pkas

H3O+

<0

RCH3 … CH4 (alkanes)

50

CH3COOH (acetic acid)

5

H3COH (methanol, alcohol)

16

Phenol

10

H2SO4

-5

NH3 (amine)

38

Pyridium ion

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

(-) 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

HOCH3

Methanol (good for SN1)

The intermediate carbocation in an SN1 rxn is …

Flat

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 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

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

RDS in E1 and SN1 mech is …

Formation of a carbocation

Alkyl tosylates behave like

Bromide

E1 Alcohol Reagent

H2SO4 (Acid)

E2 OH reagent

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

Pyridine

SN1 OH reagent

HX (X = Cl, Br, I)

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 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

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

True

Alkene hydrohalogenation reagents

HX (X = Cl, Br, I)

Alkene hydration reagents

H2O

H2SO4

Alkene halogenation reagents

X2 (X = Cl or Br)

Alkene halohydrin formation

X2, H2O (X = Cl or Br)

Alkene hydroboration-oxidation reagents

1. BH3

2. H2O2, HO-

Alkene hydrohalogenation & hydration features

-Carbocation intermediate

-Acidic conditions (organic materials all positive or neutral)

-Markovnikov Addition

-Syn & Ani Addition

-Makes 1:1 racemic mixture

-Up to 4 products

Alkene halogenation & halohydrin formation features

-Halonium ions

-Acidic conditions

-Markovnikov Addition

-Anti addition

-Achiral or racemic mixture (up to 2 different products)

Alkene hydroboration-oxidation features

-Anti-Markovnikov Addition

-Retention of configuration

-Syn Addition

-Racemic mixture (has enantiomers & diastereomers)

Alkyne hydrohalogenation reagents

2 HX (X = Cl, Br, I)

Alkyne halogenation reagents

2 X2 (X = Cl, Br)

Alkyne hydration reagents

H2O

H2SO4

If terminal alkyne: HgSO4

Alkyne hydroboration-oxidation reagents

1) R2BH / BH3

2) H2O2, KOH

Alkyne hydrohalogenation features

-Markovnikov Addition

-Product: geminal dihalide

Alkyne halogenation features

-Product: Tetrahalides

Alkyne hydration features

-Acidic conditions

-Markovnikov Addition

-Product: Ketones

Alkyne hydroboration-oxidation features

-Basic Conditions

-Anti-Markovnikov

-Product: Aldehydes (sometimes ketones)

-Tautomerization is catalytic in base, so regenerate OH

Reduction

Going from a high oxidation state (more C-X bonds) to a low oxidation state (fewer C-X bonds)

Oxidation

Going from a lower oxidation state (fewer C-X bonds) to a higher oxidation state (more C-X bonds)

Reduce an alkene (hydrogenation)

-Use Pd/C, H2 (can also use D2 — when that happens, add 2 D)

-Adds Hs to both sides of the alkene bond

-Syn addition

-Makes enantiomers

Reduce an aldehyde (carbonyl)

-Use Pd/C, H2

-Adds 1 H to O & 1 H to C in C=O bond

-1 equivalent of H2 — doesn’t reduce further bc Pd/C only works on pi bonds

-No enantiomers bc 2 Hs bonded to C make it achiral

Reduce a ketone (carbonyl)

-Use Pd/C, H2

-1 equivalent of H2

-Makes enantiomers

Reducing agents

Many have Metal-H (metal hydrides)

Pd/c, H2: xPd-H

Borane: H2B-H

Borohydrides: BH4-, Na+

Aluminum hydrides: Al4-, Li+

Na0 (sodium metal, can donate an e-)

Reduce alkyne to alkane

-Pd/C, H2

-Reduce all pi bonds

Reduce alkyne to cis-alkene

-Lindlar’s catalyst (poisoned Pd/C), H2

-Syn addition

Reduce alkyne to trans-alkene

-Na0, NH3

-Anti addition

Reduce alkyne to trans-alkene mechanism

1. Na0 + NH3 makes Na+ & e-

2. Alkyne bond attacks e- & e- attacks a C. The alkyne bond donates 1 e- to the other C, forming a carbon radical and carboanion.

3. Carboanion dep+ates NH3

4. Carbon radical & e- bond, making another carboanion

5. New carboanion dep+ates NH3

Reduce epoxides

-Use LiAlH4 (“LAH”) & H2O

-Basic conditions: attacks less sub C

-SN2 inversion

-Adds H to less sub C & O

Reduce alkyl halides & sulfonates

-LAH

-Replaces X (Cl, Br, I) or OTs with H

Reduce alkyl halides & sulfonates mechanism

H from -AlH4 attacks C, kicking off the LG. This makes the product, Li+, LG-, and AlH3

Stereospecific

Starting materials with diff configs lead to stereoisomerically distinct products (Toyota)

Exclusive product formation bc of mechanism

Ex:

E2 - APP req.

SN2 - always inversion

Pd/C, H2 - Syn addition

Common oxidants

M-O (metal-O) or O-O (very weak bond):

-mCPBA

-OsO4

-O3

-PCC

-Jones

Epoxidation reagents

mCPBA

Epoxidation features

-SN2 synthesis

-Stereospecific

-Enantiomers

-Syn addition: adds C-O bond on same face

-Turns alkene bond into Epoxide ring

Dihydroxylation to form syn-diol reagents

1. OsO4

2. NaHSO3, H2O

Dihydroxylation to form syn-diol features

-Syn addition

-Enantiomers (racemic)

-Both C-O bonds formed from OsO4, same face of alkene

Dihydroxylation to form anti-diol reagents

1. mCPBA

2. KOH

Dihydroxylation to form anti-diol features

-Basic conditions

-Anti addition

Oxidative Cleavage of Alkene Reagents

1. O3

2. Me2S (or Zn)

Oxidative Cleavage of Alkenes features

-Forms aldehydes or ketones

-2 carbonyls for each alkene (when part of ring, can be connected)

Oxidative cleavage of alkynes reagents

1. O3

2. H2O

Oxidation of alcohols reagents

PCC (forms aldehyde if 1 prime and ketone if 2 prime)

Jones (forms carboxylic acid directly)

Oxidation of aldehyde reagents

Jones (forms carboxylic acid, doesn’t work on ketones)

Protonated carboxylic acid pka

<0

Carboxylic acid