Goals for the day: Grignard Reaction Ethers (Naming and reactions) Epoxides (naming and reactions) Thiols & sufides (reactions)

17.5 Alcohols from Carbonyl Compounds: Grignard Reagents Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX Grignard reagents react with carbonyl compounds to yield alcohols

Mechanism of the Addition of a Grignard Reagent Grignard reagents act as nucleophilic carbon anions (carbanions = : R) in adding to a carbonyl group The intermediate alkoxide is then protonated to produce the alcohol

Try to predict the products…

Possible depictions are…

Try to fill in the mechanism…

Reactions of Grignard Reagents with Carbonyl Compounds

Reactions of Esters and Grignard Reagents Yields tertiary alcohols in which two of the carbon substituents come from the Grignard reagent Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

Grignard Reagents and Other Functional Groups in the Same Molecule Cannot be prepared if there are reactive functional groups in the same molecule, including proton donors

Predict the product…

Remember it goes all the way to the alcohol & two CH3 groups are added…

Naming Ethers Ethers contain the R-O-R bond. Basically, you name the two groups attached to the oxygen (alphabetically) and add the term ether. The smallest ether is dimethyl ether

Ethers as attachments Methoxy Ethoxy isopropoxy

Pick one to try to name & panel submit

Pick one to try to name & panel submit Secbutyl vinyl ether Or 1-secbutoxy ethene Isopropyl pheny ether Or Isopropoxy benzene

Properties of Ethers R–O–R ~ tetrahedral bond angle Oxygen is sp3-hybridized Oxygen atom gives ethers a slight dipole moment Not very reactive, so they make good solvents (diethyl ether is the “ether” we use in lab all the time).  Not water soluble (although diethyl ether is slightly…see diagram on the following page)…

This is why you have to “dry” the organic layer in your reactions!

18.2 Synthesis of Ethers Diethyl ether prepared industrially by sulfuric acid–catalyzed dehydration of ethanol – also with other primary alcohols

18.2 Synthesis of Ethers Works really only if the ether that you want is symmetric….otherwise you can get mixed results..

Need for an unsymmetric ether synthesis Problem is.....propanol reacts with itself and ethanol reacts with itself…

Mechanism of ether formation from alcohols…

The Williamson Ether Synthesis Reaction of metal alkoxides and primary alkyl halides and tosylates Best method for the preparation of unsymmetric ethers Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH

Predict the product...

The carbons of the alkyl halide become the “second” group of the ether...

An SN2 process… Note that the second step of the reaction is an SN2 process, so works best for primary alkyl halides (or methyl bromide)

Which is better? (you get phenyl propyl ether either way)…

Path “a” is better because the alkyl halide is primary and will react faster in the SN2 reaction

Cyclic Ethers Cyclic ethers behave like acyclic ethers, except if ring is 3-membered Two common structures are ethylene oxide and THF

Epoxides (Oxiranes) Also called epoxides

Preparation of Epoxides Using a Peroxyacid Treat an alkene with a peroxyacid Abbreviation for this reagent is MCPBA…

What’s the product?

Answer…

Epoxides from Halohydrins Addition of HO-X to an alkene gives a halohydrin Treatment of a halohydrin with base gives an epoxide Intramolecular Williamson ether synthesis

18.6 Reactions of Epoxides: Ring-Opening Water adds to epoxides with dilute acid at room temperature Product is a 1,2-diol (on adjacent C’s: vicinal) Mechanism: acid protonates oxygen and water adds to opposite side (trans addition)

Halohydrins from Epoxides Anhydrous HF, HBr, HCl, or HI combines with an epoxide Gives trans product

Regiochemistry of Acid-Catalyzed Opening of Epoxides 1) Nucleophile preferably adds to less hindered site if primary and secondary C’s 2) Nucleophile adds to a tertiary carbon because of carbocation character 1) 2)

Steps of Acid-Catalyzed Opening of Epoxides Protonation Attack of the nucleophile from the backside Note: check for degree of substitution

Base-Catalyzed Epoxide Opening Strain of the three-membered ring is relieved on ring-opening Hydroxide cleaves epoxides at elevated temperatures to give trans 1,2-diols

Addition of Grignards to Ethylene Oxide Adds –CH2CH2OH to the Grignard reagent’s hydrocarbon chain Acyclic and other larger ring ethers do not react

18.7 Crown Ethers Large rings consisting of repeating (-OCH2CH2-) or similar units Named as x-crown-y x is the total number of atoms in the ring y is the number of oxygen atoms 18-crown-6 ether: 18-membered ring containing 6 oxygen atoms Central cavity is electronegative and attracts cations

18.8 Thiols and Sulfides Thiols (RSH), are sulfur analogues of alcohols Named with the suffix -thiol SH group is called “mercapto group” (“capturer of mercury”)

Thiols: Formation and Reaction From alkyl halides by displacement with a sulfur nucleophile such as –SH The alkylthiol product can undergo further reaction with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol

Sulfides Sulfides (RSR), are sulfur analogues of ethers Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy

Oxidation of Thiols to Disulfides Reaction of an alkyl thiol (RSH) with bromine or iodine gives a disulfide (RSSR) The thiol is oxidized in the process and the halogen is reduced Cysteine amino acid forms cystine bonds

Sulfides Thiolates (RS) are formed by the reaction of a thiol with a base Thiolates react with primary or secondary alkyl halide to give sulfides (RSR’) Thiolates are excellent nucleophiles and react with many electrophiles

Have a wonderful day! 

Ethers and Their Relatives An ether has two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom, R–O–R Diethyl ether is used industrially as a solvent Tetrahydrofuran (THF) is a solvent that is a cyclic ether Thiols (R–S–H) and sulfides (R–S–R) are sulfur (for oxygen) analogues of alcohols and ethers