Lab G: Grignard Reaction Flashcards
waste disposal procedure:
aqueous waste (from extraction) –>
waste from RB flask containing any reacted Mg –>
anhydrous MgSO4 –>
filtrate (after vacuum filtration) –>
HOODS -
aqueous waste (from extraction) –> “grignard aqueous waste” container (should NOT be poured down the sink)
waste from RB flask containing any reacted Mg –> brough to 186 for cleanup (should NOT be poured down sink)
anhydrous MgSO4 –> “Anhy. MgSO4 waste” container (NOT in biohazard waste box)
filtrate (after vacuum filtration) –> “ether, hexanes, acetone waste” container
HOODS - should be NO paper towels inside or around sink area; hoods should be lowered down ALL THE WAY
Why is it necessary for a grignard reaction to be under ANHYDROUS conditions?
grignard reagents serve as a carbanion, which means they are also very STRONG BASES
–> thus they will react more quickly with water, alcohol, and carboxylic acids (aka proton sources) than their intended carbonyl targets
–> thus to make sure the grignard reagent reacts with the carbonyl compound and not any proton sources, water is not allowed in the lab reaction
for this lab specifically, what are we using to ensure anhydrous conditions for the reaction?
- anhydrous diethyl ether
- drying tubes - with indicating drierite inside
(making sure to clean your glassware the week before so that it dries completely)
the grignard reaction is an example of what type of ____ forming reaction?
Carbon-Carbon bond forming reaction
what is the first step of a grignard reaction?
step 1. the insertion of Mg into a C-X (halogen) bond –> forms an organometallic compound
describe the bond polarity of a carbon-metal bond (in this case C-Mg bond) and the significance of this
the C-Mg bond is relatively ionic –> reverses the polarity of the Carbon from partially positive to partially negative since metals are even less electronegative than Carbons
–> this makes carbon a very STRONG NUCLEOPHILE that can undergo nucleophilic addition reaction into a C=O compound to form a new C-C bond
who discovered the grignard reaction and what year?
Victor Grignard 1912
describe the grignard reaction for this lab specifically
- preparing phenyl magnesium bromide
- reaction phenyl magnesium bromide + methyl benzoate –> triphenylmethanol
how is a grignard reagent formed?
grignard reagent formed by the reaction of an alkyl or aryl halide on a CLEAN magnesium surface
in general it is easiet to form a grignard reagent from what?
in general it is easiet to form a grignard reagent from AKLYL OR ARYL IODIDES
(in second place is bromides, and last is chlorides)
how are bromides commonly used for forming grignard reagents?
bromides are used to balance the COST of the starting material with the EASE of the reaction
why do we need to grind our magnesium turnings before use?
since the grignard reaction (step 1. preparation of grignard reagent) happens on the SURFACE of Mg, we need to grind the Mg turnings to get rid of the magnesium oxide coating on the top of the Mg turnings –> this exposes a clean Mg surface such that the reaction can take place
- we do NOT want to form a powder with the Mg turnings (it is sufficient to break it up just enough to expose a fresh Mg surface without the magnesium oxide MgO coating)
what are grignard reagents synthesized in and why?
Grignard reagents are synthesized in ANHYDROUS DIETHYL ETHER
the anhydrous diethyl ether
1. serves as the solvent
2. the electron pairs on the ether coordinate with the Mg metal and help to SOLUBILIZE the reagent
3. the high vapor pressure of diethyl ether will exclude oxygen from our reaction (which is beneficial since grignard reagents can react with oxygen)
what is another solvent that is used in the formation of grignard reagents?
tetrahydrofuran
- frequently used when HIGHER temps are needed to initiate the reactions
why is it important to initiate the reaction and then GRADUALLY add the rest of the substrate?
the grignard reagent formation reaction is AUTOCATALYTIC: meaning that it is difficult to initiate the reaction, but after it is initiated it generates a lot of HEAT and begins to process very quickly
–> if there is too much substrate present (aka not added gradually into the reaction flask), the reaction can begin to generate enough solvent to vaporize more solvent that the reflux condenser can condense –> and thus build up more pressure that can escape from the condenser
(aka the reacton solvent is vaporizing faster than the reflux condenser can condense back down into the reaction flask, which causes more pressure to form than pressure can be let out through the condenser –> ultimately leading to an EXPLOSION)
is the formation of a grignard reagent autocatalytic?
YES
it is autocatalytic: it is hard to initiate at first, but after it is initiated, the reaction generates a lot of heat and proceeds very quickly
for our lab reaction, how will we control the rate of substrate being added so that an explosion does not occur?
we will add bromobenzene at a rate that will maintain a gentle reflux
- a steady drip from the reflux condenser
very important to make sure that your grignard reaction has initiated before going on
what is another side reaction that can occur?
a final side reaction that can occur is the FORMATION OF A DIMER
- in our reaction, it is biphenyl
how do we prevent the formation of a dimer in our reaction? (what is the possible dimer being formed)
we are trying to prevent the formation of BIPHENYL by diluting the reaction (after it has spontaneously initiated) before adding the remaining bromobenzene from the separatory funnel
- we add the additional anhydrous diethyl ether to dilute the reaction only AFTER the reaction has spontaneously initiated since it is hard to initiate a grignard reaction under dilute conditions since it reduces the concentation of bromobenzene near the Mg surface
why do we add the additional anhydrous diethyl ether before adding the rest of the bromobenzene from the separatory funnel?
we add the additional anhydrous diethyl ether to dilute the reaction to try to prevent the formation of a dimer (biphenyl) which is a possible side reaction
why do we add the additional anhydrous diethyl ether AFTER the reaction has spontaneously initiated?
since it is difficult for a grignard reaction to initiate in dilute conditions, we add the additional diethyl ether AFTERWARDS to solve this issue while also diluting the solution to prevent dimer formation
explain the reaction between phenyl magnesium bromide + methyl benzoate –> triphenylmethanol (intermediates, relative stability) and draw the mechanism
the intermediate produced in the reaction is BENZOPHENONE (just two phenyl groups and a ketone in between)
which is from the FIRST addition of the grignard reagent to the carbonyl compound
- however, since ketones are more reactive than esters in nucleophilic addition reactions, the grignard reagent (phenyl magnesium bromide) will NOT react with the remaining methyl benzoate (ester) and instead do the SECOND addition onto benzophenone (ketone) to produce triphenylmethanol
- hence there are 2 equivalents of the grignard reagent for 1 ester to form a tertiory alcohol
- also, we cannot form any ketone from a grignard reaction with an ester since the ketone will just react again with the grignard reagent to produce an alcohol; even if only 1 euivalent of grignard reagent was used, we would just get a bad yield of the ketone product
- however, we could have chosen to synthesize triphenylmethanol from phenyl grignard and benzophenon (ketone)
when can we no longer need to be concerned about the anhydrous reaction conditions?
after the grignard reagant has reacted with the carbonyl compound
- Once the Grignard reagent has reacted, we have produced the magnesium salt of an alcohol.
Because the reaction with the air-sensitive Grignard is now complete, we no longer have to be
concerned about anhydrous conditions
how and why do we quench the reaction after the grignard reagent reacted with the carbonyl compound?
we quench the reaction by pouring it onto ice-cold dilute SULFURIC ACID (H2SO4) since we no longer need to worry about keeping the reaction in anhydrous conditions
- we add the H2SO4 to protonate the magnesium salt of the alcohol produced from the reaction to ultimately form the final product triphenylmethanol
why do we add H2SO4? (sulfuric acid)
- H2SO4 provides a proton to the alkoxy salt to give triphenylmethanol
- reacts with any unreacted magnesium metal
- convert the Mg(OH)2 salts which are insoluble in water into soluble MgSO4 salts
upon loss of water, what can triphenylmethanol form?
it can form the relatively stable triphenylmethyl carbocation (aka just without the OH group and a missing H)
after the reaction is complete and quenched, what does the reaction mixture contain and what needs to be done?
after the reaction is complete and quenched, the reaction needs to be PURIFIED (extraction)
- at this point, the reaction mixture contains triphenylmethanol and Mg salts, or biphenyl, benzene, and unreacted starting materials
describe the extraction setup (what is in the organic vs aqueous layers) on how triphenylmethanol is purified
aqueous layer: the Mg salts
organic layer: the remaining compounds (triphenylmethanol, biphenyl, benzene, unreacted starting materials)
1. Mg salts is drained out of the sep. funnel
2. the sep.funnel is washed with additional water
3. organic layer is washed with NaHCO3 to neutralize the excess acid
4. brine is added to begin the drying process
what is the drying agent pellets used after extraction in this lab?
anhydrous MgSO4 drying agent pellets
why is hexanes and simple distillation used in this lab?
even after drying the remaining organic mixture with anhydrous MgSO4 pellets, the organic layer will contains unreacted starting materials and the product triphenylmethanol
–> to separate triphenylmethanol, hexanes and simple distillation helps remove the diethyl ether and triphenylmethanol should “crash out of solution” or aka crystallize our while the rest of the unwanted materials remain in solution
- this works since triphenylmethanol is much less soluble in hexanes than the remainder of the other materials
–> vacuum filtration is performed on the triphenylmethanol crystals that crashed out of solution by adding hexanes to purify the crystals –> final product
what is the difference between hexanes and hexane?
hexanes is a MIXTURE of hexane isomers
- they have the same chemical formula but DIFFERENT STRUCTUAL FORMULA
- hexanes is different from n-hexane (pure)
what are the components that go into the grignard REFLUX SETUP?
- 125mL sep funnel
- CLAISEN ADAPTER
- 2 thermometer adapters
- 2 drying tubes
- stir bar
- 250mL RB flask
- 2 blue keck clips
what is the function of the claisen adaptor? (straight arm vs bent arm)
the claisen adaptor essentially converts one neck into 2 necks
- striaght arm: condenser
- bent arm: separatory funnel
why are thermometer adaptors used in the grignard reflux setup?
thermometer adaptors are used to SUPPORT the DRYING TUBES
describe the drying tubes (what is inside, their individual functions) and its function
the 2 drying tubes are made of glass and packed with ANHYDROUS CALCIUM SULFATE CaSO4 as a drying agent mixed with COBALT CHLORIDE CoCl2
- purpose of using anhydrous calcium sulfate is to keep moisture (aka water) away from the reaction system
- purpose of using cobalt chloride to serve as an INDICATOR (cobalt chloride is blue when it is dry and has no moisture, but when it absorbs moisture, it changes the pink color)
–> that way you know when to replace the drying tubes
- the kimwipe tissues at the top of the drying tubes are used to prevent the drying agent pellets from slipping out of the tubes
the drying tubes…
1. help equalize pressure
2. prevent atmospheric moisture from entering the system via the condenser (aka allows the reaction flask to be open to the atmosphere so that gas pressure does not build up)
what is used to grind the Mg turnings?
mortar + pestle
why is it hard to initiate grignard reaction?
Mg turnings have a Mg oxide (MgO) coating on the surface and the surface of the Mg turnings is where the grignard reaction occurs, so with the MgO coating on, it is difficult for the reaction to initiate/start
claisen adaptor, what sits in the straight arm vs bent arm and why (safety precaution)
straight arm: condenser
bent arm: sep.funnel
the sep. funnel sits in the bent arm to SLOW DOWN the rate of the addition of bromobenzene (aka the solute in this reaction) into the reaction RB flask (as we talked about, if the solute is added too quickly or too much in the reaction flask, the pressure of the system will increase and could cause an explosion which is a safety hazard)
- if the sep funnel was in the straight arm of the claisen adaptor, you would not be able to control the rate of addition of bromobenzene into the RB flask - it would be added too fast
sep. funnel stopcock position at the beginning of the reflux setup?
HORIZONTAL - CLOSED TO DRAIN position
where do the 2 blue keck clips go ont he reflux setup?
- connecting the sep funnel with claisen adaptor neck
- connecting the condenser with claisen adaptor neck
safety precautions of the grignard reflux setup (3)
- bent arm of claisen adaptor holds the sep. funnel and not the other way around
- the sep. funnel stopcock is set to CLOSED TO DRAIN in the beginning (aka before bromobenzene is added)
- the hot plate placed under the RB flask is used ONLY for STIRRING (no heat)
why do we need to be sure to keep our solvents (anhydrous diethyl ether and bromobenzene) covered?
we want the reaction to be under ANHYDROUS CONDITIONS –> need to cover them so no atmospheric moisture enters them
what is the most commonly used reagent for grignard reactions?
anhydrous diethyl ether
why is anhydrous diethyl ether used as the solvent for grignard reactions?
- grignard reagents can react with oxygen to form hydroperoxides
- to prevent this, we use Et2O since the vapors of this highly volatile Et2O solvent essentially forms a “vapor cloud” surrounding the reaction RB mixture –> which prevents oxygen from reaching the reaction mixture - it has been found experimentally that ether molecules can coordinate and thus help stabilize the grignard reagent in solution
what is the boiling point and flash point of Et2O ?
boiling point: 35C
very LOW flash point: -45C
==> volatile solvent (vapors) and highly flammable
what is the breakdown of the 50mL anhydrous Et2O? (4 increments)
- 10mL added into RB flask with the Mg turnings
- 15mL added to the sep funnel that will have bromobenzene
- 15mL added from the top of the condenser
- 10mL added into the sep funnel with methyl benzoate (for the 2nd reflux)
how many clamps are in the reflux grignard setup?
1 clamp only around the RB flask neck
why does the sep. funnel stopcock have to be in horizontal CLOSED TO DRAIN position before bromobenzene is added?
if the stopcock is in vertical open to drain position, then all of the bromobenzene will immediately and all at once flow into the reaction RB flask and react with the Mg turnings in there –> the reaction between Mg turnings and bromobenzene is very EXOTHERMIC (aka produces a lot of heat) and can potentially vaporize all of the Et2O solvent and lead to an explosion
what happens when you add iodine into the RB solution?
the solution will instantly change from clear –> DARK BROWN!
describe the color changes that occur during the 1st grignard reflux
dark brown –> light brown –> dark yellow –> light yellow –> gray
what do you do/check for after the solution turns gray color
turn off the stirring of the hot plate to check if the bubbles formed in solution are due to the solution spontaneously refluxing (aka generated from the Mg turnings and not from the stirring)
–> at this point, we have formed our grignard reagent phenyl magnesium bromide in solution inside the RB flask
what do you do after the grignard reagent phenyl magnesium bromide has been formed?
add 15mL of anhydrous Et2O from the top of the condenser to DILUTE the solution to reduce the rate of formation of the BIPHENYL DIMER which is a potential byproduct of the reaction between phenyl magnesium bromide and bromobenzene
- also you want to slowly add bromobenzene from the sep. funnel to prevent the bromobenzene from reacting with the phenyl magnesium bromide in the RB flask and forming the biphenyl dimer
describe the difference between the 2 refluxes
first reflux is for the formation of grignard reagent phenyl magnesium bromide
second reflux is for the reaction between phenyl magnesium bromide and methyl benzoate to form the final product triphenylmethanol
how does the color of solution change in the 2nd reflux?
methyl benzoate reflux reaction (aka 2nd reflux) - color chnages from dark brown (from the iodine addition btw) to a red color
what do you do after each of the refluxes?
unplug the heating mantle and place the RB flask in an ice-water bath for it to cool
- you unplug the heating mantle so that there’s no residual heat that prevents the solution from cooling
what has formed in the solution after the 2nd reflux? what do you do after the 2nd reflux?
after the 2nd reflux, we have successfully formed the magnesium salt of triphenylmethanol in diethyl ether and water insoluble magnesium salts (ie. magnesium hydroxide Mg(OH)2)
and now need to do the work up of the solution
why is dilute sulfuric acid used after the 2nd reflux?
- protonate the magnesium salt of triphenylmethanol to form triphenylmethanol
- convert the water INSOLUBLE Mg salts (ie. Mg(OH)2) –> water SOLUBLE Mg salts (Mg sulfate MgSO4)
- this reaction is very exothermic –> use ICE - convert any remaining Mg turnings –> Mg sulfate MgSO4
why do you use dilute sulfuric acid to prepare for extraction in the next step afterwards?
sulfuric acid basically turns all of the insoluble magnesium salts and Mg turnings (both of which are water-insoluble) into water-soluble magnesium salts like MgSO4 so that when you do the extraction with the sep funnel in the next step, the main thing left in the organic layer of the sep funnel is just the desired product triphenylmethanol and everything else is in the aqueous layer (makes extraction easier)
what happens when you add H2SO4 into the RB flask and swirl it? why is there there foaming and occurring?
any unreacted Mg turnings will react with H2SO4 to form Mg sulfate MgSO4 and the byproduct of hydrogen gas
Mg+H2SO4 –> MgSO4 + H2(g)
- the formation of the byproduct hydrogen gas from this reaction is what causes the foaming of the solution you see
describe the separation of phases and their colors in the erlernmeyer flask on the hot plate after adding H2SO4 and diethyl ether (NOT anhydrous)
top layer: LIGHT YELLOW organic layer with triphenylmethanol + diethyl ether
(product is in the top organic layer)
bottom layer: MILKY WHITE aqueous layer with water + Mg salts (water soluble)
what is the density of diethyl ether?
0.706g/mL
why is the bottom aqueous layer in the erlenmeyer flask milky white?
it is milky white due to the presence of magnesium salts
what happens to the color of the bottom aqueous layer of the erlenmeyer flask after adding concentrated H2SO4?
the bottom aqueous layer loses its milky white color due to the magnesium salts reacting with the sulfuric acid to form MgSO4
- you will see a lot of foaming and vigorous bubbling due to the formation of the hydrogen gas byproduct
what is added into the sep. funnel in order for extraction? (3)
- H2O - to draw out salts into the aqueous phase (no need to vent) –> drain aqueous layer into grignard aqueous waste beaker
- saturated NaHCO3 - to neutralize the excess sulfuric acid in the aqueous layer (need to VENT) –> drain aqueous layer into same beaker
- brine - to start the drying process –> drain aqueous layer
- drain and collect the organic layer (diethyl ether layer) –> add anhydrous MgSO4 drying agent pellets (to finish the drying process) –> gravity filtration
why do we use simple distillation?
use simple distillation to separate our product triphenylmethanol from the solvent diethyl ether
why do we use hexanes in gravity filtration in terms of simple distillation in the following step?
hexanes has a much higher boiling point (69C) than diethyl ether (35C) so Et2O will be distilled out first during simple distillation, thus leaving only triphenylmethanol and hexanes in the RB flask solution
–> after Et2O has been distilled out, the product crystals can crash out of solution (triphenylmethanol crystal dance) and thus we get our final product pure crystals
how long do you carry out the simple distillation for?
when the solvent level reaches approximately 1cm below from the sharpie mark made earlier on the RB flask –> then stop
what happens after simple distillation (distilling out the Et2O) and as the solution in the RB flask begins to cool? aka triphenylmethanol crystal dance
as the solution begins to cool (after distilling out the diethyl ether), you will see the triphenylmethanol crystals begin to crash out of the solution (which is now just hexanes) since the product has a much lower solubility in hexanes compared to in diethyl ether –> the triphenylmethanol crystal dance
what is the overall procedure of this grignard lab?
- reflux #1
2.reflux #2 - add H2SO4 –> extraction
- gravity filtration: with hexanes
- simple distillation
- vacuum filtration
–> after extraction, you are left with the organic layer of triphenylmethanol + diethyl ether (?)
–> after gravity filtration, the RB flask will contain your product triphenylmethanol + diethyl ether + hexanes
–> after simple distillation, the RB flask will contain triphenylmethanol + hexanes
–> after vacuum filtration, you will only be left with your pure product crystals triphenylmethanol
for the vacuum filtration done of the triphenylmethanol crystals, do we wet the filter paper with water?
NO because the product is in hexanes –> rinse the RB flask with hexanes as well (NOT water)
what do the pure and final triphenylmethanol crystals look like?
fine, light-yellow colored crystals
how do we mark the RB flask with a sharpie when we add the hexanes?
we mark the RB flask at where the level of hexanes are
what is different about the grignard lab gravity filtration setup vs the previous gravity filtration setups we have done?
the grignard gravity filtration requires you to first add hexanes into the RB flask that you are gravity filtering INTO
–> after gravity filtration, the RB flask will contain your product triphenylmethanol + diethyl ether + hexanes
–> after simple distillation, the RB flask will contain triphenylmethanol + hexanes
–> after vacuum filtration, you will only be left with your pure product crystals triphenylmethanol
who discovered the grignard reagent?
victor grignard - 1912 novel prize –> grately advanced the progress of organic chemistry
what do grignard reagents do?
the grignard reaction forms new C-C bonds
- turns a C-X (halogen) bond into a good nucleophile
- grignard reagents are extremely strong bases –> violently react with water, alcohols, acids to form an alkane
what are the electronegativities of C, Br, and Mg
C - 2.55
Br - 2.96
Mg - 1.31
–> C-Mg bond makes C with the partial negative charge –> C is the nucleophile
what are the functions of adding iodine to the solution during the first reflux?
- indicator - color of I2 fades as Mg is activated
- activator - chemically cleans the oxide layer on the surface of the Mg turnings to expose fresh Mg surface to react with bromobenzene
describe how refluxing a reaction works
- reaction occurs at the BOILING POINT of the solvent
- condenser prevents loss of solvent
- water flows UP the condenser (CHWS - bottom; CHWR - top of condenser)
- boiling stones/stir bar prevent bumping
- open at the top so you are not heating a closed system
how can you avoid the formation of biphenyl dimer (an impurity)?
- add bromobenzene SLOWLY so that it reacts with the Mg turnings and is not present in a large enough concentration to react with any previously formed grignard reagent
- dilute the solution (aka add additional diethyl ether) to reduce the rate of dimer formation (REMEMBER that any additional diethyl ether can be added only AFTER the reaction has been INITIATED)
- using LESS heat as possible to avoid formation (since the formation reaction requires heat)
what is the reaction between Mg turnings and sulfuric acid H2SO4?
Mg(s) + H2SO4(aq) –> MgSO4(aq) + H2(g)
what are the 2 layers in extraction and what are contained in them?
top organic (ether) layer: triphenylmethanol (ether-soluble)
bottom aqueous layer: MgSO4 + MgBr2 + H2SO4 + H2O (water-soluble magnesium salts)
anhydrous MgSO4 reacts with water to form what
anhydrous MgSO4 + H2O –> hexahydrate (a clumpy solid)
MgSO4 will not entirely remove the water layer –> instead, it binds with the water present in the organic solvent
