chem 215

CrO3, H2SO4, H20 (Jones Reagent)- 1 prime alcohol

carboxylic acid

CrO3, H2SO4, H20 (Jones Reagent)- 2 prime alcohol

ketone

CrO3, H2SO4, H20 (Jones Reagent)- 3 prime alcohol

cant oxidize

CrO3 and pyridine / ClCro3 - and pyridine+ --- 1 prime alcohol

aldehyde

CrO3 and pyridine / ClCro3 - and pyridine+ --- 2 prime alcohol

ketone

CrO3 and pyridine / ClCro3 - and pyridine+ --- 3 prime alcohol

can't react

Swern Oxidation- 1 prime alcohol

aldehyde

Swern Oxidation- 2 prime alcohol

ketone

Swern Oxidation- 3 prime alcohol

can't react

Swern Mechanism

-o reaches out to positive s

-cl group leaves

-pyridine deprotonates ch3 group on s

-intramolecular grab of h, which causes c=o to form and s to leave

socl2

cl switches with oh group, same stereo

socl2 w pyridine

cl switches with oh group, flips stereo

pcl3

cl switches with oh group, flips stereo

pbr3

br switches with oh group, flips stereo

pi3

i switches with oh group, flips stereo

epoxide opening to less substituted side

strong nucleophile, basic conditions

ex: 1. NaOCH3 2. H3O+

epoxide opening to more substituted side

weak nucleophile, acidic conditions

ex: HOCH3 + H2SO4

Strong nuc examples

LiAlH4, NaBH4, CICh3, MgBrCH3

weak nuc

ketals, acetals, mines

Organometallics/grignard

often attacks c=o bonds and makes carbon great nucleophile, halogen switch

Grignard

mg, make carbon negative

organolithium

2 li, make carbon negative

hydride donors

LiAlH4, NaBH4- add h to c=o bond and with workup o becomes oh

Ketone

hemiketal

ketal

aldehyde

hemiacetal

acetal

Ketals/Acetals

need strong acid to make or go back

make ketal/acetal mechanism

1. protonate oxygen in c=o

2. new thing add

3. deprotonate new thing

4. protonate leaving group (probs oh)

5. assisted ionization

6. add new OR group

7. deprotonate

8. ketal or acetal!

making imines

ph=6

epoxidation

mCPBA

dihydroxylation

oso4, kmno4

hydroboration

bh3, h202, naoh

hydrogenation

triple bond to single, h2 & pd-c

poison catalyst

triple bond to double with z double bond, h2, caco3 or pbo

dissolving metal

triple to double with e stereo, nanh3

ozonolysis reductive

1. o3 2. zn

ozonolysis oxidative

1. o3 2. h202, naoh

Acid Chloride to Ester- Acylation- anionic nuc (strong base)

2 steps, NaOCH3

Acid Chloride to Ester- Acylation- Neutral Nuc + Catalyzed strong acid

6 steps, CH3OH + H2SO4, protonate carbonyl, neutral nuc attack, nuc deprotonated, protonate LG, assisted ionization of LG, deprotonate carbonyl

Acid Chloride to Ester- Acylation- Neutral nuc + weak base

3 or 5 steps, only works when x= good lg (cl, anhydride) and Nu-H is a strong nucleophile (amine). nuc attacks, nuc deprotonated, LG leaves

Acid Chloride to Mixed Anhydride- Acylation- anionic nuc (strong base)

2 steps, Na o-c=o-ph

Acid Chloride to Mixed Anhydride- Acylation- Neutral Nuc + Catalyzed strong acid

6 steps, Na o-c=o-ph + H2SO4, protonate carbonyl, neutral nuc attack, nuc deprotonated, protonate LG, assisted ionization of LG, deprotonate carbonyl

Acid Chloride to Mixed Anhydride- Acylation- Neutral nuc + weak base

3 or 5 steps, only works when x= good lg/reactive electrophile (cl, anhydride) and Nu-H is a strong nucleophile (amine). nuc attacks, nuc deprotonated, LG leaves

Amides can only go directly to

esters and carboxylic acids

Amide to carboxylic acid (-oh) works in

basic (1. NaOH, 2. H3O+) and acidic (H20 + H2SO4) conditions

Amide to ester- Acylation- anionic nucleophile (strong base)

not reversible w nucleophile, basically only strong acid works

Amide to ester- Acylation- neutral nucleophile and strong acid (1 equiv h2so4)

1. protonate carbonyl 2. nuc attack 3. nuc deprotonated 4. amide protonated 3. assisted ionization 4. carbonyl deprotonated by amide. (once amide protonated w positive charge, no longer accsessible as nuc)

esters and thioesters cant go back to

chlorides or anhydrides

Transesterification

ester to ester (only strong acid or strong base)

esters and thioesters- Transesterification- acylation- strong base

2 step, need excess of na och3 or other ester to drive rxn forward

esters and thioesters- Transesterification- acylation- neutral nuc (ROH) and strong acid (H2SO4)

intramolecular transesterification (favored). 6 steps. PROTONATE BEFORE LEAVING

esters and thioesters- Transesterification- acylation- neutral nuc + weak base doesn't work

HOCH2CH3 + triethylamine (DOESNT WORK)

Hydrolysis of esters (ester to carboxylic acid)

only strong base and strong acid work

esters and thioesters- ester to -oh - acylation- strong base

2 steps, needs h30+ work up step bc base will deprotonate oh group on carboxylic acid group

esters and thioesters- ester to -oh - acylation- neutral nuc and strong acid (H2SO4)

large excess of water (neutral nuc) drives rxn forward , 6 steps

esters and thioesters- ester to amide - acylation- strong base

DOESNT WORK

esters and thioesters- ester to amide - acylation- neutral nuc and strong acid

DOESNT WORK

esters and thioesters- ester to amide - acylation- neutral nuc and weak base (amide and triethylamine)

h-amide + triethylamine

Acyl Transfer Reactions- ester to carboxylic acid

use h20 + h2so4

acid chloride to carboxylic acid

use weak base conditions, 1. water/triethylamine 2. h30+

Reactions of RLi, RMgX w CO2

brings to carboxylic acid after h30+ workup

cant go from carboxylic acid to amide

must go oh to cl to amide

NaBH4 only works w

Acid Chloride, w workup brings to primary alcohol

Acid Chloride & LiAlH4

brings to primary alcohol with workup

Acid Chloride with MgBr-CH3

Reacts twice to bring to primary alcohol with workup

Acid Chloride with Ch3-Li (excess)

Reacts twice to bring to primary alcohol with workup

Esters (thioesters too) with LiAlH4 (excess)

Reacts twice to bring to primary alcohol with workup

Esters (thioesters too) with Ch3-MgBr (excess)

Reacts twice to bring to primary alcohol with workup

Esters (thioesters too) with Li-Ch3 (excess)

Reacts twice to bring to primary alcohol with workup

Esters (thioesters too) with NaBH4 (excess)

no reaction

Amides only react with

LiAlH4, swaps out carbonyl for two h's

Carboxylic Acids w NaBH4

no reaction

Amides with Mg-X or Li-X

no reaction

Carboxylic Acid with LiAlH4

Reacts twice to bring to primary alcohol with workup

Carboxylic Acid with CH3-Li

Reacts once, carbonyl maintained

Carboxylic Acid with Ch3-MgBr

no reaction

Weinreb Amide with NaBH4

no reaction

Weinreb Amide with LiAlH4

turns to an aldehyde (weinreb amide leaves)

Weinreb Amide with CH3-Li

turns to a ketone (weinreb amide leaves) (gets stuck at tetrahedral intermediate)

Weinreb Amide with CH3-MgBr

turns to a ketone (weinreb amide leaves)

Claisen

enolate +ester

Aldol addition

enolate attack aldehyde or ketone leaving alcohol bc nothing can be kicked off

Aldol Condensation

same as aldol addition, except enolate formed again to kick off alcohol leaving c=c bond

Decarboxylation (ketone and ester)

H2so4 and h20 to turn ester into carboxylic acid, heat to creat CO2 (heat yeets co2 out)

enols (strong acid)

no sn2

LiAlH4, NaBH4

1, 2 addition

Ch3Li, MgBr-CH3

1, 2 addition

Ch3Li, MgBr-CH3 with CuI

1, 4 addition

Heteroatoms

1, 4 addition