Welcome to Chem 225 Dr. Guangli Yang [email protected], [email protected] Office hour: Friday 3:00-4:00pm @ Rockefeller Research Laboratory.

Welcome to Chem 225 Dr. Guangli Yang

[email protected], 212-639-6748

Office hour: Friday 3:00-4:00pm @ Rockefeller Research Laboratory Rm 1327 67 str. between York and 1st Ave

All course information are available online via Blackboard ( full lab manual and course slides etc.)You need to register for RC225 separately.

Course Description and Grade Assignment

Expt 1 Expt 2 Expt 3 Expt 4 Expt 5 Eval. RC.exam Total

150 100 50 125 290 35 250 1000

 Total Points =715(Exp 1 – 5) + 35 (TA Evaluation) + 250 (Lab RC) 250 = 2 recitation exams (230 pt) + 5 quizzes (20 pt) Recitation attendance is Mandatory. Penalty for Late Lab reports.

Lab Safety

Safety Goggles must be worn at all time in the lab. Better to wear gloves. No eating and drinking in the lab. Lab Coats or inflammable clothes, no open toed shoes. PAY ATTENTION to where you put your chemical waste!

How to get good grade of this course• Planning 1. Attend the RC and view the lab manual before you walk into

the lab. Take good note in the RC and review them when planning each experiment.

2. The pre-laboratory assignment for each experiment must be completed before coming to lab.

• Laboratory Notebook 1. The preliminary write-up must be in your notebook before

you begin the experiment.(list of hazards and toxicities of compounds, glassware needed)

2. All data must be recorded at the time they are observed or obtained. (including weights, bp, mp, observations of physical changes, results and conclusions)

Garbage Disposal

Blue Bins

For regular garbage only.NO GLOVES!!!

Red Bins

For sharp materials only.Broken glass, pipettes,melting point tubes etc.NO GLOVES!!!

Waste Disposal

Biohazard Box

Put your gloves hereTHANK YOU

Chemical waste tray

Deposit ALL Organic waste in the assigned Bottle.DO NOT discard any wastedown the drain.

Emergency !

Emergency Shower

Eye Wash.Note: Contact Lenses should NOT be worn in the lab

Org. 2 Laboratory

exp.1-3work in pairs.exp. 4 and 5work individually.

EXPT 1: A MULTI-STEP SYNTHETIC SEQUENCE

This is a five-step experiment. It will take 3 lab period time to finish.

Step 1. Benzoin Condensation

H

OKCN/H2O

EtOH, reflux

O OH

Benzoin

Step 2. Reduction

NaBH4, EtOHOHHO

+

OHHO

Hydrobenzoin+/- mixture meso isomer

Step 3. Oxidation

O O

Benzil

Step 4. AldolCondensation

Ph Ph

O

HO

O

Ph Ph

Ph Ph

Step 5Diels-Alder reaction

MeO2C CO2Me

heat

Ph

Ph

Ph

Ph

CO2Me

CO2Me

Step 1: SYNTHESIS OF BENZOIN

The Benzoin Condensation is a coupling reaction between two aldehydes that allows the preparation of α-hydroxyketones. This method is only suitable for the conversion of aromatic aldehydes.

The reaction is catalyzed by KCN which produces cyanide (CN −) ions in solution.

Please note that the benzaldehyde used should be freshly distilled (to remove any benzoic acid).

H

O

KCN/H2O

EtOH, reflux

O OH

Benzoin

2

*

mp. 134-135 C

MECHANISM

Cyanide (CN-)

• Good nucleophile. Stabilizes the resulting carbanion. Serves as a good leaving group.

O

H

O

HCN

CN

H2O

OH

HCN

OH

OH

CN

OH

CNPh

O

H

OH

OCN

Protontransfer

O

OHCN

O

OHCN

O

OH

Step 1. SET UP

• Dissolve 1 g KCN in 20 ml of distilled water in 250 ml rbf.

• Add 40 ml 95% EtOH, 20 ml fresh benzaldehyde, and one boiling chip.

• Reflux gently in heating mantle for 45 min.

• Cool the mixture, then crystallization occurs. Collect the crystal by filtration and wash with 1:1 cold EtOH/H2O, dry your crystals.

• Check the color of your benzoin, weigh, calculate the yield, then Determine the mp.

water in

water out

Cyanide is VERY TOXIC and may be fatal, even at low concentrations.

Cyanide ions, in the present of acid, produces HCN gas , which is lethal at 300ppm, so NO ACID should ever be poured in that sink even in the hood.

This experiment should be done in the fume hood. Dispose of cyanide waste as directed by your lab

instructor.

CAUTION

Step 2. REDUCTION OF BENZOIN

O OH

NaBH4

HO OH HO OH

+

+/- mixture meso isomer

Mp 122-123 oC Mp 137-139 oC

Sodium borohydride (NaBH4) is commonly used as a

source of hydride (H−).

Hydrobenzoin is formed as different isomers.

FELKIN-ANH/CRAM’S RULE

When there is a chiral center at the carbon next to the carbonyl (the α carbon), there is a preference for which side the nucleophile will attack.

According to the Felkin-Ahn model, the more favorable conformation for the molecule is either A or B.

Conformation A will be favored over conformation B because there will be less steric repulsion between GS and R1.

Step 2. SET UP

• Dissolve 1 g benzoin in 10 ml of EtOH in 50 ml Erlenmeyer flask.

• Add 0.2 g NaBH4 in small portions with swirling.

• The reaction mixture was swirled at rt. for 20 min.

• Cool the flask in ice bath, add 15 ml water, then 0.5 ml 6 M HCl. Add 5 ml more water and continue swirling the flask for 20 more min.

• Collect the product by filtration and wash with H2O.

• Crystallize the solid using EtOH/water, dry the crystals overnight. Check the color and weight.

• Determine the mp.(to determine which isomer formed) And IR spectrum of dried crystals.

CAUTION

NaBH4 is very reactive with water. Do not use near the

sink or where water is close by.

Be careful when stopping the reaction with HCl and

water. Add slowly to the cooled reaction mixture.

Step 3: OXIDATION OF BENZOIN

O OH

Benzoin

O O

Benzil

*H

O OH2

NO O

O

O O N

O

OH + HNO2

decompose

NO2 gas evolvedmp. 94-95 C

Step 3. SET UP

• Place 10 g of benzoin in 100 ml flask, add 34 ml conc. HNO3.

• Heat the flask gently on steam bath for 30-40 min. with swirling.

• Cool the mixture in ice bath, pour the contents into 250 ml of water containing some ice. Break up the lumps of yellow benzil. Collect the product by filtration and wash with ice cold EtOH.

• Recrystallize the product with minimum MeOH, dry your crystals. Check the color and weight.

• Determine the mp.

CAUTION

Concentrated HNO3 is very corrosive and is an

oxidizer. Be VERY careful when handling this reagent

in the lab.

NO2 gas is evolved in this reaction, please DO NOT

inhale these fumes.

Step 4: ALDOL CONDENSATION.Synthesis of tetraphenylcyclopentadienone

Carboxylic AcidsR O H

O

pKa

5

Amide R NH

H

O

Aldehyde H CH2

H

O

KetoneR C

H2

H

O

15

17

20

Ester RO CH2

H

O

25

O O

O

Ph

PhPh

Ph

O

+ OH

Dibenzyl Ketone

Benzil

mp. 220-221

Step 4: ALDOL CONDENSATIONContinued

Formation of an enolate anion. Addition of that enolate to the carbonyl group of another molecule. Proton transfer, usually from solvent. Only carbonyl compounds that possess alpha protons can undergo Aldol

condensation.

H3C

O

CH2

OEt

H3C

O

CH2

(+HOEt)

H3C

OH3C

Example:

H3C

O CH3

CH3

OH OEt

H3C

O CH3

CH3

OH

H

ALDOL CONDENSATION: Dehydration

• Condensation is pushed forward via dehydration.• This involves deprotonation of another alpha proton followed by

loss of hydroxide.• The formation of the ,-unsaturated system compensates for the

hydroxides poor leaving ability.• Acid or based catalyzed dehydration is promoted at higher

temperatures.

H3C

O CH3

CH3

OH

HH3C

O CH3

CH3

EtO

MECHANISM: Enolate Formation

Ph

O

PhOH

H HPh

O

Ph+ H2O

Ph

O

PhOO

Ph Ph

+

OO

PhPh

PhPh

O

OO

PhPh

PhPh

O

OHO

Ph Ph

PhPh

O

HOH

O

PhPh

PhPh

O

H2O

MECHANISM CONTINUED

O

PhPh

PhPh

O

H H

O

Ph

Ph Ph

Ph

OH

O

PhPh

PhPh

O O

OPh Ph

PhPh

O

OPh Ph

PhPh

H2O

O

OHPh Ph

PhPh

H OH

Step 4. SET UP

• Place 0.01 mol of benzil, 0.01 mol dibenzyl ketone and 10 ml triethylene glycol in 50 ml flask, heat the mixture to be dissolved on hot plate then remove from heat.

• Make the base (1 ml of 40% benzyl trimethyl ammonium hydroxide in MeOH in a test tube).

• Place a thermometer into the flask, when it reach 100 °C, then add the base. Swirl once to mix then remove from heat. Crystallization will start in 10-15 min.

• When the temperature drops to 80 °C, cool the flask under tap water, then add 10 ml MeOH. Stir or swirl to a slurry, collect the product and wash with cold MeOH until the filtrate is dark purple-pink, dry your crystals.

• Check the weight of product, Determine the mp. (if the product is impure it can be crystallized from triethylene glycol at 220 °C)

Step 5: DIEL’S-ALDER reaction

This reaction involves the addition of an alkene to a conjugated diene. It is a concerted reaction that forms a cyclic product, via a cyclic

transition state. Hence it is called “cycloaddition”. The reaction is found to be promoted by having electron donating

groups on the diene (i.e. electron rich) and electron withdrawing groups on the alkene (i.e. electron deficient).

OCN

MeO2C

CO2Me

CO2Me

CO2MeCO2Me

CO2Me

O

O

Electron rich dienes

Electron DeficientDienophiles

STEP 5: Synthesis OF Dimethyltetraphenylphthalate

NOTE: (a)The dienophile used is a powerful lachrymator, it should be always handled in the fume hood.(b) Reaction proceeds with the evolution of CO(g) which is toxic.

dimethyl tetraphenyl phthalate mp. 258 C

Step 5: MECHANISM

CAUTION CO(g) is toxic

Step 5. SET UP

• Add 0.005 mol of tetraphenylcyclopentadienone (step 4 product) and 0.0075 mol dimethylacetylenedicarboxylate in 10 ml of o-dichlorobenzene in 100 ml rbf with a boiling chip. Attach a condenser (no water flowing).

• Heat gently in hood to boil (CO evolution) about 10-15 min until no more color change. Control the vapor not to rise into the condenser. (if your starting material is pure, the pure adduct is white, so watch the color changes from purple to pale tan.)

• Cool to 100 °C (thermometer) and add 15 ml MeOH, then stir slowly to let crystallization proceed. Cool and collect the product by filtration, then wash with cold MeOH.

• Determine the mp. Weight of the product, color.

NMR Spectroscopy

1H, 13C, 15N, 19F and 31P all have nuclear spin that can be exploited by organic chemist to deduce a compounds structure.

Different types of protons/carbons are represented by a specific chemical shift in a NMR spectra.

NMR: continued

There are three major factors that influence chemical shift ():

The deshielding effect: Is the result of electronegative groups reducing the electron density around 1H and 13C nuclei which allows these nuclei to be exposed to a higher magnetic field, resulting in an increase in their chemical shift ().

NMR: continued

Anisotropic effect: Due to magnetic fields generated by π-systems. Depending on the position of a proton in this field, it can be

either shielded (smaller ) or desheilded (larger ).

NMR: continued

Hydrogen Bonding Protons involved in H-bonding( e.g. OH, NH) are

deshielded and observed over a large range of chemical shifts.

Leaves the assignment of OH or NH to the end. Or use D2O to identify those peaks.

NMR: continued

Interpreting 1H-NMR How many types of Hs are present? Indicated by the

number of chemical shifts in the spectra. What types of Hs are present? Indicated by the position of

the chemical shifts in the spectra. How many of each type of H are present? Indicated by the

area under each chemical shift, which is proportional to the number of protons.

What is the connectivity of the Hs? Indicated by the splitting pattern of the chemical shift.

NMR: continued

13C-NMR

• 13C has only 1.1% natural abundance versus 100% 1H, therefore is about 400 times less sensitive than 1H nucleus to NMR.

• Due to this low abundance, 13C-13C coupling is not seen.

• The peaks in 13C spectra are shown as single lines and the number of peaks indicate the number of types of carbons present.

• Chemical shifts for 13C-NMR spectra usually occur between 0-220 ppm.

13C-NMR

13C-NMR: continued

Interpreting 13C-NMR How many types of Cs are present? Indicated by the number of

chemical shifts in the spectra.

What types of Cs are present? Indicated by the position of the chemical shifts in the spectra.

Benzaldehyde H NMR

H

O

Benzaldehyde C NMR

H

O