Chemistry 318N Lecture 24: Amines and Nucleophilic Addition Reactions, Exams of Chemistry

Download Chemistry 318N Lecture 24: Amines and Nucleophilic Addition Reactions and more Exams Chemistry in PDF only on Docsity! 1 Chemistry 318N Lecture 24 April 17, 2008 Amines Chemistry 318N Important Stuff
Midterm Exam III – Wed April 23th – 7:00-9:00 PM Room WEL 1.308 Review
Mon 4/21 WEL2.122 at 7 PM
Tues, 4/22 Painter 3.02 at 7 PM
Please do a good job – Know the reactions (cards) – Review homework and the exams posted on the web – Practice synthesis and reactions – Know the Fischer Esterification mechanism – Malonic and acetoacetic ester syntheses and aldol – Covers material through today’s lecture 2 Chemistry 318N
1,2-addition (direct addition) –nucleophile attacks carbon of C=O (numbered 2)
1,4-addition (conjugate addition) –nucleophile attacks 4 or β-carbon Nucleophilic Addition to α,β-Unsaturated Aldehydes and Ketones C C C O 1 2 34 αβ Chemistry 318N Crazy Numbers and letters 4 3 2 1 IUPAC β α Trivial 4 3 2 Reaction Methyl vinyl ketone or 3-buten-2-one 1O 5 Chemistry 318N H Y+C C C O 1,2-addition C C C OH Y 1,4-addition C C C O HY C=O is stronger than C=C 498 121 O=O 614 134 C=C Chemistry 318N 4 1 1,4 addition gives the enol O Nu O Nu HOH OH Nu 6 Chemistry 318N After enol tautomerism 1,4 looks like 3,4!!?? 4 3 O OH Nu OH- HOH O Nu Chemistry 318N Some Bond Energies 83 178 146 83 111 99 ∆∆H ~ 20kJmol-1 7 Chemistry 318N
observed with strongly basic nucleophiles –Grignard reagents –LiAlH4 –NaBH4 –Sodium acetylide
strongly basic nucleophiles add 1,2 & irreversibly 1,2-Addition Chemistry 318N Example O CH3CH CHCH + HC CMgBr 1. THF 2. H3O+ OH CH3CH CHCHC CH 10 Chemistry 318N Gilman Reagents
Surprisingly, Gilman reagents undergo conjugate addition to α, β-unsaturated aldehydes and ketone O 1 . (CH 3 ) 2 CuLi, ether, - 78°C 2 . H 2 O, HCl O 3-Methyl-2- cyclohexenone 3,3-Dimethyl- cyclohexanone CH3 CH3 CH3 Chemistry 318N Gilman Reagents
Gilman reagents are unique among organometallic compounds in that they give almost exclusively 1,4- addition
Other organometallic compounds, including Grignard reagents, add to the carbonyl carbon by 1,2-addition
The mechanism of conjugate addition of Gilman reagents is not fully understood 11 Chemistry 318N Selectivity!! O RMgX HO R R2CuLi O R Chemistry 318N Michael Reaction
Michael reaction: the 1,4-addition of an enolate anion to an α,β-unsaturated carbonyl compound!!
Following are two examples – in the first, the nucleophile is the enolate anion of malonic ester – in the second, it is the enolate anion of acetoacetic ester 12 Chemistry 318N Michael Reaction + 3-Buten-2-one (Methyl vinyl ketone) Diethyl propanedioate (Diethyl malonate) O EtOC CH2 EtOC O O EtOC CHCH2 CH2 CCH3 EtOC O O O Et O- Na + EtOH CH2 =CHCCH 3 Chemistry 318N Michael Reaction + 2-Cyclohex- enone Ethyl 3-oxobutanoate (Ethyl acetoacetate) O O O O CH3 C CH2 EtOC O EtOC CH CH3 C O EtO - Na + EtOH 15 Chemistry 318N Robinson annelation: 2. aldol condensation OCH3 O O CH2CH2CCH3 NaOH heat OH O CH3 O not isolated; dehydrates under reaction conditions Chemistry 318N OCH3 O O CH2CH2CCH3 NaOH heat O O CH3 OH O CH3 O Robinson annelation: 3. elimination 16 Chemistry 318N The Signature Page Claisen Condensation: β-ketoesters Dieckmann: Cyclic β-ketoesters Aldol: α, β-unsaturated aldehydes and ketones Acetoacetic ester synthesis: decorated acetones Malonic ester synthesis: decorated acetic acids Michael Reaction: 1-5 dicarbonyl compounds Grignard Reaction: Alcohols…, etc. Chemistry 318N Make starting with ethyl acetate or diethyl malonate and anything else O O H HO O O Please work the problems on the posted exams! 17 Chemistry 318N Given ethyl alcohol as your only source of carbon, outline a synthesis to 3-ethylpentan-2-one Chemistry 318N Amines 20 Chemistry 318N
Amine Conj. Acid pKa
NH3 NH4 + 9.3
CH3CH2NH2 CH3CH2NH3 + 10.8
(CH3CH2)2NH (CH3CH2)2NH2 + 11.1
(CH3CH2)3N (CH3CH2)3NH + 10.8
C6H5NH2 C6H5NH3 + 4.6 Basicity of Amines in Aqueous Solution Chemistry 318N H2N •• Decreased basicity of arylamines +HN H H + NH2 + •• + H3N pKa = 4.6 pKa =10.6 Stronger acid Weaker acid Stronger base Weaker base 21 Chemistry 318N Decreased basicity of arylamines C6H5NH2 (C6H5)2NH (C6H5)3N pKa of conjugate acid: 4.6 0.8 ~-5
Increasing delocalization makes diphenylamine a weaker base than aniline, and triphenylamine a weaker base than diphenylamine. Chemistry 318N p-Nitroaniline NH2 O N O – •• •••• •• + •• •• O N O – •• •••• •• •••• – NH2 ++
Lone pair on amine nitrogen is conjugated with p- nitro group—more delocalized than in aniline itself. Delocalization lost on protonation. 22 Chemistry 318N Effect is Cumulative
Aniline is 3800 times more basic than p-nitroaniline.
Aniline is ~1,000,000,000 times more basic than 2,4-dinitroaniline.