CH 203 Laboratory-Fall 2013

Experiment 1:Isolation of the Active Ingredient in an Analgesic Drug

Instructor: Dr. Rebecca Loy

Laboratory Coordinator: Dr. Rebecca Loy Office Hours: SCI 358 Tuesday 11 am-12pm, Thursday 3-4 pm

Required Text: D.L. Pavia, G.M. Lampman, G.S.Kriz,Jr.and R.G. Engel, Introduction to Organic Laboratory Techniques, A Microscale Approach, edition 5th Edition – BU custom edition, W.B. Saunders, 2013

Last year’s 4th edition will work

Required Equipment:

• Safety glasses• Lab coat• Lab notebook (with carbon copies)

Lab Schedule

• You will have lab every other week. Prelabs lectures every week.

• All labs meet in SCI 348. You will be assigned a lab room (A, B or C)

• You will be assigned either an A or B week. A week starts lab the week of September 9. B week starts the week of September 16. Some lab days will not have both A and B weeks available. See the syllabus for details. If you have a preference for A or B week and both are offered fill out the form at the below website:

http://www.surveymonkey.com/s/CRQPJS9

• All lab sections have now been closed. If you do not have a lab section or need to change a lab section please fill out a change of lab form on the website below:

http://www.surveymonkey.com/s/CSDC7RF

• Lab assignments will be posted on blackboard on Saturday, September 7 b7 11 pm.

Grading: The laboratory grade comprises 15% of the overall course grade. There will be 6 labs. Each lab scored out of 100 points. 3 sections: Prelab, Experimental Skill and observations and postlab worksheet or write-up. Tentatively a lab exam is planned for the last prelab lecture of the semester 12/4, 12/5 and 12/6.

I) Prelab 1) Objective: What are the goals of the experiment 2) Main reaction 3) Mechanism (labs 5 and 6) 4) Experimental Procedure (in your own words, one side of the page) 5) prelab questions (if assigned) (Make sure to do the reading assignment posted on the syllabus)

II) Experimental Skills/Observation 1) Obtaining product 2) adherence to safety rules 3) cleanliness 4) organizational skills 5) record of observations in lab notebook

III) Postlab worksheet or Lab write-up (includes calculations, results and discussions)

Grading

All experiments and lab reports are done individually.

Example Prelab

THE MANNICH REACTIONObjectiveTo synthesize 3-dimethylamino-1-phenyl-1-propanone by the Mannich reaction and to record the product’s NMR spectrum.Main reaction

+CH3

O

H H

O

O

H H

N

H HCH3

CH3N

H

CH3CH3

+ + H2OH

For the first lab just draw the analgesic structures for this part

Reaction mechanism (not needed for the first 3 labs)

Place

 

15 g acetophenone

13 g dimethylamine hydrochloride

5 g paraformaldehyde

1 mL conc. HCl

20 mL 95% ethanol

 

in 250-mL Erlenmeyer

 

Density of acetophenone = 1.03 g/mL, so 15

g = 14.6 mL

(This part is filled out during lab)

Dimethylamine hydrochloride and

paraformaldehyde are colorless crystalline

solids.

 

Acetophenone is oily colorless liquid having a

strong odor of perfume; measured it out by

volume.

Heat flask on steam bath 2 hr.

 

 

Begin heat 1:24 P.M.

End heat 3:05 P.M.

Mixture started clear.

Began to turn yellow at about 2:00 P.M.

Very dark yellow after about 2:30 P.M.

No more perfume smell! It’s GROSS!!!

Procedure and Observations

Lab Reports and Worksheets

- Lab information sheets for each experiment will be posted on blackboard under experiments. If you have the new 6th edition of the lab manual they are in the back of the manual. Lab information sheets will replace instructions found in the lab manual. Follow these directions!!

- Prelabs will be due immediately after lab. Turn in white sheet and keep carbon copy for yourself.

- Lab reports or worksheets for the lab will be due one week later by 5 pm in the wooden mailboxes across from the chemistry office in SCI 299, next to SCI 296, make sure to include your TF’s name and section on your report.

- A sample prelab and observations is posted on blackboard.

- For experiment 1, a worksheet needs to be turned in 1 week after lab. The worksheet is posted on blackboard under experiments->experiment 1.

Regrades and Make-up Labs

DIFFERENCES OF OPINION IN GRADING: If you believe that an error was made in correcting a laboratory write-up, bring the matter to your TFs first. If unresolved, bring it to Dr. Loy within one week of your receiving it and the problem will be considered by the staff. Write out the grading error on a separate piece of paper, attach it to your lab report and turn it into Dr. Loy. All of your lab report will be regraded so your score could go down.

Make-up Labs: Students are expected to perform all experiments. To account for absences which may result from illness, religious holidays, death in the family, etc., the following schedule of make-up labs will be offered: Lab 1&2 Monday, October 7 5:30-9:00 PM Labs 3&4 Monday, November 4 5:30-9:00 PM Labs 5&6 Monday, December 9 5:30-9:00 PM

ONLY ONE MAKE-UP LAB IS ALLOWEDPlease fill out the form at the below website:http://www.surveymonkey.com/s/QQFYTY2

Laboratory Safety

• Safety glasses/goggles• Lab Coat• No skin showing neck down (ie no shorts or open toed shoes)• Long hair tied back• Gloves

You will lose points for lab if you do not follow the above rules or be asked to leave lab.

Hoods

- All chemistry must be done in your hood. No liquids should be opened unless they are in a hood.

- Do not put your head in the hood.- Keep the hood sash as low as

possible. Keeps you safer.- Two people to a hood.

Lab Kits

- You will be given a microscale lab kit. You must turn in your BU ID to get the kit, so remember to bring it to lab. If you don’t have a BU ID, a driver’s license will suffice.

- You must return the kit clean. (Soap and water then acetone)

- You must clean-up remaining glassware and hood/bench.

- Always clean your glassware with soap and water. Lots of things will stick to glassware that can only be removed with soap and water. Acetone is expensive. Do not waste it.

Waste Disposal- Organic chemicals do not go down the sinks (this includes acetone). Dispose in

proper waste container)

Broken glassware, disposable glassware (pipettes) Needles, sharps

Securing your Belongings

• You must put your belongings in the lockers provided when you enter the lab. All you should have out is your safety equipment (glasses, lab coat), your lab notebook, pen and calculator.

• The lockers are not secure. There have been thefts. Do not leave any valuables in them. Please bring a lock to secure your locker.

• BU is not responsible for any lost or stolen items.

Isolation of the Active Ingredient in an Analgesic (Pain killer)

Active ingredients

C

CC

C

CC C

O

O

O

COH

H

H

H

H

HC

CC C

CC

N

H

HH

O

HC

OC

HH

H

HH

CC

C CC

CC

H

HH

C

H

OH

CH

HH

O H

CC

C

H

H

HHH

H

HH H

OH

O

O

O

Acetylsalicyclic Acid(Aspirin)

NH

O

HO

OOH

Acetaminophen Ibuprofen

Experiment 10 in lab manual, 5th ed: pg 9 (plus handout on blackboard)

Aspirin

OH

O

O

O

Acetylsalicyclic Acid(Aspirin)

-Used in the treatment of fever, pain and inflammatory disease

-Naturally found in spiraea and willow bark. It has been used for thousands of years for treatment of pain and fever by using the natural source.

- First synthesized in 1859, Bayer starting selling in 1899.

Acetaminophen

NH

O

HO

Acetaminophen

naphthalene

- Two doctors were treating patients for worms and thought they had give them napthalene, but accidentally gave them acetanilide instead, which was found to reduce fever.

- A chemist at Bayer needed to get rid of p-aminophenol and converted it to phenacetin, which was sold until about 1953 instead of acetaminophen because it was supposed to be toxic.

NH

O

acetanilide

OH

NH2

p-aminophenol

O

NH2

O

NH

O

phenacetin

- 1953, Acetaminophen found to be non-toxic and began to be sold.

Ibuprofen

OOH

Ibuprofen

- Aspirin and acetaminophen have negative side effects so other analgesics were developed.

- First discovered by the Boot’s group in England in the 1960s.

- Once of the scientists who discovered it initially tested it on himself to treat a hangover.

- Initially used in 1967 to treat rheumatoid arthritis.

- Found to be more potent then acetaminophen and aspirin

Purification Scheme: Remove binder

+ Analgesic =

Crush with pestle

Goal: Extract active compound in an analgesic from a pill and isolate it, and determine the quantity of the active ingredient.Make sure to note the amount of analgesic that is in each pill

C OH

H

HH

methanol

Transfer pipette Pasteur pipette

Extract

Conical vial

Safety Hazards methanol: toxic and flammable

Falcon tube

centrifuge

Centrifuge

After centrifuging

Binder is insoluble in methanol

Pipette Column

Safety hazard: alumina: irritating dust

Solvent Removal and Isolation

Blow off methanol with air while heating

Filter product

Melting Point

- Add solid to melting point capillary tube by inverting and gently tapping.

Melting Point

Ramp melting point apparatus slowly and watch to see what temperature melts. Record a range. Record what temperature it starts to become a liquid and what temperature it is completely liquid. If you want to know approximately where to start you can look up the known melting point of your compound.

Melting point tells you about the purity of the compound. If the melting point is drastically off from the known value it is probably impure