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