pkas

H3O+

-2

HCR3 … CH4 (alkanes)

50

CH3COOH (acetic acid)

5

H3COH (methanol, alcohol)

16

Phenol

10

H2SO4

-5

NH3 (amine)

38

5

HCN

9

Phenylacetylene

25

H2

40

HCl

-7

HBr

-9

Triethylammonium ion

11

HI

-10

HN3

5

HF

3

HOH/H2O

15

Good LG

EN & polarizable

Low pka value

The TS for an SN2 rxn is

trigonal pyramidal

Williamson Ether Synthesis (SN2)

RO- + alkyl iodide —> ether

SN2 mechanism

1. Nuc: (usually negative) backside attacks the alpha carbon, which displaces the LG and causes inversion of configuration

SN2 wants

1. Sterically unhindered E+ (methyl, primary, secondary)

2. Good LG (EN and polarizable, low pKa)

3. Very basic Nuc: (high pKa)

4. Sterically unhindered Nuc: (no tertiary)

SN1, SN2, E1, and E2 require a(n) ___ hybridized E+

sp3

(-) charged Nuc: (usually SN2)

-OH, -OR, CH3CO2-

N3-

-CN HC≡C-

Cl- Br- I-

HS- RS-

Neutral Nuc: (SN1)

H2O ROH

NH3 RNH2

H2S RSH

SN1 mechanism

1. LG leaves, creating a carbocation

2. Nuc: attacks the alpha carbon & bonds to it with a positive charge. It can attack from the top or bottom, leading to a racemic mixture

3. Another Nuc: or LG molecule) use Nuc: if in solution) deprotonates the Nuc: bonded to the alpha carbon

HOCH3

Methanol (good for SN1)

The intermediate carbocation in an SN1 rxn is …

Flat

Carbocation stability

Tertiary = secondary benzylic > secondary allylic > secondary > primary (very rare)

Secondary vs secondary benzylic vs primary

Fastest SN1: secondary benzylic > secondary > primary

Fastest SN2: primary > secondary benzylic > secondary

An SN1 rxn wants

1. Stable carbocation (secondary and above)

2. Good LG (low pka)

3. Okay/neutral Nuc: (Structure doesn’t matter)

KOtBu

Potassium t-butoxide (good for E2)

E2 rxns like ___ bases

strong bases:

K+ -OtBu

Na+ -NH2 (alkynes)

DBU

E2 mechanism

1. Nuc: deprotonates, C-H bond forms a C=C bond, kicks off LG

E2 requires ____ configuration of deprotonated H & LG

Antiperiplanar (180 degrees from each other in Newman projection)

E2 is always an anti elimination!

Terminal alkene

Alkene at very terminus of alkyl chain

Alkene stability

Tetrasubst > Trisubst > Geminal (1,1) > Trans > Cis > Monosubst >

E2 wants:

Tertiary alkyl halide

Good LG (I > Br > Cl)

Big, strong base (high pka)

Trans

E

Cis

Z

E2 is very selective — draw …

only major product (for disub, trans alkene)

E1 is not as selective — draw …

all products (E, Z, terminal alkene, etc)

We have mixtures of both SN1 and E1 bc

they’re linked & completing in the same flask

E1 Mechanism

1. LG leaves and forms a carbocation

2. Nuc: attacks electrophilic C

3. Nuc: is dep+ated

RDS in E1 and SN1 mech is …

Formation of a carbocation

SN2 likes

Methyl > 1 > 2 alkyl halide

I > Br > Cl LG

Strong base (high pKa)

Small nuc:

SN2 Nuc:

(-) :C≡C-R

(-) O-Et

(-) C≡N

CH3COO(-)

E2 likes

Tertiary

I > Br > Cl

Strong base (high pKa)

Bulky base

SN1 & E1 (together) like

Tertiary E+

I > Br > Cl

Weak base (low pka)

Neutral base

E2 bases

KOtBu (see this —> probably E2)

NaNH2 (2x, used for alkynes)

DBU

SN1 & E1 bases

HOEt

HOH

CH3COOH

HOCH3

Alkyl tosylates behave like

Bromide

Dehydration

Get rid of H2O

E1 Alcohol Reagent

H2SO4 (Acid)

E1 OH Mech

1. OH on E+ dep+ates H2SO4

2. H2O leaves, forming a carbocation

3. LG H2O dep+ates E+ & C-H bond donated its e-s to form a new pi bond

If two CD3 and two CH3 groups are on an alkene, trans and cis are a 1:1 mixture because

their size is identical! CD3 is just slightly heavier than CH3

E2 OH reagent

POCl3 (not acid or else we would form a carbocation)

Pyridine

SN1 OH reagent

HX (X = Cl, Br, I)

SN1 OH Mech

1. OH on E+ dep+ates Nuc: (H-Cl), pushing e-s onto Cl

2. H2O group leaves

3. Cl- from dep+ated Nuc: attacks electrophilic C

Pyridine can/cannot deprotonate an alcohol

cannot!

Pyridium pka = 5

H2O pka = 15

SN2 OH reagent

SOCl2 + pyridine (Cl substitution)

PBr3 + pyridine (Br substitution)

Alkyl tosylate OH reagent

TsCl

Pyridine

Epoxide basic conditions facts

-SN2 to break open ring: use all good SN2 Nuc:s —> -C≡N, -C≡C-R, CH3COO-, -OEt

-Attack less subst C

Epoxide basic conditions reagents

1. (-) :Nuc

2. H2O

Epoxide basic conditions mechanism

1. Nuc: attacks least subst C, breaking C-O bond & pushing e-s onto O. If there are substitutents on the least substituted C, they shift up

2. (-) O de+ates H2O

Epoxide acidic conditions facts

-Still SN2, but use acids instead

-Attack most substituted C

-Acidic conditions, so all organic media (+) or neutral —> no alkoxide anions!

Epoxide acidic conditions reagents

1. HOEt / H2SO4 / HBr / HCl etc

Epoxide acidic conditions mechanism

1. O dep+ates H-Cl, pushing e’s onto Cl

2. Cl- attacks more substituted C, severing C-O bond and pushing e-s onto O

True or False: H-Cl is NOT H+. H+ doesn’t exist because it’s always ligated by smth in solution!