UW Madison Chem 345 Exam 3

reagents for esterification of a carboxylic acid

alcohol and acid

reagents for saponification

NaOH and H2O (and acidic workup)

what does saponification do?

turn an ester into a carboxylic acid

what is the ideal ring size for a lactone?

5

reagents for hydrolysis of amides

water and heat OR base and heat

what is the product of hydrolysis of amides in acidic solution?

a carboxylic acid

what is the product of hydrolysis of amides in basic solution?

an amine and a carboxylate ion

reagents for hydrolysis of nitriles

base, water, heat

what is the product of hydrolysis of nitriles?

a carboxylic acid

why doesn't hydrolysis of nitriles stop at the amide?

the amide is more reactive

what is the intermediate for hydrolysis of nitriles? what does that look like?

imidic acid, looks like carboxylic acid except the double bond is to an NH, not an O

what are the products of hydrolysis of acyl chlorides?

carboxylic acid and HCl

what are the products of hydrolysis of anhydrides?

2 eq of carboxylic acid

what is the order of reactivity of CA derivatives to nuc acyl substitution? (amides, nitriles, acid chlorides, acid anhydrides, esters/CA's)

acid chlorides > acid anhydrides >> esters/CA's > amides > nitriles

reagents used to turn a carboxylic acid into an acid chloride?

SOCl2 or PCl5

if you treat an acid chloride with an amine, what do you get?

an amide

if you treat an acid chloride with an alcohol, what do you get?

an ester

if you treat an acid chloride with an acetate, what do you get?

acid anhydride

what do you get if you treat an ester with NH3?

an amide

what do you get if you treat an anhydride with an amine?

an amide

what can you use to turn a nitrile into an amine?

Raney Ni w/ H2 and Ni-Al

OR

1) LiAlH4

2) H3O+/H2O

3) -OH/H2O

what can you use to turn an ester into an alcohol?

1) LiAlH4/Et2O

2) H3O+/H2O

what can you use to turn an amide into an amine?

1) LiAlH4 (excess)

2) H3O+/H2O

3) -OH/H2O

what can you use to turn an acid chloride into an aldehyde?

H2, Pd/C and base

is ester hydrolysis reversible?

no

what stabilizes a tetrahedral intermediate?

resonance, good orbital overlap/size match, polar effect of LG

are reactions of acid chlorides with ammonia/amines reversible?

no

does LiAlH4 reduce ALL carboxylic acid derivatives?

yes

what is the product of reacting a grignard and an ester?

tertiary alcohol

what is the intermediate of the reaction between an ester and a grignard?

ketone

are the more stable carboxylic acid derivatives MORE or LESS acidic?

less

what types of molecules are more stable in their enol form?

phenols and anyhdrides

what is the result of alpha halogenation of carbonyl compounds?

halide added to alpha position (mix of steroisomers)

reagents for alpha halogenation

Cl2 or Br2 and acid

reagents for haloform reaction

ketone SM, Br2, NaOH, H2O

what does the haloform reaction do?

turns a ketone into a carboxylic acid

if you react a ketone with I2 and base, what is the product?

carboxylate ion

reagents for alpha bromonation of carboxylic acids (HVZ reaction)?

PBr3 (cat) and Br2 (1 equiv)

product of HVZ reaction?

carboxylic acid with bromine at alpha position (mix of stereoisomers)

reagents for aldol addition w mild, basic conditions?

NaOH and H2O

reagents for aldol addition w acidic conditions?

H3O+/H2O

reagents for aldol addition w harsh, basic conditions?

NaOH, H2O and high temp

mechanism for aldol addition w harsh, basic conditions?

E1 CB mech

starting materials for crossed aldol (Claisen Schmidt)

aldehyde without alpha H + ketone with alpha H

reagents for crossed aldol (Claisen Schmidt)

acid OR base

reagents for Claisen condensation

1) NaOR/ROH

2) H3O+

what is the minimum number of alpha H's that the Claisen condensation starting material must have for the reaction to proceed?

2

what is the starting material for aldol condensation?

ketone or aldehyde

what is the starting material for claisen condensation?

ester

what are the reagents for malonic ester synthesis?

1) NaOR/ROH

2) SN2 substrate

3) NaOH/H2O

4) H3O+/H2O

reagents for direct alkylation?

1) LDA, THF

2) DMSO, SN2 substrate

what is an enolate?

compound with a deprotonated alpha c

reagents to make an amine from an amide or nitrile

1) LiAlH4

2) H3O+/H2O

3) -OH/H2O

is the LP on an amide or an amine more reactive?

amine

product of reacting an amine with Me-I?

quarternary nitrogen salt

intermediate for reductive amination?

imine

what can be the starting materials for reductive amination?

an amide OR a ketone/aldehyde w/ an amine

reagents for Borch reduction

1) NaBH3CN/HOAc

H3C-CN, H2O

2) KOH

starting materials for Borch reduction

amine and ketone or aldehyde

product of Borch reduction

tertiary amine

reagents for Hofmann elimination?

1) SN2 substrate, heat, Et2O

2) Ag2O*H2O

3) heat

product of Hofmann elimination?

amine replaced with least substituted double bond

why is the NH2 group meta directing in nitration?

when it is protonated by the acidic solution, it becomes an EWG, and therefore, a meta director

if you treat a benzene with an NH2 substituent with excess Br2, what is the result?

tribromonation at ortho and para positions

how can you make the NH2 only a para director for nitration?

treat it with an acid chloride, then do the nitration

reagents for diazotization?

NaNO2, HCl and a nucleophile

what does diazotization do?

turn -NH2 into -N2+

is the Sandmeyer reaction Sn2 or Sn1?

neither

possible nucleophiles for the Sandmeyer reaction?

CuCl, CuBr, CuCN, KI

reagents to turn -N2+ into -OH?

CU2O, H2O

Cu(NO3)2

reagents to turn -N2+ into an H?

H3PO2 and water

product of NaNO2 oxidation of a secondary amine?

nitrosamine (R-NR-N=O)

product of NaNO2 oxidation of a tertiary amine?

add -NO group para to the amine group

reagents for reducing NO2 compounds

H2, Pd/C

EtOH

Sn or Fe w/ HCl

1) LAH, ether

2) H3O+/H2O

starting material for Gabriel amine synthesis?

phthalimide

reagents for Gabriel amine synthesis?

1) KOH, EtOH

2) Sn2 substrate

3) HBr, AcOH, H2O

product of Gabriel amine synthesis?

primary amine

reagents for Curtius rearrangement?

1) NaN3

2) heat

product of Curtius rearrangement?

isocyanate (R-N=C=O), which can go on to react further

what can isocyanates react with?

primary amines, water and alcohols

product of isocyanate with a primary amine?

urea derivatives

product of isocyanate with water?

primary amine and CO2

product of isocyanate with an alcohol?

carbamate ester

starting material for Hofmann rearrangement?

amide

reagents for Hofmann rearrangement

Br2 and NaOH (aq)

product of Hofmann rearrangement

isocyanate, which reacts with water in the aqueous environment to form an amine and CO2

is N2 or Br a better leaving group?

N2

what is the LG in the Hofmann rearrangement?

Br

what is the LG in the Curtius rearrangement?

N2

can you isolate the isocyanate in the Hofmann or the Curtius rearrangement?

Curtius

reagents for the Darapsky degradation?

1) H2N-NH2

2) NaNO2, HCl

3) heat

4) H2O

product of Darapsky degradation?

amino acid (protonated N, deprotonated O)

Is pyridine good for SnAr or EAS?

SnAr

is pyrolle good for SnAr or EAS?

EAS

In EAS nitration, do pyrolle, oxygen and sulfur direct to the 2 or 3 position? Why?

2 position, N LP can stabilized the + charge in the ring

does a heterocycle with an S, O or NH have the fastest reaction in EAS nitration? Why?

NH, good orbital overlap and lower electronegativity

does a ring w/ N(Me)2, OMe or SMe substituent react fastest in EAS? Why?

N(Me)2, good overlap and lower electronegativity

where does pyridine direct in EAS?

meta

is pyridine deactivated or activated to EAS compared to benzene? why?

deactivated, N is an EWG which destabilizes adjacent carbons

What can you use to activate pyridine to EAS as a para director?

H2O2 and carboxylic acid