chem232 - exam 3 - mechanisms

reagents to convert alkyl halides into alcohols and mechanism

• methyl/1-unhindered - NaOH SN2

• 1-branched/2 - NaOAc, NaOH SNAC

• 3 - H2O SN1

SnAc Mechanism

only esters and carboxylic acid

→ OH attack c.a break double bond —> regenerate double bond kick of LG

fisher esterification

alcohol synthesis - special snac mechanism

acid/base (activation of carboxylic acid) → snac 1 → acid base → snac 2 → acid base

epoxide formation

halohydrin (alcohol + -X) + strong base (-OH) → []

epoxide opening (basic conditions)

SN2 → attack least substituted alpha C

stronger acids than -OH

inversion, O replaced with Nu and ring is open

epoxide opening (acidic conditions)

still SN2 → MORE substituted side gets attacked

strong acid required (H2SO4, poor nu)

inversion, O replaced with nu and ring is opened

ether synthesis

methyl → SN2

1 → SN2 or E2

2/3 → SN1/E2

symmetric ether synthesis

strong acids → HCl, HBr, HI, H2SO4

product is ether with same R group attached on either side

asymmetric ether synthesis

similar reactivity produces mixtures

differing reactivity channels towards one product

dehydration (elimination)

m.p always the most stable alkene

start with OH, use H2SO4 (non-nucleophilic acid, or TsOH)

removed alcohol, has double bond

nucleophilic acids and ethers

favor substitution

remove OH and replace with X (halogen)

methyl/1 → SN2

2/3 → SN1

works to cleave ethers as well

specialized reagents for alcohol activation (creating better LG)

PBr3/PCl3

SOCl2 (thionyl chloride)

Sulfonyl Chlorides (ClMs, ClTs, TfOTf)

PBr3/PCl3 Mechanism

SN2 → inversion at alpha C

replace OH with halogen but inversion occurs

SOCl2 Thionyl Chloride Mechanism

SNAC, acid/base, SN2 → inversion at alpha C

replace OH with Cl with inversion

Sulfonyl Chlorides (ClMs, ClTs, TfOTf) Mechanism

retention! no inversion occurs: SNAc acid/base

-OH becomes -OMs or -OTs or -OTf

reagents to form new C-H bonds

LiAlH4, NaBH4

reagents to form new C-C bonds

organometallic reagents

• grinard reagent (R - MgBr)

• organolithium (R - Li)

• terminal alkene (R-C - - - CNA)

these can only attack carbonyls and epoxides!!

reagents that form C=O bonds (oxidation)

PCC (CrO3, HCl, pyridine)

Jones (CrO3, H2SO4, H2O)

Tollens (Ag2O, NH4OH, H2O)

PCC (pyridinium chlorochromate)

reagents: CrO3, HCl, pyridine

turns 1-OH into aldehydes

turns 2-OH into ketones

(essentially removes H from alcohol and turns it into C=O)

SnAc, acid/base, E2

needs protons in alpha C to the alcohol

Jones Reagents

reagents → CrO3, H2SO4, H2O → chromic acid

converts 1-OH → carboxylic acid

converts aldehydes → carboxylic acid

converts 2-OH → ketones

SnAc, acid/base, E2

needs protons in alpha C to the alcohol

Tollens Reagents

reagents → Ag2O, NH4OH, H2O

selectively turns aldehydes into carboxylic acid

generating enolates

start w/ ketone/aldehydes + -OH, do an addition (hydride)

[] forms (O- and C=C)

generating enols

start w/ ketone/aldehydes + H2SO4, protonate, do an addition (hydride)

produce [] so it has C=C and OH)

adol addition

MEAN - make enolate, addition, neutralize

produces beta-hyrdoxy carbonyl

→ O=C bond next to OH bond

→ neuclophile structure stays add bond between alpha carbon and new alcohol group carbon and keep the electrophile structure minus its original double bond

adol condensation

MEAN + EEL

do adol addition, get beta-hydroxy carbonyl then do EEL (enolate, eliminate LG)

end product should have no alcohol but have C=O and C=C bonds next to each other (conjugation)

do when you have NaOH and heat, plus some nu

crossed/asymmetric adol rxn

can produce multiple structures as they can be either nu or E-LG

general pattern is nu stays the same, E-LG C=O loses the O and becomes C=C in new structure

Claisen-Schmidt Condensation

ensures one condensation partner acts as only the electrophile

→ one group has alpha C -H bonds and the other one doesn’t

adol additions

begin with alpha, beta - unsaturated carbonyl

1,2 addition - strong bases (more than -OH) (faster) - attacks C+ at old C=O bond (keeps c=c bond)

1,4 addition - weak bases (includes gilman reagent: LiCu-R2) (slower) - attacks C+ at alcohol carbon connection (keeps c=o bond)