CH220C Aldol Condensation & Fischer Esterification

what are we studying in the fischer lab?

Fischer Esterification

what is generally happening in our Fischer Esterification?

a carboxylic acid is converted to an ester and water (byproduct) in the presence of an acid catalyst

how is water a problem in this experiment?

water is nucleophilic and can be added back into the compound and hydrolyze the newly formed ester to regenerate the starting carboxylic acid

how is the water issue circumvented?

the experiment is run in excess alcohol to drive the rxn towards the products

What is the general reaction for the Fischer experiment? *be able to draw out the complete mechanism*

benzoic acid + CH3OH (methanol) + (in H2SO4) --> Methyl Benzoate + H2O

what is the purpose of sulfuric acid?

it acts as an acid catalyst to protonate the carbonyl oxygen of benzoic acid to make the carbonyl carbon more electrophilic

what data are we collecting in the Fischer experiment?

IR, GC, % yield

what indentation in the aluminum block should you use?

the one that fits the round-bottom flask best

what are 3 things to remember about using the condenser water hoses?

1. use the metal pins
2. keep water pressure low
3. water in at bottom, water out at top

what are the first 6 steps of the procedure (through removing soln from heat)?

1. place 25mL distilled water in a 150mL beaker in an ice-water bath. In the ice-bath, place 1mL 6M NaOH in a test tube, and 10mL saturated sodium bicarbonate in a test tube
2. add 15mL 1M benzoic acid in the methanol soln to the 50mL round-bottom flask w/ the rice stir bar
3. add .5mL concentrated sulfuric acid to the round-bottom flask; attached west condenser; attach water lines
4. heat the round-bottom flask in heating block, set hotplate to ~220°C
5. after 30 min of refluxing, the rxn is complete (start timer once condensation is observed)
6. remove round-bottom flask from hotplate and pour into 150mL beaker w/ 25mL water

What is refluxing?

Refluxing is the boiling of a solution while continually condensing the vapor by cooling it and returning the liquid to the reaction flask

what is the point of refluxing?

to heat a soln in a controlled manner @ a constant T

after the sulfuric acid reacts with benzoic acid, what does the compound look like?

the carbonyl oxygen of the benzoic acid has been protonated (has a + charge)

does this compound have resonance?

yes! the positive charge is shared between the oxygen and the carbonyl carbon, making it more electrophilic

what is the nucleophile in this rxn?

the methanol

what are the final 6 steps of the procedure?

7. cool the soln in an ice-water bath for 5 min to ensure soln is below room T
8. add 1mL NaOH to the cooled soln, then roughly half of the saturated sodium bicarbonate, test the pH, cont. adding sodium bicarbonate 1mL @ a time til pH = 7, transfer neutralized soln to sep. funnel
9. add 15mL diethyl ether to the sep. funnel & extract the organic (non-aqueous) phase; drain the aqueous layer, set aside
10. wash organic layer w/ 15mL saturated sodium chloride soln, isolate organic layer, pour aqueous layers down the sink once analysis is completed
11. add several spatulas of sodium sulfate to product to dry it, shoot 1 uL of sample on GC and identify ester by comparing retention time to standard
12. decant liquid from sodium sulfate, follow instructions of TA to remove left-over diethyl ether. once pure product isolated, determine % yield and take IR

why are NaOH and sodium bicarbonate in an ice-bath before being adding?

because neutralization/ acid-base reactions are highly exothermic

Why is it important to neutralize the reaction mixture during the workup?

It ensures that the ester is uncharged and therefore insoluble in water so that the product can be filtered

what is the biggest safety concern in the Fischer lab?

concentrated sulfuric acid

what should you do when handling sulfuric acid?

handle carefully and change gloves immediately after

what should you be careful about when using the GC?

be careful w/ fragile needles, no gloves, don't touch GC or computer power button, don't logout of computer, be patient- spectra will print automatically

what is an ester? *be able to draw one*

derived from an oxoacid where at least one hydroxyl group (-OH) is replaced by an alkoxy group (-O-)

what are some uses for esters in real life?

fragrances, essential oils, pheromones, solvents, synthetic lubricants

what ° alcohols are needed for Fischer Esterification and why?

1° or 2° bc 3° alcohols are prone to elimination

what is the solvent in our rxn?

methanol (the reactant and the solvent so we have 2 uses out of having excess of it)

what are typical rxn times?

1-10 hrs at 60-110°C

will a carboxylic acid like benzoic acid react with methanol alone?

no, we need to make one of the reactants stronger to lower activation E

how do we lower the activation E?

using acidic conditions, which protonates the O of the carbonyl, making the carbonyl carbon more electrophilic (O pulls away more e- density)

what are three things we need to deal w/ to prevent product loss? how?

1. proton source- needs to be strong
2. equilibrium- adding excess reactant to drive rxn to the right
3. no products @ the start (H2O)- pure methanol

what is our proton source and why is it important that it is strong?

so it completely dissociates, so when a water molecule it forms, it reacts with it to form H3O+, removing H2O, driving reaction forward

why does our solvent have to be 100% pure methanol?

so there is no H2O present which is a product which drives our reaction towards the reactants according to le-chatlier's principle

explain using the equation for Keq why adding excess reactant drives the rxn forward

if Keq = 4 which is = to [products]/[reactants], if we add more reactants and 4 is a constant, then to keep 4 constant, the products increases = we make more products!

how do you calculate the expected product yield using keq?

Keq = [H2O][Ester] / [Acid][Alcohol] ~ 4 (water and ester will be equal)
Keq = x^2 / [1-x][1-x]
4 = x^2 / (1-x)^2
2 = x/ (1-x)
X = ⅔ ~ 67%

if we double our methanol, what is expected % yield? what if we triple?

2x = 85%
3x = 91%

why is having water at the start of the rxn a problem?

it is a product so more products drives the rxn towards the reactants

what should you do if exposed to sulfuric acid?

rinse in water for 15 min

what is the largest source of product loss for % yield?

liquid-liquid washes (need good technique!)

what is good % yield?

65%

what are we looking for on the IR?

presence of small peak in C-H stretch (for methyl group in ester)

absence of OH peak

can you do the GC before getting rid of the either?

yes! and you should so it is diluted and the peaks aren't too big

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