Reagent Table.doc

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=C—H 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

Doesn’t 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 H’s 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.