Reagent

Function

Notes

-OH

Good Nuc, Strong Base

Converts R-L to R-OH for 1
and activated 2 R-L

SN2 conditions, normal 2 R-L leads to E2

(use synth. eq. acetate)

-OR

Good Nuc, Strong Base

Converts R-L to R-OR for 1
and activated 2 R-L

SN2 conditions, normal 2 R-L leads to

E2. Known as Williamson Ether
Synthesis

CH3CO2

Fair Nuc, Weak Base

Is a synth. eq. for OH
(unmasked with KOH/H2O)

SN2 conditions, will work fine for any 1

or 2 R-L

Na (also Na)

Sodium metal acts as a base,

removing H+ from ROH to
create RO (alkoxide)

Harsh conditions that require p/p alcohol

as the solvent (the CA of RO)

K2CO3

Weak base used to

deprotonate (remove H+) from
phenols

Will not work for normal alcohols, only

phenols

H2SO4

Strong acid which can

protonate alcohols, allowing
SN1 ether formation

The CB of H2SO4 is not a Nuc or a

strong base

RCO2-

Fair Nuc, Weak Base (E2

competition minimized)

SN2 conditions, will work well for 1 and

any/all 2 R-L

HBr, HI

Strong acids which convert OH

into X (Br or I)

Can be used on 1 (SN2), or 2 and 3

(both SN1) alcohols

HCl

Strong acid which converts OH

into Cl

Can be used only on 3 alcohols. Must

add ZnCl2 for 1 or 2 ROH

SOCl2

Converts OH into Cl

PBr3

Converts OH into Br

All three work well for 1 and 2 alcohol

conversion. If 3 ROH, H-X is the best
reagent.

PI3

Converts OH into I
Converts a leaving group into
an NH2. This reagent is a
synthetic equivalent for NH3,
used to make 1 amines.

Known as the Gabriel Synthesis. Avoids

the problem of multiple alkylations.

Reagent

Function

Notes

LiAlH4

Gives an H which replaces a

leaving group with H

Very reactive, cannot be used around

water or alcohols

NaBH4

Gives an H which replaces a

leaving group with H

Less reactive, compatible with water or

alcohols

-CN

Fair nucleophile, weak base

SN2 reagent, works well with both 1 and

2 R-L

-C=CH
Acetylide

Good nucleophile, strong base

SN2 reagent, works with 1 only, if 2, E2

is the major product

NaNH2 or -NH2

Very strong base

Can remove H from R--C=C--H

SR or Ph3P

Fair nucleophiles, weak bases

SN2 reagents, works well with both 1

and 2 R-L

HBr or HI

Strong acids that cleave ethers

1 (SN2) and 2 & 3 (SN1)

-OH or -OR

Strong bases, Good Nuc

Lead to SN2 when 1 or 2 (aprotic); but

E2 when 2 (p/p solvent) or 3
(regardless of solvent)

t-BuO- or LDA

Sterically hindered base

Poor Nuc, leads to E2 for 1, 2, 3

(Hofmann product)

-OH, or NaNH2

Very strong basic conditions

Used to prepare alkynes (E2 twice)

H2SO4, or H3PO4,

Dehydration reaction

E1 mechanism (Zaitsev product), Watch

out for rearrangements

Na2Cr2O7
K2Cr2O7 in H2SO4
CrO3

1 ROH --> carboxylic acid

2 ROH --> ketone

Strong Oxidizing Agent

1 ROH --> aldehyde

2 ROH --> ketone

Sensitive Oxidizing Agent

H2CrO4 (Jones Reagent)

KMnO4 (often hot with H+ or OH-)

Reagent

Function

Notes

Ag2O

aldehyde-->carboxylic acid

Incompetent Oxidizing Agent

NaOCl

Only does 2 ROH --> ketone

Environmentally friendly Oxidizing Agent

HF, HCl, HBr, or HI

Acids that add H-X to alkenes

(or alkynes)

Markovnikov addition via carbocation, so

watch out for rearrangements!

H2O with H2SO4

Adds H2O to alkenes to yield

alcohols (hydration)

Markovnikov addition via carbocation, so

watch out for rearrangements!

Cl2 or Br2

Halogens that add X2 to

alkenes (or alkynes)

Use inert solvents; Follows the

borderline SN2 mechanism, results in
anti addition

Br2/H2O or Cl2/H2O

Adds 1 X and 1 OH to a C=C

(produces a product called a
halohydrin)

Anti addition (inversion) occurs through

the bromonium (or chloronium) ion, the
water attacks 3>2>1 (borderline SN2)

1)

Adds H and OH to a C=C

Markovnikov addition, with NO

rearrangements

H2O, H2SO4, Hg2+(often

HgSO4 or HgO)

Adds H and OH to an alkyne-> results in the formation of a

ketone

Markovnikov addition, an enol initially is

formed, but spontaneously tautomerizes
to the keto form as the product

1)
2)

BH3, THF
H2O2, NaOH

Adds an H and OH to alkenes

or internal alkynes

Anti-Markovnikov addition, with syn

(same side) addition; watch out for enolketo tautomerization with the internal
alkynes

1)

disiamylborane

Adds H and OH to a terminal

alkyne --> results in the final
formation of an aldehyde

Anti-Markovnikov addition, the enol

forms first, then tautomerizes the keto
form (forms aldehyde)

Adds a CH2 (carbene) to a

C=C --> forms a cyclopropane

Adds with syn addition, which is

important when product is chiral

Ch2I2 with Zn(Cu) alloy

Adds a CH2 (carbene) to a

C=C --> forms a cyclopropane

Simmons-Smith reaction; adds with syn

addition

CHX3 with strong bases

Adds a CX2 (carbene) to a

C=C --> forms a cyclopropane

Adds with syn addition; make sure to

add CX2, NOT CH2

2)

Hg(O2CCH3)2,
H2O

2)

CH2N2

NaBH4, NaOH

H2O2, NaOH
Cu2+
---------->
or or hv

Reagent

Function

Notes

RCO3H or MCPBA

Adds the 3rd (extra) oxygen to

a C=C --> forms an epoxide

Adds with syn addition, which is

important when product is chiral

1)

OsO4
KMnO4
----------> or --------->
2)Na2SO3
H2O
NaOH

Adds 1 OH group to each

carbon of a C=C --> forms diol

Addition occurs with syn (same side)

addition

1) O3
-------->
2) (CH3)2S

Breaks a C=C, adds a =O to

each carbon, called ozonolysis

Understand the retrosynthetic technique

to know what alkene underwent
ozonolysis (turn the two C=O back into a
C=C)

H2
-------->
Pd, or Pt

Breaks a C=C, adds an H to

each carbon (will convert
alkynes to alkanes when >
moles of H2 are used)

Under normal conditions, H2 does not

add to C=C in a phenyl (aromatic) ring.
Addition is primarily syn

H2
-------->
Lindlar Catalyst

Adds only one H to each

carbon of a C=C (alkyne),
converting it to an cis-alkene

Addition is syn, giving a cis-alkene.

Without a Lindlar catalyst, the reaction
cannot stop at the alkene

HNO3 + H2SO4
(Nitration)

Substitutes -NO2 on aromatic

rings

No limitations; heat reaction or use more

vigorous conditions to get disubstituted
product

O
||
CH3CCl
------------>
pyridine

Protects amines (and alcohols)

Remove group with KOH/H2O

Br2 or Cl2 + Lewis Acid

(AlX3, FeX3)
(Halogenation)

Substitutes -Br or -Cl on

aromatic rings

Requires Lewis acid unless ring is

strongly activated (e.g. phenol and
aniline, in which case, beware of
disubstitution)

H2SO4
(Sulfonation)

Substitutes -SO3H on aromatic

rings (mainly para if already
substituted

Reaction is reversible, heat in the

presence of H2SO4 and H2O remove the
-SO3H group

Reagent
R-Cl
------->
AlCl3

Function

Notes

Substitutes an (-R) on an
aromatic ring

1.

Substitutes a
/
O=C
\
R
on an aromatic ring

1.

Converts NH2 to N2, which can

be replaced by nucleophile

N2 is a good leaving group and can be

replaced with a variety of reagents

Carbocation (usually
formed by alkyl chloride AlCl3 or alcohol losing
water when acid is added)

Product of alkylation is more

reactive than starting material, often
leading to disubstitution.
2.
Rings with moderately or
strongly deactivating groups will not
undergo alkylation
3.
Watch out for carbocation
rearrangements

Friedel-Crafts Alkylation
O
||
R--C--Cl
------------>
AlCl3

2.

Very sensitive to sterics, major

product is always para
Rings with moderately or
strongly deactivating groups will not
undergo alkylation

Acyl cation (usually

formed by acetyl chloride
+ AlCl3)
Friedel-Crafts Acylation
NaNO2/H+

Reagent

Function

Notes

Nucleophile + aromatic
halide (Nucleophilic
Aromatic Substitution:
Addition-Elimination)

Nucleophile replaces halide in

a 2-step process; Nuc attacks,
and then halide leaves

The ring must have an electron

withdrawing group o- or p- to the halide.
Leaving group ability:
F > Cl > Br > I

Very strong base (e.g.

NaNH2) or base and high
heat (NaOH, )
(Nucleophilic Aromatic
Substitution: EliminationAddition)

Eliminates H-X on an aromatic

ring, creating a reactive
benzyne intermediate which
then is attacked by anion

Results in 2 different products if the ring

is asymmetric because both carbons of
the intermediate alkyne will be attacked.

H2/metal catalyst or Metal

(Fe, Sn, SnCl2) + HCl

Converts NO2 --> NH2

Important synthetic step as a diazonium

ion precursor

Reagent

Function

Notes

Clemmensen: Zn(Hg) +
HCl or
Wolf-Kishner: NH2NH2 +
KOH, or H2/metal
catalyst

Converts C=O --> CH2

H2/metal catalyst will work only if the

C=O is attached directly to the aromatic
ring

1)KMnO4, NaOH,
2) H3O+

Converts an R on an aromatic
ring --> CO2H

Reaction will not work if the substituent

C is quaternary (4)

[CN]
HCN ------------->
H2O

Adds a CN to the C and an H

to the O of a C=O, forming a
cyanohydrin

Only catalytic amounts of -CN are

needed; follows the basic mechanism

Mg or Li

Converts a R-X into a R-M;

which acts like a R-

X=Cl, Br, I; solvent must be aprotic,

usually ether or THF is used

NH4Cl

A weak acid (H+ donor) used to

protonate the Td of carbonyl
addition reactions

Avoids the E1 result for 3 alcohols

+ Ph3P--CR2

Ylide attacks C=O, resulting in

its eventual conversion to C=C
(P loves O!)

Witting reaction; BuLi is usually the base

used to make the ylide from its
phosphonium salt precursor

NR2

N attacks C=O, resulting in its

final conversion to C=N

1 amines --> imines

NH2OH --> oximes
2 amines --> enamines

H2/metal or NaBH3CN

C=N reacts more easily than

C=O, allowing conversion of
imines to amines

Either reagent can be used in the initial

reaction mixture, so the imine is never
isolated

LiAlH4

Reacts with all C=O

compounds from table 19.1

Has 4 H- available, converts C=O to CH2OH (except for ketones)

NaBH4

Reacts only with ketones and

higher on table 19.1

Has 4 H- available, can use in presence

of H2O, ROH, etc.

LiAlH(Ot-Bu)3

Converts acyl chlorides to

aldehydes at -78 C

Doesnt over-reduce to R-OH

Diisobutylaluminum
hydride (DIBAH)

Converts esters to aldehydes

at -78 C

Work up with H3O+ to complete reaction

Reagent

Function

Notes

2 mol Grignard + acyl

chloride, anhydride, or
ester

Reacts twice (cannot stop at

ketone) to yield alcohol.

Use NH4Cl as workup acid to avoid E1

elimination if 3 ROH

(R)2CuLi

Adds only 1 R group to an acyl

chloride, yielding a ketone.

Same reagent that gave conjugate

addition (Sec. 18.10)

Grignard + nitrile

Grignard adds to the nitrile

once, and the resulting imine is
hydrolyzed back to a ketone by
H3O+.

Hydrolysis is exact reverse of imine

formation (Fig. 18.3)

TsCl or MsCl

Converts -OH into -OTs or

-OMs, which are much better
leaving groups.

Reaction proceeds just like acyl

chlorides, but attack is at S

X2 w/ acid

a-halogenation of aldehydes or
ketones

reaction useful for adding only 1 halogen

x2 w/ base

a-halogenation of aldehydes or
ketones

Excess (>3 mol) of X2 will convert

methyl groups a to the carbonyl to
carboxylates (haloform/iodoform
reaction)

BuLi

Strongest base pKa = 50

Also acts like a nucleophile, so must

avoid using when C=O present

LDA, NaNH2, NaH

Very strong bases

pKa=35-38

Used to deprotonate Hs a to the C=O.

LDA is used most often because it is
totally non-nucleophilic (steric hindrance)

NaOR
NaOH

Moderate bases
pKa~16

Can be used to completely deprotonate

1,3-dicarbonyl compounds
Both reagents attack R-X as Nuc- in
typical Sn2 reactions. The final step
involves loss of CO2 gas via a 6-member
transition state (make & break bonds
around the ring). The enol which results

Reagent

Function

Notes
then tautomerizes to the more stable
keto form

1,3-dithiane attacks R-X in typical SN2

reactions or C=O carbonyl reactions.
The dithiane ring can be removed
(regenerating the C=O by adding Hg2+
in H2O
Carboxylates are oxidized at
the anode, resulting in a
fragmentation reaction where
CO2 is lost

Known as Kolbe electrolysis. Because a

high concentration of Ro forms at the
anode, the coupling reaction is
prevalent, resulting in a new R-R bond.

Replaces H with a Br at the

location of the most stable
radical.

Cl2 is too reactive (not selective enough)

to be synthetically useful.

Known as NBS. Replaces H

with a Br at the location of the
most stable radical.

NBS is especially useful when

attempting to brominate allylic systems
because it will not add (addition reaction)
to the C=C

Replaces X with H

Autoxidation - adds an OOH

group to the most stable
radical position

Not often synthetically useful, but

important in food spoilage and chemical
decomposition

Anti-markovnikov addition of
HBr to a C=C

HF, HCl, HI do NOT work well. Antimarkovnikov regio-chemistry is followed

because a more stable radical is formed

Each group adds to one side

of the C=C. The larger group
(boxed) adds first, the smaller
group adds second and goes
to the carbon which would
have the more stable radical.

Reagent

Function

Notes

Reduces benzene into 1,4butadiene (not conjugated), or

reduces the C=C of an a,Bunsaturated carbonyl, or
reduces an alkyne into a transalkene

Known as Birch reduction. Also useful in

alkylating a to the carbonyl in a,Bunsaturated carbonyl systems.