Johns Hopkins University - Organic Chemistry Lab Exam 2 (Labs E-F, plus A-D from before)

Diels-Alder Reaction

A cycloaddition reaction between a diene and a dienophile to form a cyclic product with 1 new double bond

Cycloaddition reaction

1,4 addition of a 1,3 diene (conjugated diene) and an alkene (dienophile). forms a new 6-membered ring.

Cycloaddition/Diels-Alder new bonds

- 3 pi bonds break between the reacting diene/dienophile

-2 new sigma bonds and 1 new pi bond in the product

(sigma bonds between carbons 1 and 6, and 4 and 5)

(pi bond between carbons 2 and 3)

Reactants in Diels Alder

Diene (1,3-diene, conjugated) and a dienophile (alkene)

Characteristics of a Diels-Alder Reaction

1. Thermal cycloaddition rxn (initiated by heat)

2. Concerted rxn (bond breaking & forming occur in a single step)

3. 3 pi bonds break

4. 2 new C-C sigma bongs and 1 new pi bond formed

5. Forms new 6-membered rings

2 conformations of Dienes

s-cis (double bonds are cis) and s-trans (double bonds are trans)

ONLY S-CIS IS REACTIVE IN DIELS-ALDER

Reactivity of Dienes

Diene must be in s-cis conformation for Diels-Alder reaction to occur

- both ends of the conjugated diene must be closed to the pi bond of the dienophile for the Diels-Alder reaction to occur

Reactivity of Dienophiles

Electron withdrawing groups makes dienophiles more electrophilic --> more reactive

Least to Most reactive:

H2C=CH2 < H2C=CHZ < ZHC=CHZ

Stereospecificity of Dienophile

When a Diels-Alder reaction involves substituted dienophiles, the stereochemistry about the double bond in the dienophile is retained!

- cis-substituted dienophile produces cis-substituted cyclohexene (cis product - meso compounds)

- trans-substituted dienophile produces trans-substituted cyclohexene (trans product- enantiomers)

Variac

Variable voltage transformer, regulates heat transferred to heating mantle. plug under the fume hood.

Purpose of refluxing a reaction

To heat a reaction mixture at its boiling temperature (the boiling point of the solvent used in the reaction) to form the product, without losing any material inside the reaction flask.

Advantages of a reflux

- maintains a constant temperature in the reaction flask

- reaction is able to reach equilibrium with minimal evaporation of material inside the reaction flask

Cheletropic elimination

forms a conjugated molecule. pi bond and 2 sigma bonds break and 2 new pi bonds form

Cheletropic elimination advantages for Lab E

1. Non-hygroscopic solid (does not absorb moisture)

2. Not a flammability hazard

3. Excess 1,3-butadiene and SO2 are gases at room temp and are distilled out during reflux

Overall reaction for Lab E

1. Butadiene sulfone (3-sulfolene) --heat/xylenes--> s-cis-1,3-butadiene

2. s-cis-1,3-butadiene + Maleic anhydride --heat/xylenes--> 4-cyclohexene-cis-1,2-dicarboxylic anhydride

What is xylenes used for in Lab E?

refluxing solvent

Why can't we directly use s-cis-1,3-butadiene in Lab E?

Because it is a gas at room temp and hard to work with. So we use solid butadiene sulfone to generate s-cis-1,3-butadiene in situ so that it can immediately react with maleic anhydride in a Diels-Alder reaction

What happens to sulfur dioxide in Lab E?

the SO2 vapors will climb through the condenser as a white smoke and are distilled out during reflux

What is the purpose of the heating mantle?

to ensure efficient heat transfer. made of insulated fiberglass, supports the base of the RB flask

What kind of flask do we use in Lab E?

a 50 mL round bottom flask

Safety considerations for Lab E

- RB flask NOT on surface of stirrer - need mantle in between because otherwise the organic solvent would boil away, which would ruin the reflux and is a flammability hazard

- cords wrapped around metal bar so it is secure and doesn't flop around

- heating mantle plugged into VARIAC - if plugged into the regular outlet, the heat is unregulated and everything can evaporate, which is bad

- if mantle fiberglass fabric is cracked or the cord is frayed - do not use!

Where do we plug in the heating mantle?

The Variac! never into the regular outlet

Which direction does water flow in the condenser and where does it enter and leave?

Flows up the condenser. Cool water enters the bottom and leaves at the top.

CHWS

chilled water supply (bottom arm)

CHWR

chilled water return (top arm)

How does the water condenser work?

Once the solution reaches the boiling point of the solvent, the solvent vaporizes and vapors climb up the inner hollow tube of the condenser. Water flows up the outer jacket of the condenser. The water cools down the vapor, which causes the vapors to condense back in the reaction flask (forced it back down into the flask because of water in the outer jacket)

- no solvent lost! volume maintained through condensation/evaporation

Where do the vapors go in the condenser?

Up the inner hollow tube

Where does the water go in the condenser?

water flows up in the outer jacket of the condenser

Where do the gases formed in the reaction escape?

gases escape through the inner hollow tube and are vented through exhaust lines inside the fume hood

keep fume hood closed to prevent gases from escaping the hood

What do we put in the reaction flask for Lab E?

we put all of the reactants in at the beginning because we will first do an in situ synthesis, which will immediately be followed by a Diels-Alder reaction.

we add:

- 2.7g of butadiene sulfone

- 1.5g maleic anhydride

- 4 mL xylenes

Why do we need to turn off stirring to check for boiling?

stirring can create bubbles and mislead you to think the solution is boiling

What do we do after the solution is boiling?

remove the foil covering

What do we see climbing the condenser in Lab E?

solvent vapors

white smoke (SO2 vapors)

Make sure the condenser is always _____ to the touch

cold

What happens if the condenser is not cold to the touch?

This can be caused by attaching the CHWS and CHWR in the wrong place. Hot condenser means reflux is not happening and this could cause all the solvent to boil away, which is a flammability hazard.

Limiting reagent and excess reagent in Lab E

Limiting reagent = maleic anhydride

Excess reagents = 1,3-butadiene and SO2 (distilled out as gases during reflux)

How long is the reflux for Lab E?

30 mins

What do we do after refluxing the solution in Lab E?

cool to flask and then add 9mL xylenes to the RB flask with a pasteur pipette, then warm the flask in a warm water bath for 2 mins

Why do we add xylenes to the reaction flask after refluxing? What do we use to add the xylenes?

to dilute the mixture in the RB flask. add using a pasteur pipette

Why do we decant the supernatant fluid in Lab E?

To avoid impurities. a brown sludge can form, so decanting leaves this in the RB flask so that we can just have the supernatant in the beaker without the impurities

Why do we add petroleum ether in Lab E, how much do we add, and what do we use to add it?

We add 10mL of petroleum ether using a pasteur pipette in order to help the Diels-Alder product crash out of solution. The product is much more soluble in xylenes than in pet. ether, so we add low boiling pet. ether to help it precipitate.

What do we do to separate the DA product from the solvent in Lab E?

Vacuum filter - use spatula to scoop the caked product into the funnel. then after filtering, scoop it out of the funnel w a spatula

Vacuum filter paper in Lab E

DO NOT WET THE FILTER PAPER WITH H2O!!! the reaction was done in organic solvent, so we don't want to introduce an aqueous solvent

Appearance of Diels Alder product

product: 4-cyclohexene-cis-1,2-dicarboxylic anhydride

wet product: solid white, yellowish crystals

put onto watch glass to dry and take a tiny spatula's tip worth and put into a vial for IR spectroscopy

IR spectroscopy

used to detect functional groups present

IR absorptions

due to stretching and bending of covalent bonds in molecules

Regions in IR spectroscopy

Functional group (diagnostic region): determines the functional groups present

Fingerprint region: used for structure elucidation by spectral comparison

Bonds and frequency

Stronger bonds = higher frequency

lighter atoms = higher frequency

higher frequency = higher energy

What is Fisher esterification used for?

reliable method to synthesize esters on an industrial scale

Fisher esterification general reaction

carboyxlic acid + alcohol --acid catalyst--> ester + H2O

How do we push the esterification reaction in the forwards direction (since it's an equilibrium?)

can either:

- use an excess reactant (like in Lab F)

- remove water as it forms

Esters

RCOOR

- fruity odors

- used as flavoring agents, also used in perfume industry

General method for preparing esters

reflux mixture of carboxylic acid and an alcohol in the presence of an acid catalyst, like concentrated H2SO4 of HCl

- reflux

- extraction

- distillation

Overall reaction for Lab F

isopentyl alcohol (3-methyl-1-butanol) + glacial acetic acid --(conc. HCl)--> isopentyl acetate (banana oil) + H2O

Glacial acetic acid

the anhydrous form (no H2O) of acetic acid

- called glacial because it forms needle-shaped crystals when frozen

- excess reactant in the reaction (most economical)

- BP 118 degrees C

Glacial acetic acid hazards

Flammable (2), Health (3), Corrosive

Sulfuric acid hazards

Corrosive, Health (3)

Boiling stones

- use to avoid bumping during reflux, maintains even boiling

- never reuse boiling stones

- scoop them out with a spatula and depose of in biohazard box

Reaction flask used in Lab F

100 mL round bottom flask

What temperature is the reflux carried out at for Lab F?

117-118 degrees C, the boiling point of glacial acetic acid

How long is the reflux time for Lab F?

50 mins

What is the color of the solution after refluxing in Lab F?

Deep purple-red color

Size of sep funnel used in Lab F

125 mL sep funnel

What type of funnel do we use to pour the solution into the sep funnel?

pyrex funnel (long stem)

do NOT let boiling stones go into the funnel! will clog it!

Separation of layers in sep funnel after adding 50 mL water

- top layer = organic layer, contains glacial acetic acid solvent, excess isopentyl alcohol, regenerated acid catalyst, and of course the product isopentyl acetate

- bottom layer = aqueous layer, contains the water

Addition of NaHCO3 to sep funnel

- fizzing due to CO2 formation

- neutralizes leftover glacial acetic acid in solution

-

Addition of brine to sep funnel

begins drying process by draws out large amounts of H2O in organic layer

Top organic layer

-drain into 125 mL Erlenmeyer flask

- add anhydrous CaCl2 drying agent

Anhydrous CaCl2

drying agent, pulls out H2O

- add using a spatula until it no longer clumps together and is free flowing

Gravity filter

traps CaCl2 in filter paper and collected liquid isopentyl acetate in RB flask

Why do we do a simple distillation in Lab F?

- isopentyl acetate product may contain unreacted isopentyl alcohol

- we don't do a fractional distillation with a Vigreux column because that would cause us to lose a lot of product - instead, we do a simple distillation

-

Parts of a simple distillation

- 3-way distillation adapter

- 2 blue keck clips

- thermometer adapter

- vacuum adapter

- thermometer

- labeled vial for product

- 2 new boiling stones

Ring stands in the simple distillation

- 1 clamped around 25 mL RB flask

- 1 clamped around water condenser

Flask used for simple distillation

25 mL RB flask

3-way adapter arms connections

- side arm: water condenser

- bottom arm: neck of the RB flask

- top arm: thermometer and thermometer adapter

Blue keck clips

connect glass on glass joints

How many boiling stones go into the flask during simple distillation in Lab F?

2 boiling stones

Thermometer in simple distillation

- alcohol thermometer is poorly calibrated at room temp, so we collect over a bp range of 125-138 degrees C even though the lit bp of isopentyl acetate is 142 degrees C

- thermometer red bulb MUST BE COMPLETELY BELOW THE SIDE ARM OF THE 3 WAY ADAPTER!!!

Distillation in Lab F

- cover flask for 5 mins until reaches boil

- collect material between 125-138 degrees C

- vapor start condensing on thermometer bulb

- then, vapors go through water condenser and are cooled by the cold water and become a clear colorless liquid

Appearance of final product in Lab F

Final product = isopentyl acetate aka banana oil: clear, colorless liquid

Why don't we distill all of the liquid in the reaction flask?

leave 1-2 mL of liquid in RB - don't distillate to dryness because this will char the flask and make it very difficult to clean. creates pyrolytic tars!

Simple Distillation

- technique used to separate 2 or more liquids

- used to separate 2 or more liquids below 50 degrees C at 1 atm from nonvolatile impurities or another liquid that boils at least 25 degrees C higher than the first

- liquid is vaporized then recondensed back to a liquid (distillate) and collected in a receiving flask

Industry distillation

widely used in industry. separates oils into different fractions based on bp differences

Vacuum distillation

used for compounds that boil at too high a temp or decompose near their bp. under vacuum, can be distilled at temps lower than their atmospheric bp. use only for compounds with bp>200 degrees C

Fractional distillation

- use to separate compounds that are soluble in each other and boil at less than 25 degrees C from each other at 1 atm

- use Vigreux column with indentations - provides more surface area over which a number of separate liquid-vapor equilibria can occur

- efficiency = expressed by number of plates

- each cycle causes the vapors to become more enriched in the more volatile/low boiling liquid

Factors affecting boiling points

1. Size (molecular weight)

- larger = higher bp

2. Intermolecular interactions

- more/stronger interactions = higher bp

Boiling point

temperature at which the vapor pressure = external pressure

How much does the bp increase per additional carbon?

30-40 degrees C

Clausius-Clapeyron equation

an equation that displays the exponential relationship between vapor pressure and temperature

Normal boiling point

defined as temp at which a liquid's vapor pressure = 1 atm

more molecules vaporize at higher temps

Thermometer bulb position

COMPLETELY below the side arm of the 3-way adapter

read the thermometer when the material starts collecting, not when the solution starts boiling

When do we read the thermometer?

read when the material starts collecting, not when the solution starts boiling

Partition coefficient

K=Solubility of solute in organic layer/solubility of solute in aqueous layer

Excess reactant in Lab F

glacial acetic acid

Why do we add NaHCO3 in Lab F

adding NaHCO3 deprotonates the acetic acid, which is a carboxylic acid (pka=5, can be easily deprotonated), into sodium acetate. Sodium acetate is soluble in H2O, so it's drawn into the aqueous layer and we can remove it when we drain the bottom layer (and then we are just left with isopentyl acetate and maybe a little unreacted isopentyl alcohol). This reaction produces CO2, so must vent when shaking!!

In the Diels-Alder reaction, when we do a vacuum filtration, what do we not wet the filter paper with?

Water

The filtrate collected during the Diels-Alder reaction is disposed of into ____________________.

CHO non-halogenated container