Carboxylic Acids and Derivatives Reactions and Stuff

LORD i pray this helps me!

How do you make carboxylic acids

1. Take a primary alcohol/aldehyde and Jones it (H2CrO4 H2O)

2. Add CO2 to grinard reagent, then acid workup

3. Take a nitrile CtriplebondN, hydrolysis with acid catalyst, so H2SO4, H2O, Heat to create carboxylic acid and amine. (NH3 if base, NH4+ if acid)

Reduction of Carboxylic Aicd

Only LAH or 1. LiAlH4, Et2O 2. HCl, H20 to primary alcohol

What happens when you react a carboxylic acid with an alcohol?

With an acid catalyst!! FISCHER ESTERIFICATION PADPED

How can you make a carboxylic acid into a ester?

1. Fischer esterification, turning a carboxylic acid into an ester with an alcohol and an acid catalyst (NOT base)

2. Esterification, methyl esters 

   1. Uses CH2N2, Et2O, -78 C

   2. Diazomethane, where carbanion in Ch2N2 attacks OH, taking H, then giving CH3 back, N2 leaves as leaving groups

How do you make an acid chloride?

SOCl2

(will also create HCl, SO2)

Decarboxylation

• Only happens with Carbonyl group 2 positions away in Beta Position

• Heat (Delta), -CO2

• Twist Carboxylic group, make enolate ion and take away CO2

HYDROLYSIS OF DERIVATIVES

Makes Carboxylic Acid and maybe byproducts

Very reactive Carboxylic Acid Derivative, what are they and what do they need?

Acyl Chloride and Acid Anhydride

Only neutral water

Anhydride sometimes acid catalyst (PADPED)

Less Reactive Carboxylic Acid Derivative 

1. Ester

2. Amide

3. Nitrile

4. These can hydrolyze with Take home conditions or to the doorstep conditions

Take Home Conditions

H2O, Heat, H2SO4 (Product: Carboxylic Acid)

DoorStep conditions

NaOH (Aq), Heat

Product = Carboxylate salt 

Nitrile hydrolysis ACID catalyzed mechanism

Complete from Nitrile to Carboxylic acid and NH4+ is PADPADPED

Nitrile Hydrolysis BASE catalyzed mechanism

You have to attack OH twice, Make the double O negative so that NH2 finally leaves as a leaving group. NH2 becomes NH3

Anhydrides + H2O

2 Carboxylic Acids

Esters + H2O, H2SO4 (cat.)—>

1 carboxylic acid, 1 alcohol (Reversal of FIscher esterification)

Ester + 1. NaOH, H20 2. HCl, H20

special stoichiometry

1 Carboxylic Acid, 1 Alcohol

YOU NEED A WHOLE STOICHIOMETRIC BASE (1:1 ester to base)

Amides + HCl, H20, heat

Stoichiometric equivalence of HCl needed, AND HEAT

Produces Carboxylic Acids and NH4Cl

PADPED

Amide + NaOH, H20, Heat

Carboxylate Ion Na+ and Amine H2N—PH

need Acid work up, HCl, H2O so product: carboxylic acid and NH3 + —-PH

two negative O’s in mechanism

Nitriles + H2O, HCl, Heat

Amide then 2 eqiuvalence, is Carboxylic acid.

How to write and make a carboxylic acid through C=N starting with CHxBr

1. KCN, DMSO

2. NAOH, H2O, HEAT

3. HCL, H20

Acid Chloride + ALCOHOL, what are the solvents?

You NEED pyridine or NEt3

Acid Chloride + CH3OH ——(pyridine)—→ creates what, what is the mechnaism first step??

• No catalyst required

• Amine Base is added as HCL sponge.

• Follows an Addition, Elimination pattern AND STARTS W PYRIDINE BC N IS MORE NUCLEOPHILIC THAN O (Less EN)

1. Pyridine attacks acid chloride first

2. Then Cl leaves

3. then OH attacks

4. Pyridine leaves, creating ester product.

Anhydrides + ALCOHOL + Catalyst

Creates a Carboxylic acid and an ester , which carboxylic acid can be turned into another ester w alcohol and h2so4 cat.

Transesterification

Ester and Alcohol make a new ester and alcohol (replace OR group with R group in OH) (Basically r groups of alcohol and ester switch!!)

NEEDS ACID CATALYST AND HEAT

Amides + Alcohol

NO REACTION

Acid Chloride + Ammonia, 1, 2 solvent

Pyridine, CH2CL2

Acid Chloride + NH3 (1 or 2)—→

Creates an Amide and pyridineNH+Cl (shortcut NR2 connected to carbonyl C, 1 H in Pyridine N)

NH3 Sp3 more powerful attack Carbonyl C, then deprotonate NH3

you need pyridine and ch2cl2 as solvent

Anhydrides + Ammonia, 1, of 2 Amine

1. Pyridine, Ch2Cl2 Solbvent

2. Products: Amide, Carboxylate Ion and NH4+Pyridine

3. Thing to remember, carboxylate ion is the LEAVING GROUP

ESTER + AMINE

No rxn

Amides and amines

No rxn

How to make asymmetric Anhydrides 

1. React Acid Chlorides with Carboxylate Anions

This will create Anhydride and KCl as byproduct

Solvent: Pyridine or NEt3

Have carboxylate anion attack the carbonyl c, getting rid of Cl. Customize R groups for asymmetric. 

How to make symmetric anhydrides

Take 2 Carboxylic Acids, react with P2O5, make sure to have all carbons still there, just replace OH w O and connect carbon chains

Acid Chloride and Grignard or Organolithium

Add twice to form alcohol product (tertiary)

1 eqiv will form ketone intermediate but cannot isolate

assume 2 equiv

1. CH3Li, (2 equiv), et2O

2. Hcl, H20 workup

Attack Eliminate mechanism, then protonate

Grignard and Organolithium and Nitriles

Gives Ketones, NH4+Cl

1. CH3Li, et20

2. HCL, H20.

3. Form A nitrile, Protonate Nitrile, then Imine hydrolysis(hemiaminal thenn OH)

Carboxylic Acids and Organolithium Reagents

No grinyard, just organolithium

1. Ch3Li (2 eq), Et20

2. Hcl, H20

Creates Ketones!! (And a carbonyl hydrate)

forms that di oxygen ion complex

Gilman and blank

ONLY ACID CHLORIDES TO GIVE KETONES!!!

1. (CH3)2CuLi, Et20

2. HCL, H20