CH220C Aldol Condensation

what are we studying in the adol condensation lab?

the synthesis of trans-p-anisalacetophenone via an aldol condensation rxn

what is an aldol reaction?

an addition rxn of an enol or enolate to a carbonyl compound such as aldehyde or ketone

what is the product of just the aldol reaction and what does this turn into, generally?

a beta-hydroxy carbonyl compound

it produces an alpha,beta-unsaturated compound

how is the enolate formed in the reaction?

the OH- grabs an alpha proton, forming a negative charge on the alpha carbon

does acetophenone or p-anisaldehyde have alpha hydrogens?

only acetophenone

the compound that has alpha hydrogens is _______________ and will be converted into _____________ by NaOH

nucleophilic, enolate

is an enolate resonance stabilized?

yes!

at elevated rxn Ts, why does an a,B-unsaturated compound form?

it is more energetically stable due to the creation of extended conjugation (pi-way, single-double-single-double, etc.)

do we need to preform the enolate? why/why not?

no

because only acetophenone has alpha carbons, so only one enolate is formed

what is the general rxn for the aldol condensation? *be able to draw out the complete mechanism*

acetophenone + p-anisaldehyde + NaOH + heat --> 3-hydroxy-3-(4-methyoxyphenyl)-1-phenylpropan-1-one --> trans-p-anisalacetophenone + H2O

describe the 6 steps of the procedure for the aldol condensation

1. add .2mL p-anisaldehyde, .2mL acetophenone, and 1mL ethanol to a 5mL conical vial w/ a small rice stirbar

2. add 3 drops of 50% NaOH soln

3. stir for 10 min until soln solidifies (takes <5 min) reaction is completed when stir bar can no longer rotate

4. while rxn is stirring, set up buchner filtration apparatus

5. filter solid product, rinse w/ cold ethanol

6. save the product for next week for mass MP, and IR

is the aldol condensation lab hard? how can you fail?

no! it is very simple and quick

you can fail if you add the wrong reactants

how do you know the rxn is complete?

the stir bar can no longer rotate

in general, how do you use the IR?

1. clean plate w/ isoproponal before and after

2. allow plate to air dry

3. inspect underside of press for contamination

4. turn press indicator until 1/2way green (if red, unscrew-anvil can crack)

rate of increase should be no more than _____________ for mel temp

2°C per min

what is the solvent for this reaction?

ethanol

aldol reactions are important ways to form new _____________________

carbon-carbon bonds

what is an aldol?

a molecule that contains both aldehyde and alcohol functional groups

what is the pka of the protons of the alpha carbon?

about 18-20 pka (pretty acidic for a C = C can be deprotonated to become nucleophilic)

is NaOH capable of deprotonating an alpha carbon w/ protons?

yes

why are the H's on the alpha carbon so acidic?

because the conjugate base is resonance stabilized

how are new C-C bonds formed in aldol condensations?

nucleophilic carbons (w/ formal negative charges) can attack a carbonyl carbon (electrophilic)

what protonates the negative oxygen intermediate?

water

how can a dehydration rxn occur?

there are still 2 acidic Hs on the molecule to grab to form a more stable double bond

is the final product cis or trans, why?

trans- more stable isomer

Could the enolate ion from acetophenone add to another acetophenone molecule?

yes

why isn't the product formed by the rxn of the enolate w/ another molecule of acetophenone the major product?

because the addition to aldehydes is faster than to ketones, so p-ansialdehyde is the preferred electrophile

the other rxn is much slower

What is the Cannizzaro Reaction?

side reaction when 2 molecules of anisaldehyde reacts with NaOH to form a carboxylic acid on one aldehyde an alcohol on the other

what is the problem with mixed aldol reactions?

there are multiple potential enolates and electrophilic carbonyls, so multiple products are made that are hard to separate

what are 2 ways to solve the problem of mixed aldol rxns?

1. prepare enolate on its own before (NaOH - not strong enough, equilibirum to left) (LDA- strong enough)

2. only use one aldol w/ alpha protons, have one aldol be a better electrophile (WE ARE DOING THIS)

why are aldehydes better electrophiles than ketones?

less steric hindrance

what data are we collecting in the aldol condensation?

MP, % yield, IR

is the final product a solid?

yes

what is the main source of product loss in the aldol rxn?

transfer issues because it is microscale (very small)

what are we looking for on the IR?

carbonyl peak

no methyl peak

no OH peak

what are the symptoms, prevention, and first aid for the ingestion of methanol?

S: inebriation, drowsiness, coughing, headache, dullness, weakness, vertigo, dizziness, nausea, vomiting, diarrhea, blindness

P: do not eat or drink in lab

FA: if vomiting occurs, keep head lower than hips, get medical attention if needed

why do we add 100% alcohol?

to prevent the reaction from reversing (we add it in excess)

why do we add sodium bicarbonate into ice water?

add the sodium bicarbonate w ice water bc is an exothermic rxn (i think)

methanol

possible mutagen

sulfuric acid solution

known carcinogen

sodium sulfate

carcinogen, mutagen

diethyl ether

Possible mutagen

what makes a-hydrogen more acidic

stabilization through inductive effects and resonance

why can we use NaOH to perform reaction rather than needed a strong base like LDA

Because steric and electronic effects. Aldehydes are better electrophiles than ketones bc steric hinderance

What are two ways in which the a-carbon atoms can become nucleophilic

- deprotonation to form enolate ion

- keto–enol equilibration, called tautomerization, to give an enol

What is a mixed or crossed-aldol condensation

two different carbonyl compounds are the reactants