Organic Chemistry Chapter 10

Functional Groups

The Key To Substitution Reactions The Leaving Group Goes

Substitution Rx of R-OH Alcohols have polar groups which make substitution probable Alcohols have a strongly basic leaving group (OH - ) which make it not probable Protonation converts an alcohol to a good leaving group

Mechanisms Wow… we get to draw one…….. From yahoo images

Substitution Rx of R-OH HBr and HI work well for S N 2 reactions. HCl does not work well because Cl is a poorer nucleophile. Rate can be increased using ZnCl 2 –Zn 2+ is a Lewis Acid –Complexes with the O: (this weakens the C-O bond)

Lucas Test.

Rearramgement OH ya, don’t forget -

“Grain” and “Wood Alcohol”.

Conversion of Alcohols Use phosphorous trihalides or thionyl chloride –Better yields and no rearrangements –PCl 3, PBr 3, PI 3, or SOCl 2 Do the Mechanism…………………….. From yahoo images

Conversion of Alcohols Pyridine is used as the solvent because it prevents formation of HCl or HBr and is a poor nucleophile.

Conversion of Alcohols Commonly Used Methods for Converting Alcohols into Alkyl Halides –ROH + HBrRBr –ROH + HIRI –ROH + HClRCl –ROH + PBr 3 RBr –ROH + PCl 3 RCl –ROH + SOCl 2 RCl    pyridine

Sulfonate esters leaving groups Conversion of alcohols to sulfonyl chlorides –p-toluenesulfonyl chloride (tosyl chloride, TsCl) –methylsulfonyl chloride (mesyl chloride, MsCl) –trifluoromethanesulfonyl chloride (trif) They are up to 100 x better than Cl - as leaving groups

Sulfonic acid has a pKa of – 6.5 wow!! That ought to be on stable base now don’t ya think?

Reaction steps

Dehydration of Alcohols Zaitsev’s Rule – more substituted formed

Dehydration of Alcohols Dehydration is the reverse of Hydration –vary conditions to control equilibrium –Remove the alkene by distillation

Dehydration of Alcohols Reaction may involve rearrangement

Dehydration of Alcohols rearrangements with ring opening

Dehydration of Alcohols E and Z produced, major product will have most bulky groups on opposite sides

Dehydration with POCl 3 Uses a better leaving group Conditions are not as extreme Phosphorous oxychloride and pyridine No rearrangements Mildly basic conditions favor E2

Oxidation of Alcohols From yahoo images Look at reaction and conditions For Primary and Secondary Alcohols

Substitution Rx of Ethers Ethers can be activated by acid High concentration of HI, HBr will form the alkyl halide

Ethers are relatively unreactive so they are frequently used as solvents –diethyl ether (ether) –tetrahydrofuran (THF) –1,4-dioxane –1,2-dimethoxyethane (DME) –methyl t-butyl ether (MTBE) Ethers as Solvents

Addition of Peroxyacids Alkenes can be oxidized to an epoxide by a peroxyacid.

Reactions of Epoxides Because of 3 membered ring, epoxides are much more reactive than normal ethers Undergo ring opening reactions at room temp

Reactions of Epoxides (oxiranes) Formation of glycols (addition of H 2 O)

Reactions of Epoxides (oxiranes)) Unsymmetrical additions yield the product resulting from Nu: attack on the more substituted carbon

Reactions of Epoxides (oxiranes) Under basic conditions, Nu: attack is at the less hindered C The epoxide is reactive enough that you don’t need to protinate to get the reaction to go

Crown Ethers

Cyclic compounds with ether linkages Bind cations as “host” and “guest”

Crown Ethers Naming – [x]-crown-Y X = total number of atoms in the ring Y = total number of oxygens

Thiols and Sulfides

Thiols are sulfur analogs of alcohols Also called mercaptans (mercury capturing)

Thiols and Sulfides Thiols are named by adding suffix “thiol” Remember to keep the e Common names are alkyl mercaptans

Physical Properties-Thiols The difference in electronegativity between S (2.5) and H (2.1) is 0.4. This creates a bond with low polarity show little association by hydrogen bonding have lower boiling points and are less soluble in water than alcohols of comparable MW

Thiols act as Nucleophiles Thiolate anions are weak bases (weaker than alkoxides) and in protic solvents are better nucleophiles (better than alkoxides since they don’t H bond)

Sulfides or thioethers Sulfur analogs are called sulfides or thioethers Most sulfides react readily to form sulfonium salts

Sulfides or thioethers The sulfonium salt easily reacts in a substitution reaction:

Organometallic Compounds So far, we have seen reaction in which carbon is bonded to a more electronegative atom. What happens when it is connected to a less electronegative atom?

Organometallic Compounds A compound that contains a carbon-metal bond Organolithium Organomagnesium (Grignard Reagent)

Organometallic Compounds

Organometalics act as nucleophiles Reactions must be carried out in very dry solvents and nothing acidic Can be in the reaction mixture

Organometallic Compounds The greater the polarity difference, the greater the reactivity of an organometalic reagent

Coupling Reactions Gilman Reaction Heck Reaction Stille Reaction Suzuki Reaction

Gilman Reagents Prepared from an organolithium reagent and copper(I) iodide Henry Gilman

Gilman Reagents Gilman reagents can be used to form new carbon-carbon bonds by cross-coupling with alkyl or aryl or vinylic halides Henry Gilman (Note: cannot use S N 2 with aryl or vinylic halides)

The Heck Reaction

The Stille Reaction

The Suzuki Coupling