes the addition reaction. CHEM 245 AE 28 Addition of Hydrogen Cyanide: Formation of Cyanohydrins  The addition is catalyzed by cyanide ion (good nucleophile).  Example CHEM 245 AE 29  Addition of Alcohols: Formation of Hemiacetals and Acetals A. Hemiacetals (and Hemiketals) Water and alcohols (weak nucleophiles), can add to the carbonyl group of aldehydes and ketones. An acid catalyst is required to speed the rate of reaction. The same as in alcohol The addition of one mole of an alcohol to the carbonyl group of an aldehyde yields a hemiacetal. CHEM 245 AE 30  The addition of one mole of an alcohol to a ketone gives a hemiketal. Hemiacetals and hemiketals have an alkoxy group (OR) and a hydroxy group (OH) attached to the same carbon. CHEM 245 AE 31 Step 1. Protonation of the carbonyl oxygen: O OH OH H+ H3C C H H3C C H H3C C H Step 2. The positively charged carbon is attacked by the weak nucleophile methanol. OH OH CH3OH + H3C C H H3C C O CH3 H H Step 3. The loss of a proton regenerates the acid catalyst and forms the hemiacetal. OH OH + H3C C O CH3 H3C C O CH3 + H H H H CHEM 245 AE 32 B. Acetals When hemiacetals are treated with an additional mole of alcohol in the presence of anhydrous acid, they are converted to Acetals.  Acetals have two alkoxy groups (OR) on the same carbon.  Acetals are stable compounds.  Acetals, like ethers, do not react with bases, oxidizing agents and reducing agents. CHEM 245 AE 33  Addition of Ammonia and Ammonia Derivatives  The addition of nitrogen nucleophile, such as ammonia(NH3) and substituted ammonia (NH2-Y). H+ C O + H2N-Y C N-Y + H2O Nitrogen nucleophile Nitrogen derivative of carbonyl compound NH3 C N H Ammonia Imine (mostly unsatble) NH2OH C N OH Hydroxylamine Oxime NH2 NH2 C N NH2 Hydrazine Hydrazone C O C N NH NH2 NH Phenylhydrazone Phenylhydrazine O2N O2N NH2 NH NO2 C N NH NO2 2,4-Dinitrophenylhydrazine 2,4-Dinitrophenylhydrazone O O H H NH2 N C NH2 C N N C NH2 Semicarbazide Semicarbazone CHEM 245 AE 34  Aldol Condensation Aldehydes and ketones have -hydrogens (slightly acidic) in presence of Alkali such as NaOH undergo condensation reaction. Base first abstract the hydrogen from the more acidic one and then it acting as Nucleophiles, which add to the carbonyl group of aldehydes and ketones, a larger organic molecule is formed with loss of water. CHEM 245 AE 35  Example Addition of enolate anion derived from acetaldehyde to the C=O bond of a nonionized acetaldehyde molecule. Step 1. When acetaldehyde is treated with dilute sodium hydroxide, A small but significant number of molecules are converted to the enolate anion. Ha HO H C C O H C C O H C C O + H2O H H H H H H Acetaldehyde Enolate (nucleophile) Step 2. The enolate anion, acting as a nucleophile, adds to the C=O bond of a nonionized acetaldehyde molecule left in solution to give an adduct that carries a negative charge on the oxygen. The adduct contains a newly formed carbon-carbon bond. CH3 O CH3 O O C CH2 C H O C CH2 C H H H CHEM 245 AE 36 Step 3. The negatively charged oxygen abstracts a proton from water. to give the final product, 3-hydroxybutanal, commonly known as aldol. CH3 O CH3 O O C CH2 C H + H2O HO C CH2 C H + OH- H H 3-Hydroxybutanal (Aldol)  The term aldol is derived from the combination of the words aldehyde and alcohol. The two functional groups present in the product.  The net overall reaction may be written as O b a O H 2 H3C C H + dil OH- H3C C CH2 C H OH Acetaldehyde Aldol (3-Hydroxybutanal)  The general overall reaction may be written as O O H O b a R'H2C C H + RH2C C H R'H2C C HC C H An aldehyde OH R Aldol CHEM 245 AE (B-Hydroxy aldehyde) 37  Crossed Aldol Condensation  Ifwe subject a mixture of two different aldehydes, each containing a hydrogen, to the aldol condensation, For example If acetaldehyde is added slowly to an excess of benzaldehyde in the presence of dilute sodium hydroxide, CHEM 245 AE 38  The Cannizzaro Reaction The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation) It considered as oxidation-reduction reaction CHEM 245 AE 39  Summary Aldehydes are from oxidative cleavage of alkenes, oxidation of 1° alcohols, or partial reduction of esters Ketones are from oxidative cleavage of alkenes, oxidation of 2° alcohols, or by addition of diorganocopper reagents to acid chlorides. Aldehydes and ketones are reduced to yield 1° and 2° alcohols , respectively Grignard reagents also gives alcohols Addition of HCN yields cyanohydrins 1° amines add to form imines, and 2° amines yield enamines Reaction of an aldehyde or ketone with Hydrazines form hydrazones Reaction of an aldehyde or ketone with Hydroxyamine forms oximes Alcohols add to yield acetals Reaction of aldehydres and ketones have alpha-hydrogen in presence of alkali undergo ALDOL REACTION (CODENSATION REACTION) Aldehydes or Ketone with no alpha-hydrogen in presence of Base undergo CANNIZARRO’s REACTION (OXIDATION-REDUCTION) CHEM 245 AE 40