Organic Chemistry II- Exam #2

Describe SN2 reactions.

• concerted

• backside attack

• inverse of configuration'

• primary substrate preferred (and tertiary is completely unreactive)

• nucleophilicity parallels basicity

Describe SN1 reactions.

• reaction is multiple steps

• carbocation intermediate

• 1st step: loss of LG

• second step: nucleophile and carbocation

• substrate: tertiary ONLY

• secondary alkyl halides go SN2

Describe E2 reactions.

• concerted

• removal of H on adjacent carbon frees up electrons to push out LG

• product is an alkene + base-h + x-

• prefers tertiary substrate

• prefers STRONG BASES

• bulky bases prefer E2 over SN2

Describe E1 reactions.

• competes with and almost always accompanies SN1

• 1st step: loss of LG

• carbocation intermediate

• ONLY tertiary substrate

• product determined by Zaitsev’s rule

• product is alkene

• no stereochem requirements

What is Zaitsev’s rule?

• in E2 and E1 reactions, the most stable alkene is produced as the major product

• results from H being removed from beta-carbon with fewer H’s attached to it

• exceptions:

  • bulky base (t-butoxide) hindered H’s

  • conjugation trumps more subbed

Describe Williamson Ether Synthesis.

• alkoxide + alkyl halide

• alkoxide: conjugate base of an alcohol (ex: CH3O-)

• follows SN2

  • bulky portion should be alkoxide to minimize competing E2 reaction

Describe elimination synthesis.

• goal: minimize substitution

  • run under E2

  • use most hindered substrate (tertiary)

    • disfavor Sn2

  • use strong, bulky base

• avoid SN1 / E1

  • because results in mixture of products which is bad

Describe R-OH → R-X (X= Cl, Br, I) reactions.

• HBr, HI, HCl works well with tertiary alcohols

• For primary and secondary alcohols:

  • PBr3, PCl3, SOCl2

  • with pyradine as a solvent

  • all convert OH to better LG

Describe R-OH → ROTs reactions.

• better and more stable LG than alkyl halides

  • sulfonate esters

    • tosylate

    • mesylate

    • triflate

  • made with acid chloride and pyradine

Describe the alcohol elimination reaction:

R-OH → alkene

• concentrated acid (H2SO4, H3PO4)

  • strong acid, crummy nucleophile

• works best with tertiary alcohols (E1)

• harsher conditions required with secondary (E1) and primary alcohols (E2)

Describe reactions of ethers.

• make good solvents (unreactive)

• acidic cleavage (HBr or HI, heat)

Describe epoxide reactions.

• addition of oxygen to alkene

  • occurs with preservation of stereochem (cis/trans)

Describe base-catalyzed epoxide reactions.

• SN2

  • LG is intramolecular

  • LG is RO-

    • poor LG

    • release of ring strain makes up for it

• trans product

  • overall anti-addition to alkene

Describe acid-catalyzed epoxide reactions.

• protonated epoxide makes better LG

  • compensates for poor nucleophile

• regiochem

  • occurs at most substituted carbon

  • increases + charge at carbon stabilizes it

  • still concerted even though it is SN1-like

• stereochem

  • SN2

Describe Grignard reagents.

• alkyl halide and Mg (metal) in ether

• anhydrous conditions required

• C-Mg bond very polar

Describe organolithium reactions.

• C-Li bond more polar than C-Mg

• formation

  • alkyl halide + Li (metal)

  • anhydrous conditions required

Describe lithium diakyl cuprates / gilman reagents.

• C-Cu bond less polar

• formation: transmetallation

  • 2 alkyl lithium + CuI

  • anhydrous

Describe organometallics as a base.

• conversion of alkyl halide to alkane

• use of organometallic as strong base

Describe addition of grignard’s to ketones.

• grignard = nucleophile

• carbonyl cation = electrophile

• product: tertiary alcohol

• two steps:

  • addition of grignard

  • addition of acid

Describe addition of grignard’s to aldehydes.

• product: secondary alcohol

• two steps:

  • addition of grignard

  • addition of acid

What is a grignard?

Grignard reagent or Grignard compound is a class of chemical compounds with the general formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl

What are the basic steps of acyl substitutions?

1st step: nucleophilic attack

• nucleophile attacks the carbonyl carbon

• tetrahedral intermediate is formed

2nd step: loss of LG

• intermediate collapses back to carbonyl compound

• expels substituent that is the best LG

Describe reactivity of carboxylic acid derivatives.

What are the three reactions that are in equilibrium?

• ester to acid

• acid to ester

• trans-esterification

all catalyzed by H+, reversible, follow same mechanism

What are the approximate pKa values of protonated alcohols, protonated amines, alcohol, water, and carboxylic acids?

When are PBr3, PCl3, and SOCl2 used as nucleophiles?

• when primary and alcohol alcohols → R-X (substitution reaction!)

• all convert OH to a better leaving group

What is the difference between substitution and elimination reactions?

• Substitution reactions proceed with replacement with one another while elimination reactions proceed with the removal of atom or group.

• In a substitution reaction, an existing group on the substrate is removed and a new group takes its place.

• In an elimination reaction, the group is simply removed and no new group comes to take its place, and this usually results in a double or triple bond forming in the substrate instead.

What are some examples of good nucleophiles / strong bases?

• RO-, HO-, H-C(triplebond)C-, NH2-, NaH

• pKa (c.a.) > 12

• favor SN2 without SH (primary)

• favor E2 with SH (secondary and tertiary)

What are some examples of good nucleophiles / weak bases?

• Br-, Cl-, I-, F-, CH3CO2-, CN-, HS-, NH3

• favor SN2

What are some examples of poor nucleophiles / strong bases?

• (CH3)3CO- (t-butoxide)

• favor E2

What are some examples of poor nucleophiles / weak bases?

• H2O, ROH

• favor Sn1, E1

What do tosylate (-OTS), mesylate (-OMS), triflat (-OTF) look like? In what kind of reaction are they used?

• used when doing the alcohol substitution ROH → ROTS

When is POCl3 and pyridine used?

• the elimination reaction of ROH → alkene

• mild conditions

• E2 elimination

Which substitution and / or elimination reactions only proceed with tertiary substrates? Why?

• SN1 and E1

• less sterically hindered

• also makes for more stable carbocation intermediate

When does E2 favor secondary alcohols?

when there is a strong base

What mechanism does primary substrates prefer in general?

Sn2, but can still go E2 if there is steric hindrance

When working with epoxides, when does the nucleophile attack the more substituted carbon?

• When acid catalyzed: attack more subbed carbon

• when base catalyzed: attack less subbed C

  • product trans