Orgo 2 Exam 2 (Chapters 16-17)

properties of a carbonyl carbon

-electrophilic (electron poor)

-sp2 hybridized

-trigonal planar geometry

-120° bond angles

What is the dipole moment of a carbonyl?

µ = 2.24 D (strong, polar)

What is the dipole moment of water?

µ = 1.85 D

IUPAC Aldehyde naming

1. Find the parent chain: the name will be based on the name of the parent alkane (drop the ending -e) with the addition of the ending "al"

-Do not need to specify the location of the singular aldehyde because it is at carbon 1

2. Then identify location of other substituents, stereochemistry, and chirality

IUPAC Ketone naming

1. Find the parent chain: the name will be based on the name of the parent alkane (drop the ending -e) with the addition of the ending "one"

2. Indicate the location of the carbonyl carbon: Number the chain to give the the ketone's carbonyl carbon the lowest number possible

3. Then identify location of other substituents, stereochemistry, and chirality

What is the common name of methanal?

formaldehyde (aldehyde with two hydrogens bonded to the carbonyl carbon)

What is the IUPAC name of formaldehyde?

methanal (aldehyde with two hydrogens bonded to the carbonyl carbon)

What is the common name of ethanal?

acetaldehyde

What is the IUPAC name of acetaldehyde?

ethanal

What is it called when an aldehyde is directly bonded to a ring as a substituent?

carbaldehyde (name of the ring structure followed by "carbaldehyde")

How do you name a carbaldehyde?

name of the ring structure followed by "carbaldehyde"

acetophenone

know structure

benzophenone

know structure

a ketone where both the substituents on the carbonyl carbon are a benzene ring

Name the two common acyl groups?

1. Acetyl group (AC)

2. Formal group

What is an acyl group?

a functional group derived from a carboxylic acid (or other organic acid) by removing a hydroxyl (-OH) group

-imagine this group as a substituent on a molecule

What is the structure of a acetyl group?

H3C-C(=O)--------

What is the structure of a formal group?

H-C(=O)--------

IUPAC Functional group naming order of priority

highest

1. Carboxylic acid

2. Aldehyde

3. Ketone

4. Alcohol

5. Amine

6. Thiol

lowest

How do identify the common name for a ketone?

name the two groups bonded to the carbonyl carbon (in alphabetical order) followed by "ketone"

What happens to hybridization at the carbonyl carbon in a nucleophilic addition reaction of an aldehyde/ketone?

carbon goes from sp2 to sp3 hybridized

Common strong nucleophiles

1. hydroxide (-OH)

2. Hydride (-:H)

3. Alkoxide (-OR)

4. Alkylide (-:R)

5. Cyanide (-:C≡N:)

6. Thiolate (-SR)

notice how all these strong nucleophiles are anionic

What is one reactivity different between strong and weak nucleophiles in addition reactions?

strong nucleophiles: add irreversibly

weak nucleophiles: can add/come off reversibly

Weak nucleophiles

1. Water (H2O)

2. Alcohol (ROH)

3. Amine (NR3)

4. Thiol (RSH)

notice how no weak nucleophiles are anionic

What is the only strong nucleophile that can add and come off reversible in a nucleophilic addition reaction?

cyanide (-:C≡N:)

Are aldehyes or ketones more reactive? Why?

aldehydes

-less sterically hindered

-more electrophilic

Why are ketone less reactive than aldehydes?

because ketones have 2 R groups that both contain at least one carbon atom, they experience more stabilization via hyperconjugation --> this stabilized the partial charges so the carbonyl carbon of a ketone is less electropositive than aldehyde's carbonyl carbon

What is a nucleophilic acyl addition reaction?

reaction where a nucleophiles makes a new bond to the electrophilic carbonyl carbon atom

-this is a characteristic reaction mechanism of carbonyl containing compounds like aldehydes and ketones

What are the five carbon nucleophilic additions

1. Grignard reagent additions to make alcohols

2. Organolithium additions to make alccohols

3. Alkynide anion addition to make α-hydroxy alkynes

4. HCN additions to make cyanohydrins

5. Wittig reaction

Grignard reagent additions to aldehydes/ketones reaction (details)

Grignard reagent can react in a two step reaction with an aldehyde/ketone to make an alcohol

-alkoxide intermediate (protonated by an aqueous acid in the 2nd step to become an alcohol)

-Exact type of aldehyde/ketone that reacts determines the degree of alcohol product that will be produced

carbonyl group becomes the alcohol

Grignard reagent additions to aldehydes/ketones reaction mechanism

1. Grignard reagent C-Mg bond attacks the carbonyl carbon, bond to oxygen breaks and electrons go to the oxygen --> alkoxide

2. aqueous acid protonates alkoxide --> alcohol

What type of reactants lead to alcohols with different degree of substitution in a Grignard reaction with aldehydes and ketones?

formaldehyde --> 1° alcohols

other aldehydes --> 2° alcohols

ketones --> 3° alcohols

What does a Grignard reaction with other aldehydes generate?

2° alcohols

What does a Grignard reaction with formaldehyde generate?

1° alcohols

What does a Grignard reaction with ketones generate?

3° alcohols

What is a homologation reaction

any reaction where the carbon chain is extended by one carbon atom

Organolithium additions to aldehydes/ketones reaction (details)

Organolithium can react in a two step reaction with an aldehyde/ketone to make an alcohol

-alkoxide intermediate (protonated by an aqueous acid in the 2nd step to become an alcohol)

-Exact type of aldehyde/ketone that reacts determines the degree of alcohol product that will be produced

carbonyl group becomes the alcohol

same reaction as the Grignard reagent*

Organolithium additions to aldehydes/ketones reaction mechanism

1. C-Li bond attacks the carbonyl carbon, bond to oxygen breaks and electrons go to the oxygen --> alkoxide

2. aqueous acid protonates alkoxide --> alcohol

same reaction as the Grignard reagent

Is a Grignard reaction or reaction with an organolithium more likely to occur?

Grignard

-these are preferred for addition reaction to aldehydes and ketones because they are easier to handle and are less reactive

Alkynide anion addition to aldehydes/ketones reaction (details)

alkynide anions can react with aldehydes and ketones in a two step reaction to make an α-hydroxy alkynes

-alkoxide intermediate (protonated by an aqueous acid in the 2nd step to become an alcohol)

-will usually have to deprotonate the terminal alkyne with a strong base to generate the alkynide anion

Alkynide anion addition to aldehydes/ketones reaction mechanism

1. alkynide anion attacks the carbonyl carbon, bond to oxygen breaks and electrons go to the oxygen --> alkoxide

2. aqueous acid protonates alkoxide --> a-hydroxy alkyne

C≡C is subject to further reaction

HCN additions to aldehydes/ketones reaction (details)

A two step reaction that involves HCN, a catalyst, and the aldehyde/ketone to get an alcohol product

-alkoxide intermediate

-reversible reaction

-NaCN (sodium cyanide) or KCN (potassium cyanide) catalyzed (catalytic amount)

-cyanohydrin formation works well for aldehydes and most ketones but not aryl ketones (low yield since reactants are favored)

-C≡N is subject to further reaction

HCN additions to aldehydes/ketones reaction mechanism

1. cyanide attacks the carbonyl carbon, bond to oxygen breaks and electrons go to the oxygen --> alkoxide

2. HCN (hydrogen cyanide) protonates alkoxide --> cyanohydrin

reaction is reversible

aliphatic

organic molecules composed of carbon and hydrogens in straight chains, branched chain, or non-aromatic rings

cyanohydrin

a molecule with an -OH and -C≡N bonded to the same carbon atom

Why is a NaCH or KCN catalyst used when making a cyanohydrin?

A catalyst is required so that there is enough cyanide anion to run the reaction

How to name cyanohydrins?

cyanohydrin of "____name of aldehyde/ketone____"

Water addition to make hydrates reaction

Water can add to aldehydes or ketone to form a hydrate (no mechanism)

-Water adds reversibly

-aldehydes hydrate to a greater extent than ketones (since aldehydes are more reactive than ketones)

-hydration reaction can be acid or base catalyzed

Can aldehyde and ketone hydrates be isolated?

no, these hydrates are not hydratable

What is a hydrate?

gem-diol (1,1 diol)

-two alcohols on one carbon atom

What is an oxygen nucleophilic addition reaction?

Addition of oxygen to a carbonyl carbon

Acetal

a molecule containing 2 -OR groups on the same carbon atom

hemiacetal

a molecule containing an -OH and and -OR group on the same carbon atom

How do you form an acetal?

a acetal is formed from a hemiactal (addition of one mole of alcohol being added to an aldehyde or ketone) that losses a water molecule and then had another mole of alcohol added to it

How do you form a hemiacetal?

a hemiactal is formed by the addition of one mole of alcohol being added to an aldehyde or ketone

Alcohol addition to a ketone/aldehyde reaction (details)

Through a complex reaction involving the addition of two moles of alcohol and the loss of water, an aldehyde/ketone can be made into an acetal

-reagents: alcohol, catalytic amount of H+ acid

-hemiactal intermediate

-reversible reaction

-reaction is acid catalyzed

-catalyst is consumed and regenerated multiple times in the reaction

-condensation reaction (loss of water)

-all reaction intermediates will be neutral or catonic/acidic (acidic reaction conditions)

Alcohol addition to a ketone/aldehyde reaction mechanism

1. protonated alcohol protonates the carbonyl oxgyen ⇄ oxonium cation

2. alcohol attacks carbonyl carbon, bond to carbon breaks and electrons go to the oxygen ⇄ oxonium cation (protonated ether)

3. alcohol deprotonated the oxonium cation ⇄ hemiacetal

4. protonated alcohol protonates the alcohol on the hemiacetal ⇄ oxonium cation

5. electrons on ether oxygen form a double bond to carbon which kicks out the water molecule ⇄ oxonium cation of a carbonyl

6. alcohol attacks the carbonyl carbon, bond to carbon breaks and electrons go to the oxygen ⇄ oxonium cation (protonated ether)

7. alcohol deprotonated the oxonium cation ⇄ acetal + acid catalyst (regenerated)

In the Alcohol addition to a ketone/aldehyde reaction, what would be the product is the reagent was a glycol alcohol?

a cyclic acetal

Acetal hydrolysis reaction (details)

An acetal can be hydrolyzed in aqueous acid to get the products of the aldehyde/ketone and the alcohols (what lead to the formation of the acetal in the reverse reaction)

-reversible reaction

-acid catalyzed conditions

-hemiacetal intermediate

Acetal hydrolysis reaction mechanism

1. H3O+ protonates one of the acetal oxygens ⇄ oxonium cation

2. lone pair on other oxygen form a carbonyl bond to kick off the cation group ⇄ oxonium cation (of carbonyl)

3. water adds to carbonyl carbon, bond to oxygen breaks and the electrons go back on oxygen ⇄ oxonium cation (protonated alcohol)

4. Water deprotonated the oxonium cation ⇄ hemiacteal

5. H3O+ protonates other acetal oxygen ⇄ oxonium cation

6. the alcohol's oxygen lone pair forms carbonyl bond which kicks off the other alcohol group ⇄ oxonium cation (protonated carbonyl oxygen)

7. H2O deprotonates hydrogen on carbonyl oxygen ⇄ acetal

in an acetal formation reaction, what is favored in an alcohol solvent?

the acetal

in an acetal formation reaction, what is favored in water solvent?

the aldehyde/ketone

reaction summary for acetal formation

1. addition of ROH --> hemiactal

2. loss of H2O, addition of ROH --> acetal

How can acetal formation reactions be driven to completion?

use of an alcohol solvent

What conditions can hemiactal formation occur under?

acid or base catalyzed

What conditions can acetal formation occur under?

acidic catalyst only

anomeric carbon

a carbon bonded to 2 oxygens

What is the only case where hemiacetals are stable?

when the hemiacetal is a 5 or 6 membered ring that is formed from a molecule that has a carbonyl and an OH on it

How can acetals be used in reactions with ketones and aldehydes?

acetals can act as carbonyl protecting groups for aldehydes and ketones

What does the Wittig reaction do?

turns an aldedhyde/ketone into an alkene with another product of triphenylphosphine oxide

Wittig reaction (details)

Multistep reaction that involves the addition of a phosphonium ylide (deprotonated phosphonium salt) to an aldehyde/ketone to make an alkene

Reactants: aldehyde/ketone, phosphonium ylide

Products: alkene, triphenylphosphine oxide (Ph3P=O)

-C=O bond is converted to a C=C bond (carbonyl to alkene)

-intermediate: betaine and oxaphosphatane

P-O bond drives the reaction

-reaction is subject to steric hinderance (less hindered carbonyl carbons will have a higher yield)

-reaction occurs under mild conditions

Wittig reaction mechanism

1. anion carbon on ylide attacks the carbonyl carbon, one bond to oxygen break and electrons go to oxygen --> betaine

2. anion oxygen on betaine forms a bond to the positive phosphorus --> oxaphosphatane

3. Carbon oxygen bond breaks so oxygen forms a double bond to phosphorus, phosphorus carbon bond breaks to form the carbon alkene bond --> alkene + triphenylphosphine oxide

what is a phosphonium ylide?

a ylide with a negative carbon directly bonded to a positive phosphorus atom

What drives the Wittig reaction?

the strong P-O bond

Triphenylphosphine oxide structure/formula

Ph3P=O

You can get a phosphonium ylide by _____________ a phosphonium __________

You can get a phosphonium ylide by __deprotonating__ a phosphonium __salt__

Phosphonium ylide preparation reaction (details)

a phosphonium ylide can be prepared in a two step reaction using an alkyl halide (1° or 2° RX), triphenyl phosphine, and an n-butyl lithium (deprotonates the phosphonium salt)

-phosphonium salt intermediate (deprotonated by n-butyl lithium to get the ylide)

-alkyl halide is preffered to be 1° because the first step is an SN2 reaction

Phosphonium ylide preparation reaction mechanism

1. lone pair on phosphorus of triphenylphosphine bonds to the electrophilic alkyl halide carbon, halogen leaves --> phosphonium salt

2. phosphonium salt (carbon bonded to the phosphorus) is deprotonated by n-butyl lithium --> ylide +alkane

How do you determine which alkene stereoisomer is produced after the Wittig reaction

based on the reactant ylide

normal ylides: favor Z isomer

stabilized ylides: favor E isomer

normal vs stabilized ylide

normal ylide: carbon anion has two regular R groups bonded to it

stabilized ylide: carbon anion has electron withdrawing groups bonded to it (delocalizes charge which increases stability, can often be show by drawing a resonance structure)

Wittig reaction summary

1. Nucleophilic addition to make betaine

2. Ring closure to make oxaphophatane

3. Fragmentation to get the alkene and triphenylphosphine oxide

what does THP stand for?

tetrahydropryanyl

what is an enol?

an alcohol bonded to a double bond

what is an enol ether?

and ether oxygen bonded to a double bond

Furan

known structure

tetrahydrofuran

known structure

pyran

known structure

tetrahydropuran

known structure

THP Acetal structure

known structure

phenyl sulfonic acid pKa

-2

phenyl sulfonic acid structure

known structure

Reaction to form a THP acetal (details)

THP acetals can be made to act as a protecting groups for alcohols (primary or secondary alcohols)

-Reactants: primary or secondary alcohol, dihydropuran, phenyl sulfonic acid, H+ catalyst

-Products: THP acetal

-reverse reaction can occur in aqueous acid to regenerate the alcohol (acetal hydrolysis)

Reaction to form a THP acetal mechanism

1. double bond on dihydropuran bonds to proton from phenyl sulfonic acid --> oxonium cation (resonance stabilized) + conjugate base of phenyl sulfonic acid

2. alcohol attacks carbon of C=O double bond --> protonated THP acetal

3. conjugate base of phenyl sulfonic acid deprotonates the acetal --> THP acetal

use for THP acetals?

alcohol protecting groups

dihydropuran

known structure

What is an imine?

fucntion groups of a C=N double bond (also referred to as Schiff bases)

Reaction to form an imine (details)

Primary amines can undergo a condensation reaction(carbonyl oxygen comes off as water) with aldehydes/ketones to form an imine through a carbinol amine and iminium cation intermediates

-key intermediates: carbinol amine, iminium

-reaction occurs at a slightly acidic pH about 5

-reaction is reversible (reverse is imine hydrolysis in aqueous acid)

-reaction is pushed to completion through the removal of water

-acid catalyst is regenerated in the reaction

Reaction to form an imine mechanism

1. nitrogen attacks carbonyl carbon, one bond to oxygen breaks and electrons go to oxygen --> Zwitterion

2. ~H+ (protonation and deprotonation sequence) --> carbinol amine

3. alcohol on carbinol amine is protonated by the protonated amine --> oxonium cation + amine

4. nitrogen forms a double bond to the original carbonyl carbon, water molecule kicked off --> iminium cation + H2O

5. iminium cation deprotonated by an amine --> imine + protonated imine (regenerated acid catalyst)

why is the formation of an imine reversible?

amines are weak nucleophiles that can add reversibly in reactions

What would happen if a reaction to form an imine was too acidic?

the amine would be protonated so it would be unable to act as a nucleophile in the first step of the reaction (unable to react with the electrophilic carbonyl carbon)

What type of molecule is viatmin A?

aldehyde