Organic Chemistry II - Exam 4 (Chapters 19 and 20)

carboxylic acid nomenclature

remove e and add oic acid

what happens when carboxylic acid is dissolved in water

forms proton and carboxylate ion

what happens when carboxylic acid is treated with a strong base

carboxylate salt is formed

what happens when an alkyne is reacted with O3 and water?

oxidative cleavage occurs and breaks carbon triple bond and forms two carboxylic acids

each carboxylic acid has a R group and an OH group

Primary alcohol is reacted with what to form a carboxylic acid?

Na2Cr2O7 / H2SO4 and H2O

What reagents are used to convert an alkylbenzene into a benzoic acid?

Na2Cr2O7 / H2SO4 and H2O

What reacts with a grignard reagent to form a carboxylic acid?

grignard reagents react with carbon dioxide, then are protonated, to form a carboxylic acid

AKA CO2 insertion

SKISLOPE

Acid Halide

Acid Anhydride

Ester

Amide

Nitrile

order from most reactive and least reactive

what reagent converts carboxylic acids into acid chlorides?

SOCl2 or COCl2

also produces SO2 and HCL as byproducts

what is produced with acid chloride undergoes hydrolysis?

oxygen from water attacks carbon center

loss of a leaving group (Cl)

water deprotonates the water on the carboxylic acid

carboxylic acid with OH and R group forms

what reagent is used for the esterification of a acyl chloride

ROH

the oxygen on the ROH attacks the carbon center, and the molecule rearranges

ROH is added a second time to deprotonate and produce the ester product

acid chlorides react with what to form amides?

Amines!

NH3

primary RNH or Secondary R2NH

The nitrogen attacks the carbon center and rearranges

What reagents reduces acid chlorides?

H bond from LAH attacks carbon center

Cl group leaves

Carbonyl reforms

LAH attacks AGAIN

proton transfer occurs to add H to O on carbonyl group

If a milder LAH is used on an acid chloride, what product is produced? What reagent would this be?

Milder LAH is used to stop at the aldehyde, so LAH only attacks once

LiAl(OR)3H and Water is used

What product forms when grignard or organolithium products react with acid chlorides?

R group attacks carbon center

Cl leaves as a leaving group

R group attacks reformed carbon center

Then water protonates the oxygen on the carbonyl compound to form a tertiary alcohol

How to prepare acid anyhyride… what does carboxylic acid react with

Carboxylate attacks carbon center of carboxylic acid

Cl leaving group leaves and acid anhydride forms

What is the leaving group for acid anhydrides?

When a acid anyhyride is formed, the carboxylate ion attacks. That part serves as the leaving group and the reactions for acid chlorides are analogous to acid anhydrides

How is an ester prepared? What reagents are used? What is the process?

A carboxylic acid reacts with a strong base to give a carboxylate

The carboxylate can react in SN2 fashion with an alkyl halide to give an ester

Fischer esterification

carboxylic acid reacts with an alcohol using an acid catalyst to form an ester

the process is reversible so you remove water to give ester and add water to give an acid

fischer esterification mechanism

protonation of carbonyl group using MeOH

alcohol functions as NUC and attacks carbonyl group

positive charge is removed via deprotonation using MeOH

the OH is converted into a better leaving group (AKA water)

carbonyl group is reformed by kicking water out

positive charge is removed via deprotonation of MEOH

Hydrolysis of Ester

ester is acid catalyzed and forms an alcohol and a carboxylic acid

protonation of carbonyl group

water functions as nuc and attacks carbonyl group

positive charge removed via deprotonation

alkoky group converted to better LG

carbonyl group reformed and MEOH kicked off

positive charge is removed via deprotonation

saponification

esters undergo hydrolysis in the presene of aqeous hydroxide (NaOH and H3O)

hydroxide attacks carbonyl group

carbonyl is reformed and alkoxide is expelled

carboxylic acid is deprotonated by alkoxide ion

generating carboxylate ion

aminolysis

ester reactions with ammonia to form an amid and alcohol

what reagent reduces esters to carboxylic acids?

what reagent reduces ester to aldehydes only?

excess LAH and water or H3O reduces esters to form alcohols using carboxylic acid

DIBAH to form the aldehyde, not protonated

what do esters produce when they react with grignards or organolithium reagents?

produce an alcohol with R groups that are identical

ester reacts with first mole of grignard to form a ketone

the ketone reactions with the second mole of grignard to form an alkoxide which is protonated to form a tertiary alcohol

why doe amids require harsher conditions for their hydrolysis? do esters require harsh conditions?

amides are more table and requre harsher conditions for hydrolysis compared to that of an ester

acid hydrolysis of amides mechanism

carbonyl is protonated

water attacks carbon center

water deprotonates water

leaves OH group and acid

then NH2 is acid-catalyzed and NH3 leaves as LG

NH3 deprotonates alcohol

leaving carboxylic acid with OH group

base hydrolysis of amides mechanism

OH (addition of the nucleophile to carbonyl)

elimination of leaving group (NH2)

proton transfer (H is deprotonated from OH)

carboxylic acid formed

what reagent is used to reduce amides?

LIAlH4 can reduce an amide

carbonyl group with excess LAH and water switches carbonyl group for 2 H bonds

what happens when a primary or secondary alkyl halide is treated with cyanide ion?

the CN- group acts as a nucleophile and replaces Br with CN

prep of nitriles via dehydration

reagent used can be SOCl2

amide attacks SOCl2 (double bond of carbonyl attacks S)

loss of LG (CL) and rearragement of molecule

positive charge on nitrogen atom is removed via deprotonation

elimination of a proton from nitrogen and a leaving group leaves us with the product R-C-N

hydrolysis of nitriles (acid-catalyzed)

aqueous strong acid can be used to hydrolyze a nitrile

nitrogen is protonated many times and water acts as a nucleophile

RCN grabs proton from water

Water attacks carbon on RCN and transforms triple to double bond

positive charge removed via deprotonation via water

nitrogen atom is protonated forming a resonance-stabilized intermediate

positive charge is removed via deprotonation

hydrolysis of nitriles base-catalyzed

OH attacks RCN

N grabs proton from H2O

OH grabs proton from OH

Nitrogen attacks H2O

produces amide

how does nitrile react with grignard

R group attacks RCN and gives an anion, like an alkoxide, protonated to form an imine, when hydrolyzes to a ketone

nitriles can be converted into amines via reduction using LAH

RCN with xs LAH and H2O gives H and H and R and NH2

reagent for oxidation of primary alcohols

PCC / methylene chloride (CH2Cl2)

an aldehyde is formed and does not further oxidize the aldehyde into a carboxylic acid

ozonolysis of alkenes

reagents

O3 and DMS

a carbon double bond is cleaved

if any carbon atom bears a hydrogen atom, there will be aldehyde products

hydroboration-oxidation of terminal alkynes

reagents

1) R2B-H

2) H2O2, NaOH

results in anti-markovnikov addition of water across pi bond

followed by tautomerization

results in a enol that forms an aldehyde

reagents of oxidation of secondary alcohols

Na2Cr2O7 (chromic acid) and H2SO4, H2O

results in a ketone

ozonolysis of alkenes

alkenes that are substituted on each carbon can be cleaved to form ketones

1) O3

2) DMS

reagents of acid-catalyzed hydration of terminal alkynes

H2So4, h2o and hgso4

markovnikov addition of water across the pi bond

tautomerization to form a methyl ketone

reagents for friedel-crafts acylation

acid chloride and AlCl3

aromatic rings will react with acyl halide in presence of lewis acid to produce an aryl ketone

which are more reactive, aldehydes or ketones?

aldehydes are more reactive than ketones due to sterics and electronics

nucleophilic addition

adding a nucleophile and H to the carbonyl bond

center carbon is electrophilic, so it can be attacked from the top or the bottom

basic conditions of nucleophilic addition reactions

nucleophile attacks carbonyl

oxygen on carbonyl is protonated using water

neutral or anionic compounds expected as products

acid conditions of nucleophilic addition reactions

carbonyl is protonated using an acid

nucleophile attacks the electrophilic carbon

carbonyl group is then attacked by a nucleophile

in an aqueous solution, a ketone or aldehyde is in _____________ equilbrium with its hydrate

with ketones, what side does the equilibrium favor?

the equilibrium favors the unhydrated keto form (carbonyl form) more than for aldehydes since aldehydes are more reactive

acid-catalyzed hydration

carbonyl group is first activated by protonation

water attacks the electrophilic carbon

deprotonationi gives the hydrate (2 OH groups in total)

base-catalyzed hydration

hydroxide ion attacks carbonyl group

protonation of intermediate gives the hydrate (again 2 OH groups at the end)

general mechanism of formation of acetals

with an acid catalyst, two equivalents of alcohol will react with an aldehyde or ketone to give an acetal

formation of hemicetals

carbonyl compound is acid catalyzed

ROH attacks protonated carbonyl

intermediate is deprotonated with base

hemiacetal forms (OH and OR group present)

formation of acetals, starting from a hemiacetal

OH is protonated and leaves as H2O

compound rearrangements to regenerate carbonyl bond

ROH attacks carbonyl double bond to form another intermediate

intermediate is deprotonated and forms acetal

what reagent drives the hydrolysis of acetals

acetals can be hydrolized by adding dilute acid

diol + carbonyl compound → product + function

cyclic acetal

protect carbonyls from unwanted reactions

how to reverse cyclic acetals

add water to cyclic acetal protecting group to restore the carbonyl double bond

ammonia or primary amines + ketone/aldehyde →

imine (compound that contains c double n bond)

formation of imines mechanism

amine attacks carbonyl group

intermediate is protonated

deprotonation gives carbinolamine

OH is protonated and converted into leaving group

water leaves and c and n double bond forms

intermediate is deprotonated to generate an imine

what is the optimum pH for the formation of imines mechanism?

optimum pH is about 4.5

H2N - H

ammonia

H2N - R

primary amine

H2N - OH

hydroxylamine

H2N - NH2

hydrazine

H2N - NHPh

phenylhydrazine

H2N - NH - CO - NH2

semicarbazide

secondary amine + ketone/aldehyde + mildly acidic conditions →

Enamines

formation of carbinolamine

R2HN

amine attacks carbonyl group

intermediate protonated

deprotonation gives carbinloamine

formation of enamine from carbinolamine

OH group protonated and turning H2O into a good leaving group

water leaves and CN double bond reforms

intermediate is deprotonated (H from alpha position away from center carbon)

enamine formed

what is the difference between the mechanisms of the formation of imines versus enamines?

formation of imines uses a primary amine and results in a cyclohexane with a nitrogen double bonded with one R group attached

formation of enamines deprotionates from an alpha carbon leaving a double bond not between the nitrogen, but on a carbon chain with the nitrogen having two R group substituents

hydrazine structure

N2H4

summarize the wolff-kishner reduction

hydrazine (N2H4) attacks a carbonyl via the imine formation mechanism

this forms a hydrazone which is structurally like an amine

formation of a hydrazone mechanism (wolff-kishner reduction)

amine attacks carbonyl group which produces an intermediate with a negatively charged oxygen

the oxygen is protonated using acid, then conjugate base deprotonates the amine to form a carbinolamine

the carbinolamine is protonated using acid

water leaves as a leaving group, and double bond between C and N forms

the intermediate is deprotonated to generate an imine

what is the second step in wolff-kishner reduction?

(KOH/H2O)(basic conditions)

hydrazone is deprotonated, resonance structures form, creating a double bond between nitrogens and a lone pair on the center carbon

the intermediate is protonated at the lone pair

base deprotonates the nitrogen again

nitrogen substituent leaves as nitrogen gas and leaves a carbanion

water deprotonates this carbanion and reduces the hydrazone

hydrolysis of acetals

carbon group is protonated, making it more electrophilic

molecule of alcohol is ejected as a leaving group

water functions as a nucleophile and attacks electrophilic carbon

water functions as a base and removes a proton, giving a hemiacetal

the hemiacetal is protonated, generating an excellent leaving group

a molecule of alcohol is ejected as a leaving groupw

water functions as a base and removes a proton, giving a ketone

what is the mechanism for the hydrolysis of imines and enamines?

reverse their formation

acid-catalyzed with water produces the ketone and the original amide

thioacetals are reduced under what conditions?

they are desulfurized in the presence of Rainey-Nickel

what are two reagents and their solvents from ch 12 that function as hydrogen nucleophiles

LAH and Water

NaBH4, MeOH

in basic conditions, what are some carbon nucleophiles that will undergo addition reactions?

Grignard Reagents (source of carbon nucleophile) or HCN/KCN

what is the purpose of the wittig reaction?

converts a carbonyl group into a new double bond where a bond did not previously exist

what is considered the nucleophile of a witting reaction?

phosphorus ylide is considered the nucleophile and it attacks via SN2

formation of phosphorus ylide

triphelyphosphine attacks carbon @ alkyl halide

x is pushed off as a leaving group

butyl lithium deprotonates an H from the carbon group

negative charge from carbon in intermediate resonance form is removed by forming a double bond beteween phosphorus and carbon

mechanism of the witting reaction (ALL)

step 1

phosphorus ylide attacks ketone/aldehyde

creates an alkane with a negatively charged oxygen and positively charged phosphorus

step 2

oxygen attacks phosphorus and forms a square with lots of ring strain (oxaphosphetane)

step 3

oxaphosphetane collapse (double bond forms between carbons, and phosphorus and oxygen atom)

products form: PH3PO and alkene

in wittig synthesis, which end of the double bond comes from the ylide?

less hindered end of the double bond comes from the ylide

RCO3H

in which reaction is this reagent used?

bayer-villager oxidation of aldehydes and ketones

an oxygen atom is inserted between a carbonyl carbon and neighboring group

mechanism of bayer-villiger oxidation

ketone is protonated by an acid (peroxy acid or carboxylic acid)

protonated ketone can be attacked by peroxy acid

charged intermediate is deprotonated by conjugate base of acid

rearrangment occurs where carbonyl group is reformed

proton transferred to give an ester and carboxylic by product

product of cyclic ketone and RCO3H

lactone (cyclic ester)

rate of migration for aldehydes/unsymmetrical ketones

hydrogen over tertiary over secondary, phenyl, over primary over methyl