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ch18 lecture 2 march 10

ch18 lecture 2 march 10 - 18.7 O R2CCR H 2 General Reaction...

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Unformatted text preview: 18.7 O R2CCR' + H 2 General Reaction O X 2 H+ R2CCR' + X HX X is Cl2, Br2, or I2. Substitution is specific for replacement of hydrogen. Catalyzed by acids. One of the products is an Example O + Cl 2 O H2O Cl + HCl (61-66%) Example O CH H + Br 2 O CHCl3 CH Br + HBr (80%) Notice that it is the proton on the carbon that is replaced, not the one on the carbonyl carbon. 18.8 Mechanism of Halogenation Experimental Facts specific for replacement of H at the carbon equal rates for chlorination, bromination, and iodination Interpretation in ketone; zero order in first order halogen no involvement of halogen until after the rate-determining step Mechanism of Halogenation Two stages: first stage is conversion of aldehyde or ketone to the corresponding enol; is ratedetermining second stage is reaction of enol with halogen; is faster than the first stage Mechanism of Halogenation O RCH2CR' slow RCH OH CR' X fast 2 O RCHCR' X enol Enol is key intermediate Mechanism of Halogenation Two stages: first stage is conversion of aldehyde or ketone to the corresponding enol; is rate-determining second stage is reaction of enol with halogen; is faster than the first stage examine second stage first Reaction of enol with Br2 OH OH R2C Br CR' R2C Br CR' + Br + Br carbocation is stabilized by electron release from oxygen + OH R2C Br CR' Loss of proton from oxygen completes the process H O R2C Br Br +O R2C Br Br H CR' CR' 18.9 The Haloform Reaction Under basic conditions, halogenation of a methyl ketone often leads to carbon-carbon bond cleavage. Such cleavage is called the haloform reaction because chloroform, bromoform, or iodoform is one of the products. Example O (CH3)3CCCH3 Br , NaOH, H2O O (CH3)3CCONa + H+ O (CH3)3CCOH (71-74%) 2 CHBr 3 The Haloform Reaction The haloform reaction is sometimes used as a method for preparing carboxylic acids, but works well only when a single enolate can form. O (CH3)3CCCH yes 3 O ArCCH yes 3 O RCH CCH no 2 3 Mechanism First stage is substitution of all available hydrogens by halogen O RCCH3 X , HO O 2 O RCCX X32, HO O RCCHX RCCH2X X , HO 2 Mechanism Formation of the trihalomethyl ketone is followed by its hydroxide-induced cleavage O HO + RC 3 CX RC O CX 3 HO O RC O + O HCX RC OH + CX 18.10 Stereochemical consequences of enolization O H H H H + 4D O 2 KOD, heat O D D D D + 4DOH Mechanism O H H H H + OD H H O H + HOD Mechanism O H H D H + OD H H O H D OD Stereochemical Consequences of Enolization H3O+ H H3C C CH3CH2 100% R H2O, HO O CC6H5 50% R 50% S 50% R 50% S Enol is achiral H H3C C CH3CH2 R O CC6H5 H3C C CH3CH2 OH CC6H5 Enol is achiral H3C H S C O CC6H5 50% CH3CH2 H H3C R C O 50% H3C C CH3CH2 OH CC6H5 CC6H5 CH3CH2 Results of Rate Studies H H3C C CH3CH2 O CC6H5 Equal rates for: racemization H-D exchange bromination iodination Enol is intermediate and its formation is rate-determining 18.11 Effects of Conjugation in , -Unsaturated Aldehydes and Ketones Relative Stability aldehydes and ketones that contain a carbon-carbon double bond are more stable when the double bond is conjugated with the carbonyl group than when it is not compounds of this type are referred to as , unsaturated aldehydes and ketones Relative Stability CH3CH CHCH2CCH3 O (17%) K = 4.8 O CH3CH2CH CHCCH3 (83%) Acrolein O H2C CHCH Acrolein O H2C CHCH Acrolein O H2C CHCH Acrolein O H2C CHCH Resonance Description C C C O C C O C+ +C C C O Properties , -Unsaturated aldehydes and ketones are more polar than simple aldehydes and ketones. , -Unsaturated aldehydes and ketones contain two possible sites for nucleophiles to attack carbonyl carbon -carbon C C C O Dipole Moments O + = 2.7 D Butanal O + = 3.7 D trans-2-Butenal greater separation of positive and negative charge + 18.12 Conjugate Addition to , -Unsaturated Carbonyl Compounds Nucleophilic Addition to , -Unsaturated Aldehydes and Ketones 1,2-addition (direct addition) nucleophile attacks carbon of C=O 1,4-addition (conjugate addition) nucleophile attacks -carbon Kinetic versus Thermodynamic Control attack is faster at C=O attack at -carbon gives the more stable product O C C C + H Y 1,2-addition H O C Y C C formed faster major product under conditions of kinetic control (i.e. when addition is not readily reversible) O C C C + H 1,4-addition Y enol goes to keto form under reaction conditions H O C Y C C O C C C + H 1,4-addition Y keto form is isolated product of 1,4-addition is more stable than 1,2-addition product O C Y C C H O C C C + H 1,4-addition Y 1,2-addition H O C Y C=O is stronger than C=C O C C C Y C C H 1,2-Addition observed with strongly basic nucleophiles Grignard reagents 4 LiAlH 4 Example O CH3CH CHCH + HC CMgBr 1. THF 2. H3O+ OH CH3CH CHCHC (84%) CH 1,4-Addition observed with weakly basic nucleophiles cyanide ion (CN ) thiolate ions (RS ) ammonia and amines azide ion (N ) Example O C6H5CH KCN CHCC6H5 ethanol, acetic acid via C6H5CH CN CH O CC6H5 O C6H5CHCH2CC6H5 CN (93-96%) C6H5CH CN CH O CC6H5 Example O via O CH3 CH3 C6H5CH2SH HO, H2O O SCH2C6H5 O CH3 (58%) SCH2C6H5 CH3 SCH2C6H5 18.13 Addition of Carbanions to , -Unsaturated Carbonyl Compounds: The Michael Reaction Michael Addition Stabilized carbanions, such as those derived from -diketones undergo conjugate addition to , -unsaturated ketones. Example O CH3 + O HC 2 O CHCCH 3 KOH, methanol O CH3 O CH CH CCH O 2 2 3 (85%) Michael Addition The Michael reaction is a useful method for forming carbon-carbon bonds. It is also useful in that the product of the reaction can undergo an intramolecular aldol condensation to form a six-membered ring. One such application is called the Robinson annulation. Example O CH3 O O CH3 CH2CH2CCH3 O NaOH heat O OH O CH3 not isolated; dehydrates under reaction conditions (85%) O 18.14 Addition of Organocopper Reagents to , -Unsaturated Aldehydes and Ketones The main use of organocopper reagents is to form carbon-carbon bonds by conjugate addition to , -unsaturated ketones. O + LiCu(CH )2 CH3 3 Example 1. diethyl ether 2. H2O O CH CH3 3 (98%) ...
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