Prerequisites: 333
Prerequisites: 333
CHEM 334
www.chem.sc.edu/faculty/bryson/index.html
Linked to course syllabus and “WEB PAGE”
synthesisModified from sides of William Tam & Phillis Chang
29/32
Due the second recitation: (1) Answer the following question in some detail.
(2) Complete review work sheet of 333 reactions.
What study activity (activities) helped you the most in CHEM 333?
Assignments
Text Solomons (10th ed)Schedule of tests and “projected” paceHonor codePolicy - grading scaleRecitation
WEB PAGE Homework problems, aids, etc
SYLLABUS“must read”
(linked to the “Home” and WEB Page*)
*www.chem.sc.edu/faculty/bryson/index.html
CHAPTER 12
Alcohols from Carbonyl Compounds Alcohols from Carbonyl Compounds Oxidation-ReductionOxidation-ReductionOrganometallic CompoundsOrganometallic CompoundsSrtucture of the carbonyl groupC=O addition/ROH oxidation
Hydrogenation of “double bonds”olefins and carbonyls
LiAlH4 NaBH4
Oxidation w/ PCCOxidation w/ H2CrO4 and KMnO4
Organometallic compounds R-Li & RMgX
Organometallics as basesOrganometallics as Nu:(-) with:
carbonylsepoxidesestersSynthesisChapter 12
Chapter 12
CHEM 334
Ch. 12 - 5
Structure
Carbonyl carbon: sp2 hybridizedPlanar structure
Ch. 12 - 4
Structure of the Carbonyl Group, Carbonyl compounds
aldehydealkanal
ketonealkanone
Others:
Y = OH, OR’, NH2, X, etc.
Ch. 12 - 6
RxsRxs of of Carbonyl Compounds Carbonyl Compounds with with NucleophilesNucleophiles
One of the most important reactions: nucleophilic addition to the carbonyl
recall:
Ch. 12 - 7
Two important nucleophiles (bases):
Two important reactions:
Hydrides (H:(-) from NaBH4 & LiAlH4 )Carbanions (from R:(-)(+)Li & R:(-)(++)Mg(-)X )
Ch. 12 - 8
Oxidation-Reduction Rxsreduction: increase in hydrogen content or decrease in oxygen
content
carboxylicacid
aldehyde
oxygen contentdecreases
hydrogen contentdecreases
oxidation: increase in oxygen content or decrease in hydrogen content
Ch. 12 - 17
Alcohols by Reduction of Carbonyl Compounds
Ch. 12 - 18
Alcohols by Reduction of Carbonyl Compounds
(1o alcohol)
Ch. 12 - 19
HydridesHydrides
Nucleophilic and very basicReact violently with H2O or protic sourcesRxs in Et2O or THF, reduces all carbonyl groups
LiAlH4 =
less reactive & less basic than LiAlH4
uses protic solvent (e.g. EtOH)reduces only aldehydes and ketones
““LAHLAH””
NaBH4
Ch. 12 - 23
Examples
skip ether ex
Ch. 12 - 21
Mechanism
(neutralize)
Ch. 12 - 22
Mechanism
Esters (carboxylic acids) are reduced to 1o alcohols
Ch. 12 - 24
3C.3C. Summary of LiAlHSummary of LiAlH44 and NaBH and NaBH44 Reactivity Reactivity
ease of reduction
reduced by NaBH4
reduced by LiAlH4
Ch. 12 - 25
Oxidation of Alcohols
Oxidation of Primary (1Oxidation of Primary (1oo) Alcohols) Alcohols
special CrO3
reagents
strongeroxidants
Ch. 12 - 26
Special CrO3 reagent = PCC Reagent
pyridinium chlorochromate
Ch. 12 - 27
PCC oxidation
1o
3o
2o
No Reaction
Ch. 12 - 28
Oxidation of 1Oxidation of 1oo Alcohols to Carboxylic Acids Alcohols to Carboxylic Acids
Jones reagent
Ch. 12 - 29
Oxidation: CrO3 + H2SO4 [or H2CrO4 ] [or KMnO4/HO(-)/Δ then H+/H2O]
Ch. 12 - 34
Organometallic Compounds
organometallic compounds contain carbon-metal bonds
Ch. 12 - 35
Preparation of Organolithium &Organomagnesium Compounds
Order of reactivity of RXRI > RBr > RCl
Ch. 12 - 36
Examples
Ch. 12 - 37
Rxs with Compounds Containing Acidic HydrogensRxs with Compounds Containing Acidic Hydrogens
Grignard reagents and organolithium compounds are very strong bases
Ch. 12 - 38
Examples as base
+ Mg2+ + Br−
As nucleophiles:
Ch. 12 - 39
React as nucleophiles with epoxides
Ch. 12 - 41
Rxs of Grignard & Organolithium ReagentsRxs of Grignard & Organolithium Reagentswith Carbonylswith Carbonyls
Ch. 12 - 44
examples
Ch. 12 - 45
Reaction with esters3o alcohol
Ch. 12 - 46
Mechanism
Ch. 12 - 49
Addition-Elimination
Ch. 12 - 50
Planning a Grignard [or RLi ] SynthesisPlanning a Grignard [or RLi ] Synthesis
Synthesis of
Ch. 12 - 51
Method 1Retrosynthetic analysis
Synthesis
Ch. 12 - 52
Method 2Retrosynthetic analysis
Synthesis
Ch. 12 - 53
Method 3Retrosynthetic analysis
Synthesis
Ch. 12 - 56
RMgX & RLi reagents cannot be prepared in the presence of the following groups because of reactions (acid-base or nucleophilic addition) :
Ch. 12 - 58
Sodium or Lithium Alkynides (acetylides)Sodium or Lithium Alkynides (acetylides)Preparation of lithium alkynides
Reaction with aldehydes or ketones
Ch. 12 - 59
Synthesis and Protecting Groups
Ch. 12 - 60
Retrosynthetic analysis
However
disconnection
Ch. 12 - 61
Need to “protect” the –OH group first
Ch. 12 - 62
Synthesis