A COMPILATION OF SYNTHESES OF SELECTED ORGANIC COMPOUNDS AND NATURAL PRODUCTS(A Laboratory Manual for Pharmaceutical Chemistry 2)

Henedina A. Maini, RPh

May 2014

FOREWORD

The experiments included in this manual have been selected from various sources and were chosen in order to aid students in their understanding of how a pharmaceutically important compound is produced synthetically from organic and inorganic chemicals commonly seen in the College of Pharmacy laboratory. The process of preparation also includes testing for the identity of the products produced using official identity tests coming from available editions of the United States Pharmacopoeia and the National Formulary and determination of physico-chemical constants, such as melting point, boiling point and solubility characteristics, to name a few.It is also a means by which students studying Pharmacy would be introduced to the rudiments of laboratory work, giving them ample exposure in the implementation of procedures as presented to them in the different experiments, as well as making them improve on their skills acquired through years of studies, instilling in them the value of time, honesty, patience and hard work.The experiments have been validated in order to minimize unexpected reactions that might arise from the conduct of the same.It is our hope that this simple contribution would instill in the students the importance of understanding the basics of Organic Chemistry in relation to the biologically-active compounds identified.

H. A. Maini, RPh

PROPER CONDUCT OF STUDENTS IN THE LABORATORYIt is expected of every student enrolled in Pharmaceutical Chemistry 2 to observe the following:1. WEARING OF PROPER PPE (PERSONAL PROTECTIVE EQUIPMENT)The safe way is the right way to do your experiment. It is without saying that students have to be protected from the hazards of conducting an experiment might bring, thus, a student is expected to have the following minimum requirements when they enter the laboratory:1. Laboratory gown2. Laboratory shoes3. Head cap4. Safety goggles5. Face mask6. GlovesSafety goggles should be worn at all times inside the laboratory. Personal effects: wear proper clothing (including protective clothing when handling corrosive, toxic, or flammable materials). Avoid loose sleeves, loose cuffs, and bracelets. Be careful with long hair. Proper shoes are required (no sandals).

On top of this, students in a group should have in their lockers the following:7. Test tube holder8. Test tube brush9. Soap solution or detergent10. Bottle brush11. Oil cloth12. Rags13. Plastic bags14. Pot holders15. Various sizes of corks16. Scissors

Be able to use all safety devices and protective equipment provided for your use and know their location (eyewash fountain, shower, fire extinguisher).This minimum requirement would ensure to some extent that a student would be partly ready in conducting the experiment that is assigned for the day. Of course, other requirements for the experiment should be requested from the Instrument Room.

2. DO NOT EAT OR DRINK IN THE LABORATORY (and do not store food in the refrigerators). Smoking in the laboratory is absolutely forbidden.

3. HORSEPLAY in any form is dangerous and prohibited. Do not run in laboratory areas.

4. REPORT TO YOUR LABORATORY INSTRUCTOR ALL UNSAFE CONDITIONS, unsafe acts, and "near misses" that might cause future accidents. Report any accident or fire, no matter how trivial, to the laboratory Instructor.

5. HAZARDOUS CHEMICALS: a. Be especially mindful of fire hazards when you or your lab neighbors are working with flammable liquids. b. Hazardous Substances: Know common explosive, toxic, and carcinogenic materials and use them only with adequate safeguards.

6. NEVER LEAVE A REACTION OR EXPERIMENT RUNNING UNATTENDED, unless you have told your lab partners enough about it to deal with potential hazards while you are away.

7. KEEP HOOD AND BENCH TOPS AREAS CLEAN AND WORKABLE SPACE MAXIMIZED.8. ADVANCED READING OF THE EXPERIMENTStudents are expected to have a preliminary reading of the exercises in order for them to be aware of the conditions and requirements of the experiment/s scheduled for the day. Plan your work. Follow instructions. If after reading the instruction and procedure you still do not know how to do the experiment safely, ask your laboratory instructor. Always be ready for a quiz on the scheduled experiment.

9. PREPARATION OF THE PRE-LAB REPORTPreliminary data should be obtained for the compound to be synthesized.

10. REQUISITION OF CHEMICALS AND GLASSWARERequisitions for the said experiment scheduled to be performed should be requested from the Instrument Room THREE (3) DAYS BEFORE THE SCHEDULED EXPERIMENT by filling up the necessary forms pertaining to the needs of the experiment. Requisitions should be SIGNED BY THE LABORATORY INSTRUCTOR as well as the STUDENT REPRESENTATIVE OF THE GROUP MONITOR identified or assigned for the said experiment.

Test solutions and chemicals needed for the experiment should also be prepared (if there is a need to).

11. FOCUS AND PRESENCE OF MIND IN THE CONDUCT OF THE EXPERIMENT/S.There is no substitute for COMMON SENSE.Simple rules learned through the study of chemistry, e.g. Acid to water NOT water to acid, in the previous year levels would certainly help the student in hurdling the chemical reactions that he/she will meet in this course. Thus, focus and presence of mind during the conduct of the experiment/s is A MUST.

LABORATORY HAZARDS OVERVIEW

Chemical HazardsEvery chemical is a poison, depending on the dose taken. We handle hazardous chemicals in our everyday lives, from the gasoline we use to run cars to using chlorine bleach to clean the laundry. The keys to safe use of these and any chemical are: understanding the hazards of each chemical; knowing and using safety measures to minimize these hazards. However, it is easy to forget all these and treat hazardous materials casually. Precautionary measures have to be taken seriously. Simple precautions can be a lifesaver; use them as you use a harness when driving a car.

Liquid Chemical HazardsLiquid chemicals present the greatest potential risk for injury: 1. they have to be handled (transported, poured, and mixed) to be used; 2. theres a wide variety, each with a different set of hazards and precautionarymeasure required for use.

Chemicals in the laboratory can cause severe burns, tissue,and organ damage, and can ignite and explode. The greatest health risks posed by liquid chemicals are physical (fire, explosion), direct contact with skin and eyes (tissue damage), and inhalation (pulmonary damage or long term chronic effects). For detailed hazard information, consult the pertinent MSDS.Make every effort to understand the chemical processes you use and respect the chemicals you work with. Knowing the general rules on how to safely transport, pour, use, and dispose of these chemicals is every laboratory user's responsibility.

Gas HazardsCompressed gases pose both chemical and physical hazards. Some of the gases used are inert; others are toxic, corrosive, flammable, or explosive. The primary health risks posed by gases are the physical hazards (fire, explosion) and inhalation (toxins and corrosives). Because of these potential hazards, as a laboratory user, one must be always aware of the types gases and the hazards posed in the equipment being used.

Electrical HazardsElectrical shock hazards are present wherever electricity is used. Although equipment is interlocked to prevent operator exposure, one must be aware the electrical hazards for the tool you are using. Burns occur wherever the body completes a circuit connecting the power source with ground. Although the resistance of dry, unbroken skin to electric current is relatively high, the amount of current needed to kill a person is small. It is easy to exceed lethal levels of current, especially if the skin is broken, wet, or damp with sweat.Unless it is in your training, never open electrical enclosures or cabinets on equipment, even when the power is off. If you feel an electrical "tingle" when you touch a piece of equipment, stop using the tool and immediately notify a maintenance staff person. Never stick your hands, fingers or conductive tools inside equipment. Immediately notify the maintenance staff of any potential electrical hazard that one notice.Electronic devices that are not allowed to be used in the laboratory are personallistening devices (iPods and such) as these may prevent the user from hearing alarms or lab announcements.Other HazardsUltraviolet Radiation UV exposure is a potential risk. High power UV lamps as they are mercury-based, they pose a chemical risk. If a UV lamp should break or explode, do not attempt to clean up; instead, isolate the immediate area and call staff.Electromagnetic Radiation may be generated by equipment. Report any damage to shielding on the equipment or cables.

Liquid ChemicalsLiquid Chemical Hazard ClassesCorrosive: A corrosive (or "caustic") chemical destroys or permanently damages living tissue. On contact, corrosives can destroy skin and underlying tissues. Splashes in the eyes can cause blindness. Inhalation of vapors can destroy lung tissue.Corrosives in the laboratory include acids and bases. In case of localized external exposure, promptly flush the affected area with plenty of water, for at least 15 minutes. Remove clothing while under the shower and flush for at least 15 minutes. Exposure of corrosives to the eyes is extremely serious; flush immediately, either with a spray gun at your wet bench or the nearest eyewash station. Eyes should be rolled up and down, and side to side, continuously, to allow clean water to flush behind the eyeball. For any exposure to corrosives, one should get help. The victim should be taken to the emergency center for evaluation and treatment.

Oxidizing agentAn oxidizing agent is a chemical compound that has a pair of electrons to donate to an electron-accepting, reducing agent. Often, they contain reactive oxygen. When mixed with compounds that can act as reducing agents, the result is often a violent reaction, possibly an explosion. Oxidizing agents should not be stored or mixed with solvents, which generally makeexcellent reducing agents. Oxidizing agents are stored in the chemicals pass-through. One oxidizing agent is hydrogen peroxide (H2O2). Nitric acid (HNO3) is an oxidizing agent as well as a corrosive. In the laboratory, the main principle behind segregation of chemicals is to keep oxidizing agents away from flammable chemicals (namely, solvents) and any combustible materials (some chemicals, materials like laboratory wipes).

Water reactiveWater reactive describes compounds which very quickly generate heat and/or gas upon mixing with water. These are often concentrated acids or bases. The primary hazard presented by water-reactive compounds is incomplete mixing, which can lead to superheating and explosion. Thus, water-reactive mixtures should never be poured directly into a sink drain. Aspirating water reactive mixtures at the wet benches is standard practice; the high dilution factor and rapid mixing dissipates heat and prevents superheating.

FlammablesFlammables include most solvents, such as acetone, isopropanol, and methanol. The flash point of a flammable is the concentration in air above which the vapors from a flammable can ignite and explode. The source of ignition may be heat (such as a hot plate) or a spark (such as from an electrical tool). Because the vapors can travel over considerable distances, the source of ignition can be far away from the flammables container itself.To minimize hazards, always work well within the exhausted area of the appropriate bench (behind the red line). The air pulled into the exhaust area will keep the concentration of vapors below the flash point. Where possible, minimize the quantities of flammables used. Before working with flammables, always note the location of the nearest safety shower andfire extinguisher. Flammables should be stored in the designated flammables cabinet; no flammables may be stored in the laboratory. Flammables must be kept away from oxidizing agents.

Toxin/Poison A toxic material is one that has poisonous or harmful effects. There are formal, quantifiable definitions as to what comprises a toxic material and to what degree it is toxic. These definitions are based on lethal dosages for laboratory animals when administered orally or through inhalation.

Non-toxicA non-toxic material is one that is not likely to result in harmful effects with normal use. This designation is used sparingly. Pure water is considered non-toxic.

Specific Hazardous Liquid ChemicalsSolventsFlammable SolventsAcetone, isopropanol, and methanol may be found in the solvent wet benches. These chemicals are all flammable solvents with low flash points. This means that at sufficiently high vapor concentrations, they can be easily ignited at room temperature and, therefore, pose significant fire hazard. Thus, solvents should not be used on or near hot plates or near any electrical system. Solvents may also ignite or explode when brought into contact with chemical oxidizing agents (such as many acids) and so should not be mixed with, nor collected in the same waste container as these compounds. Standard solvent waste should be disposed of in the solvent carboy or collected locally.These and other solvents must be stored in the designated flammables cabinet in the service area and may be transported in the laboratory only if carried in metal carts. Solvents may be used only in designated solvent hoods.

Chlorinated SolventsChlorinated solvents (such as chlorobenzene, trichloroethylene [TCE], and methylene chloride) may be present in some processes, although these have been phased-out of general use. Long term, repeated exposure to some chlorinated solvents is correlated to cancer and liver and nerve damage. Because of environmental hazards, chlorinated solvent waste must be collected in a waste container, separate from other kinds of liquid solvent waste.

Oxidizing AgentsPeroxidesAll peroxides are highly oxidizing materials; energy is released when they are reacted. Some peroxides are unstable, and can explode. Extreme care should be used in mixing solutions containing peroxides. Peroxides are incompatible with all forms of organic solvents and flammable materials.

Nitric AcidNitric acid is also water reactive (heating upon addition of water). All oxidizers should be kept away from solvents, bases, and flammable materials.

Alkali/BasesAlkaline compounds, or bases, are the chemical opposite of acids, and may react violently when mixed with them. They are most commonly used in the laboratory in lithography and etch. Alkalis are caustic, so protective gear should always be worn when working with them to prevent contact with skin and eyes.

Specific Hazardous GasesCorrosive GasesHydrochloric acid (HCl)HCI gas is extremely corrosive to almost everything, including stainless steel. It is used for cleaning/etching deposition chambers.

Ammonia (NH3)NH3 gas is a severely corrosive alkaline vapor with a pungent odor. It is shipped in the cylinder as a liquid under its own vapor pressure of approximately 9 atm. NH3 gas is used in oxynitride and nitride film deposition (plasma and CVD.)

WHAT TO DO IN AN EMERGENCY

TYPE OF EMERGENCY RESPONSEFire Alarm Sounds Leave the building immediately. Meet at the Evacuation Assembly Point DO NOT re-enter the building until cleared.

Health ThreateningFire, toxic spills, gas leak Pull the fire alarm, if alarm is not already sounding. Leave the building immediately. Meet at the Evacuation Assembly Point DO NOT re-enter the building until cleared.

Major Earthquake Take cover; wait for shaking to stop. Leave building & meet at Evacuation Assembly Point DO NOT pull the fire alarm unless there is a health-threatening hazard.

Life-Threatening Medical Emergency(if in doubt, treat as an emergency) Call out for help. Dial the emergency number immediately (DO NOT hang up until told to do so.) DO NOT move victim unless necessary. First aid kit/AED/Oxygen Units located near the instrument Room

Non-Health Threatening Emergency (Building and facilities) During work hours: call Kaycie Baliza at the Deans Office; in the laboratory, call Ryan Quiming. After hours, call ST Gate information desk.

Electrical Power Outage Emergency backup lights should come on within 15 seconds. (normal buildingoperations will be interrupted until regular power is restored)

Chemical Spill Isolate the affected area. Leave immediate area and make sure others leave also Work hours: page Kaycie Baliza of the Deans Office or Ryan Quiming of the Instrument Room Off hours: Call ST Gate Information Desk

Odor in the Lab Leave immediate area and make sure others leave Work hours: page staff and call Ryan Quiming of the Instrument Room

FORMAT OF LABORATORY REPORT

The laboratory report will be a group report. Laboratory reports, composed of the pre-lab and post lab reports, should be written in short bond paper to facilitate the submission of the compiled report at the end of the semester. Writing of laboratory report should follow the following format:

1. PRE-LAB REPORT (30 pts)

EXPERIMENT NO.TITLE OF THE EXPERIMENT

GROUP NO.START OF EXPERIMENT (DATE)NAMES OF GROUP MEMBERSEND OF EXPERIMENT (DATE)

I.OBJECTIVES: (Minimum of 2, maximum of 5)II.DIAGRAM OF THE PROCEDUREIII.PRELIMINARY DATA ON THE COMPOUND TO BE PREPAREDA. PHYSICAL APPEARANCEB. PHYSICO-CHEMICAL PROPERTIES, EX. MELTING POINT (IF SOLID), BOILING POINT (IF LIQUID)IV.CHEMICAL REACTION INVOLVED IN THE SYNTHESIS V.COMPUTATION FOR THE THEORETICAL YIELDVI.TEST FOR IDENTITY OF THE COMPOUND TO BE PREPARED (MINIMUM OF TWO TESTS, WITH THEIR CORRESPONDING CHEMICAL REACTIONS)

2. POST-LAB REPORT (70 PTS.)

VII.DATA/RESULTS OBTAINED FROM THE CONDUCT OF THE EXPERIMENT (Should be written on the data sheet for each of the experiment)VIII.DISCUSSION OF RESULTS (This should contain the problem/s encountered in the conduct of the experiment and what remedy/ies have been applied to solve this/these problem/s)IX.ANSWERS TO QUESTIONSX.REFERENCE/S USED

NOTE: It is expected that the preparation of laboratory report SHOULD ROTATE among the members of the group. An ASTERIX should mark the name of the student/s who prepared the report.

LABORATORY GRADING SYSTEMIndividual as well as group grades will be generated from the:Laboratory performance30%Individual10%Group20%Products submitted 5%Examinations40% Periodical exams20%Quizzes20%Reports submitted10%Research on a synthesis10%Compilation of reports 5%

T o t a l 100%

TABLE OF CONTENTS

TITLE PAGEFOREWORDPROPER CONDUCT OF STUDENTS IN THE LABORATORY. . . . . . . . . . . . . . . . . . . . 3LABORATORY HAZARDS OVERVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5WHAT TO DO IN CASE OF AN EMERGENCY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10FORMAT OF LABORATORY REPORT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12LABORATORY GRADING SYSTEM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Experiment 1. EVALUATION AND TESTING OF ORGANIC COMPOUNDS . . . . . . . 15

Experiment 2: SYNTHESIS OF BENZOIC ACID . . . . . . . . . . . . . . . . . . . . . . . . . . . .21Experiment 3: SYNTHESIS OF SULFANILAMIDE . . . . . . . . . . . . . . . . . . . . . . . . . . 25Experiment 4: SYNTHESIS OF ASPIRINExperiment 5: SYNTHESIS OF METHYL SALICYLATEExperiment 6: DIAZOTIZATION AND SYNTHESIS OF AZO DYE, ORANGE II DIHYDRATE. Experiment 7: SYNTHESIS OF METHYL ORANGEExperiment 8: SYNTHESIS OF AMYL ACETATEExperiment 9. SYNTHESIS OF AZELAIC ACID FROM CASTOR OILExperiment 10. RESEARCH ON SYNTHESIS OF ORGANIC COMPOUNDS FROM NATURAL PRODUCTS

Experiment 1.EVALUATION AND TESTING OF ORGANIC COMPOUNDSI. IntroductionOrganic compounds can be simply described as compounds consisting mainly of the elements, carbon and hydrogen. However, there are some other elements that can be incorporated into a chemical structure of an organic compound such as oxygen and nitrogen, thus, producing a vast array of organic materials that are varying in their physico-chemical properties and characteristics. These physic-chemical characteristics can be used as a means to identify them, if not, to characterize them apart from the other existing chemical compounds.Classification of organic compounds vary, depending on how they are chemically structured. Examples of which are organic acids, having the general formula of RCOOH; alcohols, ROH; esters, RCOOR; and ethers, ROR. Depending on their chemical classification, the presence of these organic compounds can be ascertained by evaluating their physical attributes and by using standard chemical tests to identify their presence.II. ObjectivesThe objectives of this experiment are to:1. familiarize the students with the different types of organic compounds;2. differentiate organic compounds in terms of their intrinsic properties;3. differentiate organic compounds in terms of their behavior towards ignition;4. characterize them using chemical tests; and5. enable students to gain skills in evaluating organic materials.

III. Materials and equipment

Test tubesTest tube rackTest tube holderSpot plateEvaporating dishCalibrated dropperBurnerMortar and pestleLitmus papers (blue and red)pH paperPersonal protective equipment (PPE)

Solvents to use:Water5% Sodium hydroxide5% Sodium bicarbonate5% Hydrochloric acid

Chemicals to evaluate:1. Ethanol2. Phenol3. Ethyl acetate4. Acetone5. Formaldehyde6. Toluene 7. Diethylether8. Methanol9. Salicylic acid10. Benzoic acid

Equipment:Melting point apparatus

IV. Special instructionsStudents are expected to take precautionary measures in handling the organic compounds to be tested and reagents to be used in this experiment.Students are NOT ALLOWED TO TASTE sample materials unless directed.Students are requested to observe EXTREME CAUTION when handling chemicals.

V. ProcedureA. Evaluation of the physical state of the sample.1. Observe the physical state of the sample at room temperature.2. Note the color of the sample.3. Describe the odor of the sample.

B. Solubility property determination.FOR LIQUID SAMPLES.1. Calibrate a dropper to 3 ml volume.2. Take 10 drops of each of the liquid samples to be tested and place them separately in clean and dry test tubes numbered as the number of the samples to be tested.3. Drop by drop, add water by using the dry calibrated dropper.4. Note any change in color, warming effect, effervescence. Describe the solubility of the sample in the solvent used, depending on the number of drops of the solvent used to solubilize the sample being evaluated.5. Describe whether the sample was miscible, slightly miscible and immiscible.6. If insoluble, repeat steps 2-5, this time using 5% NaOH as solvent.7. If soluble in 5% NaOH, repeat steps 2-5, this time using 5% NaHCO3 as solvent.8. If insoluble in 5% NaOH, repeat steps 2-5, this time using 5% HCl as solvent.

FOR SOLID SAMPLES.1. Take 100 milligrams of each of the sample solids for testing and separately grind them well using a mortar and pestle.2. Put the ground samples separately in a clean and dry test tube. 3. Drop by drop, add 5% HCl by using the dry calibrated dropper.4. Note any change in color, warming effect, effervescence. Describe the solubility of the sample in the solvent used, depending on the number of drops of the solvent used to solubilize the sample being evaluated.5. Describe whether the sample was very soluble, soluble, slightly soluble or insoluble.6. If insoluble, repeat steps 2-5, this time using 5% NaOH as solvent.7. If soluble in 5% NaOH, repeat steps 2-5, this time using 5% NaHCO3 as solvent.8. If insoluble in 5% NaOH, repeat steps 2-5, this time using 5% HCl as solvent.

C. Reaction with litmus paper.If the compound tested is soluble in water, test the nature of the compound using red and blue litmus papers. Record the reactions observed.

D. Reaction with pH paper.If the compound tested is soluble in water, test the nature of the compound using pH paper. Record the reactions observed.

E. Ignition test.Place 10 drops of the liquid sample in a small evaporating dish and apply a lighted match to it. Do the same for the samples, except that they should be introduced to a lighted Bunsen burner.Observe if the sample tested is flammable or not.Observe the color of the flame and the presence or absence of soot.Observe also the burning time.

IDENTITY TESTS1. Ethanola. Mix 5 drops in a small beaker with 1 ml of KMnO4 T.S. Add 5 drops of 2N Sulfuric acid and cover the beaker immediately with filter paper moistened with a solution recently prepared by dissolving 100 milligrams of Sodium nitroferricyanide and 250 milligrams piperazine in 5 ml water: an intense blue color is produced on filter paper, the color becoming paler after a few minutes.

b. To 5 ml solution of (I in 10), add 1 ml of 0.1N NaOH then slowly (over a period of 3 minutes) add 2 ml of 0.1 N Iodine: odor of iodoform develop, and a yellow precipitate is formed within 30 minutes.

2. Phenol (USP 30)CAUTION! Avoid contact with the skin, since serious burns may result.

a. To a solution, add Bromine T.S. drop by drop: a white precipitate is formed dissolving at first, but becomes permanent as more of the reagent is added.

b. To 10 ml of the solution (1 in 100), add a drop of Ferric chloride T.S.: a violet color is produced.

3. Ethyl acetate (NF 25)It is easily volatilized even at low temperatures and is flammable; when burned, a yellow flame and an acetous odor is produced.

4. AcetonePhenylhydrazone test. All aldehydes and ketones readily form bright-yellow to dark-red 2,4-dinitrophenylhydrazones. Yellow derivatives are formed from isolated carbonyl groups and orange-red to red derivatives from aldehydes or ketones conjugated with double bonds or aromatic rings.Mix 5 ml of the test sample, acetone, in 0.5 mL of ethanol, and then add 0.75 mL of 2,4-dinitrophenylhydrazine reagent. Mix thoroughly and let sit for a few minutes. A yellow to red precipitate is a positive test.

Reagent: Dissolve 1.5 g of 2,4-dinitrophenylhydrazine in 7.5 mL of concentratedsulfuric acid. Add this solution, with stirring, to a mixture of 10 mL of water and 35 mL of ethanol.

Sodium nitroprusside Test. In a test tube, place 3 drops of acetone and 3 ml of water. Then add a drop of 3% NaOH. Add a few drops of glacial acetic acid and observe carefully the reaction.

5. FormaldehydePerform Phenylhydrazone Test using formaldehyde as the test sample.

6. TolueneBromine Testa. One ml of toluene is added to a clean and dry test tube. b. A few iron filings is added to another test tube, followed by one ml of toluene to rinse down any iron filings stuck on the test tube walls.c. To each test tube was added 3 drops of bromine.d. The test tubes were placed in a beaker of warm water for 15 minutes. The color of each test tube was observed, and whether or not HBr was evolved; and the results recorded.

Bayers Test (use of aqueous KMnO4)a. Five ml of KMnO4 solution is placed in one test tube.b. Five drops of toluene is added to the test tube.c. The test tube was shaken well for 1-2 minutes and the result noted.

7. Methanol CAUTION! Methanol is poisonous.Use identity tests for ethanol.

8. Isopropyl alcohol

9. Benzoic acid (USP 32)Prepare a saturated solution of benzoic acid in water, and filter twice. Take 5 ml portion of the filtrate and place it in a dry and clean test tube. Add Ferric chloride T.S.: A salmon-colored precipitate is formed.To a separate 10-mL portion of the filtrate, add 1 mL of 7 N sulfuric acid and cool the mixture: A white precipitate forms in 10 min; this precipitate is soluble in ether.

10. Salicylic acid (USP 30)It meets the requirements for the tests for salicylates:a. In moderately dilute solutions of salicylates, Ferric chloride T.S. produces a violet color.b. The addition of acids to a moderately concentrated solutions of salicylates produces a white, crystalline precipitate of salicylic acid that melts between 158 and 161C.

VI. Data and resultsUse Table 1 for preparing your pre-lab report starting with ethanol. Use additional rows for the rest of the compounds for testing.

Table 1. COMPARATIVE INVESTIGATION OF SOME ORGANIC COMPOUNDSCOMPOUNDSATTRIBUTESTHEORETICAL DATAACTUAL DATA

1. Ethanol and so on.Appearance

Color

Odor

Melting point

Boiling point

Solubility in:Water

5% NaOH

5% NaHCO3

5% HCl

VII. Answer to questions1. What is the USP definition of solubility?2. What is the USP definition of miscibility?3. Draw a diagram to show the solubility classification of organic compounds.4. Show the corresponding chemical reactions for the tests for ID performed on the sample compounds.IX. References usedhttp://opencourseware.kfupm.edu.sa/colleges/cs/chem/chem303/files%5C3-Lecture_Notes_CHEM-303_(Chapter_5).pdfNF 25/USP 30USP 32

Experiment 2.SYNTHESIS OF BENZOIC ACID

I. IntroductionBenzoic acid is a colorless, crystalline solid also known as benzenecarboxylic acid. It is the simplest aromatic carboxylic acid, with a carboxyl group (-COOH) bonded directly to the benzene ring. It is found naturally in the benzoin resin of a number of plants. Benzoin comes from the bark of a number of balsams of the Styrax genus, most notably Styrax benzoin and Styrax benzoides. S. benzoin is native to Southeast Asia, and was traded between Indonesia and China as early as the 8th century c.e. Benzoin was used for fragrances, spices, medicines, and incense. Today most benzoin comes from Sumatra (Indonesia) and Laos. Healthy trees do not produce benzoin, but an incision or wound injuring the cambium results in its secretion.CHEMICAL NAME = benzoic acidCAS NUMBER = 65850MOLECULAR FORMULA = C7H6O2MOLAR MASS = 122.1 g/molCOMPOSITION = C(68.9%) H(4.9%) O(26.2%)MELTING POINT = 122CBOILING POINT = 249CDENSITY = 1.3 g/cm3

II. ObjectivesThis experiment aims to:1. synthesize benzoic acid by oxidizing toluene with potassium permanganate; and2. characterize the resulting product using identified physico-chemical procedures

III. Materials and equipmentErlenmayer flaskgraduated cylinderbeakerDistilled water30-40% HClTolueneOxalic acid KMnO4pH paperSandbathplastic basinwater pump

IV. Special instructionsIce-cold water should be running on the condenser of the reflux set-up.Temperature must be controlled well, since over-heating might cause EXPLOSION.Porous boiling chips must be placed on the reaction flask.Do not leave your set-up unattended.

V. ProcedureA. Synthesis of the compoundA mixture of 5.0 ml toluene, 200 ml water and 8.6 grams of fine, potassium permanganate powder are placed in a 500 ml round-bottomed flask equipped with a condenser. The resulting mixture was allowed to undergo reflux for 4 hours with the use of a sandbath. CAUTION! Boiling chips made up of small pieces of broken ceramics should be added to the mixture to even out boiling thus preventing bumping.

Fig. 1 Reflux set-up. (The heat source is a sand bath, placed on top of a hotplate.)

Once the reaction is completed, the solution above the formed manganese dioxide precipitate must be colorless. If not, discoloration of the solution may be achieved by adding 1 ml alcohol or 0.5g oxalic acid while heating. This will quickly reduce the remaining potassium permanganate in the mixture.

The resulting solution is then filtered by suction or through a coffee filter and the obtained precipitate washed with hot water. The resulting filtrate is placed in a suitable beaker and the filtrate evaporated to about 50-100 ml with the use of a water bath and again filtered to remove the newly formed manganese dioxide. Wash the obtained solid with 5 ml of hot water and cool the combined filtrate to room temperature. The combined filtrate was acidified with concentrated HCl until it produces an acidic reaction to pH paper. The acidity of the reaction mixture will allow the formation of benzoic acid crystals from solution.

The mixture is filtered by suction and the crystalline material washed with cold water. The washed crystals are allowed to dry in-between layers of filter paper and finally weighed to determine the actual yield of the product.

Fig. 2. The chemical equation involved in the synthesis of benzoic acid

B. Identity tests for benzoic acid1. Prepare a saturated solution of benzoic acid in water, and filter twice. Take 5 ml portion of the filtrate and place it in a dry and clean test tube. Add Ferric chloride T.S.: A salmon-colored precipitate is formed.2. To a separate 10-mL portion of the filtrate, add 1 mL of 7 N sulfuric acid and cool the mixture: A white precipitate forms in 10 min; this precipitate is soluble in ether.VI. Data and results Accomplish the Report Sheet.

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Theoretical DataActual Data

Physical appearance

Melting point/Boiling point (as the case maybe)

Solubility

Yield

Percent yield

Tests for Identity

VI.Qestions to be answered:1.What is the mechanism of reaction involved in the preparation of benzoic acid?2.Give at least five (5) physico-chemical parameters used to ascertain the identity of benzoic acid. Include chemical reactions (if there is any)3.Identify the uses of benzoic acid.4.Provide plant sources where benzoic acid can be found.5.Give at least five official preparations where benzoic acid is an integral part of. For what are the named preparations used for. State where these named preparations are official.

VII. Reference usedMyers, R. L. (2007) The 100 Most Important Chemical Compounds: A Reference Guide.Greenwood Press: London.

Experiment. 3THREE-STEP SYNTHESIS OF SULFANILAMIDEI. INTRODUCTIONSulfa drugs were discovered in the early 1900s and were found to be active as antibacterial agents. Sulfanilamide inhibits the formation of folic acid in bacteria, thus inhibiting its growth and development due to non-formation of THFA (tetrahydrofolic acid), an essential compound in the development of the bacteria.Sulfanilamide is the common name for p-aminobenzenesulfonamide. The term sulfonamide indicates that it is an amide of sulfanilic acid. Sulfanilic acid (precursor of sulfonamide) can be prepared from aniline and sulfuric acid, and the name implies an aniline unit to which has been attached a sulfonic acid group. The names of the intermediates involved in the synthesis starting with the chlorosulfonation of acetanilide are all based from the parent compound.Sulfanilamide is a white, crystalline compound, having a molecular formula of C6H8N2SO2 used in the treatment of bacterial infections. The term sulfanilamide is also used to describe a family of molecules containing this functional group as exemplified by furosemide, a diuretic; sulfadiazine and sulfamethoxazole, for the treatment of urinary, respiratory and GIT infections.Sulfanilamide is easily synthesized from aniline in four steps:

II. OBJECTIVE: To synthesize sulfanilamide from aniline.III. INSTRUCTIONS:A. Read on the physical properties (physical appearance and melting point) of the intermediates and the product.B. Look for chemical tests that would identify the intermediates and the product. C. Read on techniques for heating, vacuum filtration, decolorization, crystallization and recrystallization, purification and melting point determination.D. Compute for the amounts (in grams or milliliters) of other reactants and reagents based on the amount of starting material that is assigned.E. At the end of the laboratory period, pass a datasheet complete with the computations of amounts of reactants, validated amounts, and actual results of physical and chemical tests.

IV. REAGENTS:AnilineConc. HClSodium acetateChlorosulfonic acidConc. HNO3Sodium bicarbonateDistilled waterAcetic anhydrideConc. AmmoniaIce water

V. REAGENT INFORMATION AND PRECAUTIONS:

COMPOUNDCHARACTERISTICS

Conc. HClIrritant, corrosive

Conc. AmmoniaHazardous gas, caustic and corrosive

AnilineIrritant to the eyes and skin, harmful if ingested and inhaled and a possible carcinogen

Sodium acetateIrritant to the eyes and skin

Chlorosulfonic acidCorrosive and reacts violently with water

Sodium bicarbonateIrritant especially to respiratory system

VI. PROCEDURE:A. Acetanilide1. Dissolve 1 gram of aniline in 30 ml of distilled water and I ml of conc. HCl in a 125 ml Erlenmayer flask. If the solution is colored, vacuum filter through decolorizing charcoal.2. Measure out 1.2 ml of acetic anhydride and prepare a solution of 1 gram of sodium acetate in 6 ml of distilled water.3. Add the acetic anhydride to the solution of aniline with stirring, and at once add the sodium acetate solution.4. Stir the mixture, cool it in ice, and collect and weigh the product acetanilide.NOTE: The material needs to be completely dry before the next step. Characterize the acetanilide.

B. p-Acetamidobenzenesulfonyl chloride1. Place 0.5 gram dry acetanilide in a dry 25 ml Erlenmayer flask.2. Add 1.25 ml of chlorosulfonic acid(Org13) (WARNING! Corrosive and reacts violently with water) a few drops at atime using a Pasteur pipette (CAUTION! No metal needles!).3. After about 10 minutes, the reaction should subside and almost all of the acetanilide should have dissolved.4. Heat the mixture in a hot water bath for about 10 minutes to complete the reaction.5. Pipet the mixture slowly with stirring into 7 ml of ice water in another 25 ml Erlenmayer flask (WARNING! USE EXTREME CAUTION WHEN DOING THIS!)6. Rinse the reaction flask with cold water and stir the product until an even suspension of white solid is obtained.7. Vacuum filter the p-acetamidobenzenesulfonyl chloride and wash it with water.

C. p-Acetamidobenzenesulfonamide1. Transfer the solid (you can use the solid even if it is wet) to the rinsed 25 ml Erlenmayer and add 1.5 ml of concentrated ammonia and 1.5 ml of distilled water.2. Heat the mixture to just below the boiling point on a hot plate with occasional swirling for 5 minutes.3. Cool the mixture in an ice bath and collect the p-acetamidobenzenesulfonamide by suction filtration and allow it to drain thoroughly.

D. Sulfanilamide1. Transfer the moist solid to a 25 ml Erlenmayer.2. Add 0.5 ml of conc. HCl and 1 ml of water.3. Boil the mixture gently until the solid dissolves and then continue heating at the boiling point for about 10 minutes longer (do not evaporate to dryness).4. Cool the solution to room temperature. No solid should deposit. If the solid material is seen, continue heating for a little while longer.5. To the cool solution, add a saturated aqueous solution of 0.5 grams of sodium bicarbonate until the solution is neutral to pH paper.6. Cool the mixture in ice and vacuum filter the sulfanilamide. Characterize the product.7. Calculate the percentage yield of your product.

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assuming 100% yield

Test for sulfanilamide

VII. Computations:1. Determine the theoretical yield of the intermediate and the product in your preparation.2. Calculate the percentage yield of your product using the formula:

Percentage yield = Actual yield x 100 Theoretical yield

VIII. Questions to be answered:1. What is the mechanism of reaction involved in the preparation of sulfanilamide?2. How are antibiotics usually prepared/obtained from natural sources?3. Provide chemical derivatives of sulfanilamide and for what are these derivatives used.Experiment 4: SYNTHESIS OF ASPIRINI. INTRODUCTIONHistorically, the salicylates were among the first drugs to achieve recognition as analgesics. In the 17th century, the extract of willow, Salix spirea, was found to produce fever-reducing properties and was used by Jesuit missionaries (Bailey, Jr. and Bailey 1998). In 1827, Leroux isolated salicin (I), the active principle in the willow bark and Piria, in 1838, prepared salicylic acid (II) from salicin. By 1860, Kolbe and Lautermann prepared it synthetically from phenol (Willette 1991). Although salicylic acid is an effective antipyretic, it causes severe stomach irritation in some people and for this reason the research for a pain reliever continued in the late 1800s (Bailey, Jr. and Bailey 1998). Aspirin, chemically known as acetylsalicylic acid, the salicylate ester of acetic acid, was first prepared in 1853 by Gerhardt, but remained obscure until Felix Hoffmann, who worked for the Bayer Company, discovered its pharmacologic activities in 1899 when he used the acetyl derivative on his father suffering from arthritis. The name aspirin comes from spirin, an old name of salicylic acid or spiric acid, derived from its natural source of spirea plants (Willette 1991). Unfortunately, even aspirin causes stomach distress in some individuals and minor, usually clinically unimportant, gastric or intestinal bleeding (Bailey, Jr. and Bailey 1998). Nevertheless, aspirin remains, until now, the most popular and the most versatile drug ever to have been synthesized.Salicylates, in general, exert their antipyretic action in febrile patients by increasing heat elimination of the body through mobilization of water and consequent dilution of the blood. This brings about perspiration, causing cutaneous dilatation. This does not occur with normal temperatures. The antipyretic and the analgesic actions are believed to occur in the hypothalamic area of the brain. Thye antitheumatic and antithrombotic actions of aspirin is said to arise from its selective action on the synthesis of the prostaglandin-related thromboxane and prostacyclin, which are counterbalancing factors involved in platelet aggregation and are released when tissue is injured (Willette 1991).Salicylcic acid is a bifunctional compound, having both a phenolic hydroxyl group and a carboxyl group at ortho positions of each other. Hence, it can undergo two different types of esterification reactions, acting either as the alcohol or the acid partner in the reaction. In the presence of a carboxylic acid or acid derivative, e.g. acetic anhydride, salicylic acid acts as the alcohol forming, for example, acetylsalicylic acid; whereas in the presence of alcohols, e.g. methanol, it forms esters such as methyl salicylate through its carboxylic group. Because salicylic acid has both the phenolic hydroxyl group and the carboxy of the product aspirinl group, polymers often complicate the esterification reaction. Fortunately, acetylsalicylic acid will react with sodium bicarbonate. This difference in the behavior will be utilized for the purification of the product aspirin (Pavia et al. 1976).The most likely impurity in the final product is salicylic acid itself, which can arise from incomplete acetylation or from hydrolysis of the product during the isolation steps. This material is removed during the various stages of the purification and in the final crystallization of the product. Salicylic acid, like most phenols, forms a highly colored complex with ferric chloride. Aspirin, which has this group acetylated, will not give the color reaction. Thus, the presence of this impurity in the final product is easily detected (Pavia et al. 1976).A simple method of the identification of aspirin is based on the principle that aspirin forms a beautifully colored blue complex with cupric acetate (Wilcox, Jr. and Wilcox 1995).II. OBJECTIVES:A. To demonstrate the process of esterification reaction;B. To understand electronic and steric effects in esterificaton reactions;C. To utilize the differing rates of reactions and differences in solubilities to optimize the yield of the desired product; andD. To utilize chemical tests in determining the presence of functional groups.

III. INSTRUCTIONS:

A. Read on the physical properties (physical appearance and melting point).B. Look for the theoretical results of each intermediate/product in the chemical tests given and read on the principle involved in each test.C. Read on techniques for heating, vacuum filtration, decolorization, crystallization and recrystallization, purification and melting point determination.D. Compute for the amounts (in grams or milliliters) of other reactants and reagents based on the amount of starting material that is assigned.E. Prepare a schematic diagram for the procedure.F. Draw the set-up necessary in the procedure. Label completely.G. At the end of the laboratory period, pass a datasheet complete with the computations of amounts of reactants, validated amounts, and actual results of physical and chemical tests.

IV. REAGENTS:Salicylic acidBenzeneAcetic anhydridePetroleum ether (optional)Conc. Sulfuric acid1% Ferric chlorideSaturated NaHCO3Cupric acetateConc. HCl95% EthanolV. PROCEDURE:

1. Weigh out 3.0 grams of salicylic acid and place it in a dried, 250 ml Erlenmayer flask.2. Measure 6.0 ml of acetic anhydride and add this to your flask. Be sure tho do this in the hood and wear your goggles. Dont let the acetic anhydride be in contact with your skin and dont let the vapors be in contact with your eyes.3. Carefully add 5 to 10 drops of 85% phosphoric acid, a catalyst, to the flask and swirl to mix everything thoroughly.4. Still in the hood, heat the mixture for about 10 minutes in a beaker of warm water (70-80 degrees)5. After heating, cautiously add 20 drops of distilled water.6. Remove the reaction set-up from the hood and then add 20 ml distilled water and cool in an ice bath. If crystals do not appear, scratch the walls of the flask with a stirring rod to induce crystallization. As soon the crystalline nuclei has appeared, stop the process and let he crystalline material form undisturbed. 7. Once crystallization is complete, filter the solid aspirin through a pre-weighed filter paper using a Buchner funnel. Wash the crystals with 2-3 ml of chilled water. The filtrate is mostly water and can be washed down the sink. Allow filtration to go through for about 15 minutes. Test for the presence of unreacted salicylic acid using the ferric chloride test below (Pavia et al. 1976). If the sample tests positive (violet colored solution), the crude aspirin is subjected to the recrystallization procedure as follows:Dissolve a small sample of the final product in a minimum amount of hot benzene, while gently and continuously heating the mixture on the steam bath. Caution: Benzene is a potential carcinogen. Handle it with great care. If any solid a remains, filter the solution by gravity through a fluted filter placed in a short-stemmed funnel w2hich has previously been pre-heated by pouring hot benzene through it. Let the filtered solution stand. On cooling to room temperature, the aspirin should crystallize. If it does not, add a little petroleum ether and cool the solution slightly in ice water, while scratching the inside of the glass with a glass rod. Collect the product by vacuum filtration. Repeat the ferric chloride test.8. Place the filter paper with the product in a watch glass and place it inside an oven at 100 degrees Centigrade for about 30 minutes until it is dry.9. Put the dry aspirin and the filter paper into an appropriate, pre-weighed container and weigh again.10. Calculate the weight of your final product. Determine the percentage yield of your product.CHEMICAL TESTSFerric chloride test. To a pinch of the crude product, add 1% ferric chloride solution and shake vigorously until the product is dissolved. Observe any changes in the color of the solution (Pavia et al. 1976)Hydroxamic acid test.Dissolve a small amount of the ester in a mixture of 1 ml of 0.5 N Hydroxylamine . (dissolved in 95% ethanol) and 0.2 ml of 6N Sodium hydroxide. Heat the mixture to boiling for a few minutes. Cool the solution and then add 2 ml of 1N Hydrochloric acid. If the solution becomes cloudy, add 2 ml of 95% ethanol to clarify it. Add a drop of 5% ferric chloride solution and note whether a color is produced. If the color fades, continue to add ferric chloride until it persists. A positive test should give a deep burgundy or magenta color (Pavia et al. 1976).Test for aspirin. In a 50 ml beaker, prepare a solution of 0.05 g of cupric acetate monohydrate in 10 ml of water that has been heated to about 55 degrees. In a 20 ml test tube dissolve 0.07 grams of acetylsalicylic acid in 1.25 ml of 95% ethanol and add the solution to the warm solution of cupric acetate. Stir the mixture well and set the test tube aside to cool slowly. Observe the formation of dark blue precipitate of cupric acetylsalicylate or cupric aspirinate (Wilcox, Jr. and Wilcox 1995). VI. DATA AND RESULT:

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assume 100% yield

Test/s for aspirin

VII. QUESTIONS TO ANSWER:1. What is the purpose of the concentrated acid in the acetylation reaction?2. Which would you expect to be a stronger acid: benzoic acid, salicylic acid, or aspirin? Explain.3. What is the purpose of concentrated acid in the purification of aspirin?4. How do the techniques of scratching and seeding induce crystallization?5. How is the ferric chloride test used to detect the presence of salicylic acid? What general type of compound gives a positive result for this test?6. Can you use water as solvent for recrystallization? Explain.

VIII. REFERENCES:

Bailey, P.S., Jr. and Bailey, C.A., 1998. Organic Chemistry: A Brief Survey of Concepts and Application. 5th Edition. Singapore: Prentice-Hall Internaional, 393-394.

Pavia, D.L., Lampman, G.M., and Kriz, G.S., Jr., 1976. Introduction to Organic Laboratory Techniques: A Contemporary Approach> Philadelphia: W.B. Saunders, 25-30, 423.

Wilcox, C.F., Jr. and Wilcox, M.F., 1995. Experimental Organic Chemistry: A Small Scale Approach. 2nd Edition. New Jersey: Prentice-Hall, 486-487.

Willette, R.E., 1991. Analgesic Agents. In: J.N. Delgado and W.A. Remers, ed. Wilson and Gisvold,s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 9th Edition. Philadelphia: J.B. Lippincott, 657.

Experiment 5: SYNTHESIS OF METHYL SALICYLATEI. INTRODUCTIONMethyl salicylate, also known as salicylic acid methyl ester, oil of wintergreen, betula oil, or methyl-2-hydroxybenzoate, is a natural product which can be obtained from several plant species. Some of the plants producing it are called wintergreens, hence its common name. Plants containing methyl salicylate produce this organic ester most likely as an anti-herbivore defense. If the plant is infested with herbivorous insects, the release of methyl salicylate may function as an attractant of beneficial insects that could act as natural predators for the herbivorous pests. Numerous plants produce the compound in very small amounts.It is used as a rubefacient in deep heating liniments, and in small amounts as a flavoring agent at no more than 0.04%. It is also used to provide fragrance to various products and as an odor-masking agent for some organophosphate pesticides. If applied in high quantities, it can cause stomach and kidney problems.It is one of the compounds that is attractive to males of various species of orchid bees, who apparently gather the chemical to synthesize pheromones; it is commonly used as a bait to attract and collect these bees for study.Methyl salicylate also has the ability to clear plant or animal tissue samples of color, and as such is useful for microscopy and immunochemistry when excess pigments obscure structures or block light in the tissue being examined. This clearing generally only takes a few minutes, but the tissue must first be dehydrated in alcohol.In pure form, methyl salicylate is toxic, especially when taken internally. The lowest published lethal dose is 101 mg/kg body weight in adult humans. It has proved fatal to small children in doses as small as 4 ml.Methyl salicylate can be produced by esterifying salicylic acid with methanol.II. OBJECTIVES:1. To synthesize methyl salicylate by the process of esterification.2. To know the requisites for the esterification reaction to occur.

III. REAGENTS:Salicylic acidMethanolConc. Sulfuric acidIV. REAGENT INFORMATION:

COMPOUNDCHARACTERIISTIC

Salicylic acid Irritant to the eyes and skin

MethanolToxic, CNS depressant

Sulfuric acidHighly corrosive chemical. May cause burns.

V. PROCEDURE:Place 1.0 gram of salicylic acid and 6.0 ml of methyl alcohol in a 25 ml Erlenmmayer flask. Add 4.0 drops of concentrated sulfuric acid (REMINDER! Note the odor of the resulting solution) and then place the test tube in a water bath previously heated to 7o degrees and heat the solution for 15 minutes.

NOTE: The boiling point of methanol is 64.6 degrees, care should be taken to avoiod overheating and minimize bumping.

Allow the resulting product to cool to room temperature and note the odor before placing it in a suitable container and properly label the product.

VI. DATA AND RESULT

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assume 100% yield

Test/s for aspirin

VII. QUESTIONS TO ANSWER:1. Give the general reaction for the synthesis of methyl salicylate.2. Propose a reaction mechanism for this synthesis.3. Provide the physico-chemical characteristics of the product.4. How can the product be tested by chemical means? Include pertinent chemical reactions.5. What physico-chemical methods can be resorted to, to identify methyl salicylate? Provide the characteristic IR and NMR spectra for this compound.

Experiment 6. DIAZOTIZATION AND SYNTHESIS OF AZO DYE, ORANGE II DIHYDRATE Experiment 7. SYNTHESIS OF METHYL ORANGEI. INTRODUCTIONAzo dyes, the most commonly employed of all kinds of dye can be prepared by azo coupling. This is due to the fact that aryl diazonium ions (ArN N+) are weak electrophiles and give strongly colored compounds (ArN=Nar) by electrophilic substitution, but only on aromatic rings which are strongly activated by hydroxyl or amino groups. Most dyeing operations utilize hot aqueous solutions of the dyes, many of which bear sulfonic acid groups to improve their water solubility. Two dyes will be prepared in this experiment. Sulfanilic acid will be diazotized by reaction with nitrous acid, and the resulting diazonium-sulfonate inner salt will then be coupled with 2-naphthol and N,N-dimethylaniline to give the dyes commonly known as Orange II and Methyl orange, respectively. II. REAGENTS:

For diazotization and synthesis of Orange II Dihydrate:Sulfanilic acid monohydrate2.5% aq. sodium carbonateSodium nitriteIceConcentrated HCl2-Naphthol10% aq. NaOH NaClDistilled waterEthanol

For the synthesis of Methyl Orange

N,N-dimethylanilineGlacial acetic acid10% aq. NaOHSaturated aq. NaCl

III. REAGENT INFORMATION:

COMPOUNDCHARACTERIISTIC

Sodium nitriteDecomposed even by weak acids with the evolution of brown fumes

Conc. HClIrritant; corrosive

N,N-dimethylanilinePoisonous!

Glacial acetic acidEye irritant

IV. PROCEDURES:

Procedure for diazotization of sulfanilic acid

Place 2.4 grams of sulfanilic monohydrate in a 125 ml Erlenmayer flask, and dissolve it in 25 ml of 25% aqueous sodium carbonate by boiling. Cool the solution in the flask with running water before adding 0.95 gram of sodium nirite with stirring to dissolve the solid. Pour the solution into a 50 ml Erlenmayer flask containing 12.5 grams of ice and 2.5 ml of concentrated hydrochloric acid. Within a few minutes the white diazonium sulfonate inner salt should form a suspension. Transfer half of it to a 100 ml beaker, and keep both containers cold until each is used in later steps.

Procedure for the preparation of Orange II dehydrate

Dissolve 0.9 gram of 2-naphthol in 5 ml of 10% aqueous sodium hydroxide in a 100 ml beaker. (It may be necessary to warm the mixture to dissolve the naphthol completely.) Chill the solution to bellow room temperature before adding the contents of the Erlenmayer flask containing the diazonium-sulfonate inner salt. Rinse the flask with a small amount of water, and add this to the beaker containing the 2-naphthol. The dye, as a sodium salt, forms rapidly. Stir the resulting paste thoroughly to ensure good mixing and, after 10 minutes, heat the mixture to dissolve all solids. Dissolve 2.5 grams of sodium chloride in this solution, heating if necessary. Then let the solution cool to room temperature undisturbed. Chill the solution in an ice bath for a few minutes with gentle stirring. Collect the product on a Buchner funnel. Since the filtration is slow, pour small portions into the funnel successively; then rinse the beaker with saturated aqueous sodium chloride.

Transfer the filter cake to a beaker, washing the filter paper and funnel with a small amount of water (about 12 ml). Then, dissolve the solid by heating the water at the boiling point, and filter through a Buchner funnel that has been pre-heated on a steam bath. Pour the filtrate into a 100 ml Erlenmayer flask, rinsing the filter flask with 1-2 ml of water. The total volume should not exceed 15 ml. Cool to 80 degrees before adding 25-30 ml of ethanol; then, set it aside to crystallize. Before collecting the product, chill the mixture thoroughly, and wash the crystals on the filter with a small amount of ethanol. Weigh the product and calculate the yield. (Orange II crystallizes as the dehydrate for which you must allow in the calculation of the yield.)

Synthesis of Methyl Orange

Thoroughly mix 0.8 ml of N,,N-dimethylaniline and 0.65 ml of glacial acetic acid in a small test tube. Dd this solution of dimethylanilinium acetate to the suspension of the diazoniumsulfonate inner salt in the 100 ml beaker, rinsing the test tube with a small amount of water. Stir the mixture thoroughly, and watch the red acid form of the dye separate, such that a stiff paste results, in 5-10 minutes. Add 9 ml of 10% aqueous sodium hydroxide to produce the orange sodium salt. Stir well, and heat the mixture to boiling, at which point most should be dissolved. Place the beaker in an ice bath and allow it to cool undisturbed.

Collect the product by filtration through a Buchner funnel using saturated aqueous sodium chloride to rinse the beaker and to wash the dark mother liquor from the filter cake.

Methyl orange is sometimes used as an acid-base indicator. To observe the color changes with pH, dissolve a few crystals in a small amount of water in a test tube, and add a few drops of dilute aqueous hydrochloric acid and then few drops of dilute aqueous sodium hydroxide to show that the color changes are reversible.

Determine the percentage yield for both azo dye products.

V. DATA AND RESULT

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assume 100% yield

Test/s for aspirin

VI. QUESTIONS TO BE ANSWERED:1. Draw the structure of methyl orange at acidic and basic pH, and underneath each structure, indicate the color observed for each compound.2. What are the methods of fabric dying?3. What are mordant dyes? Explain how mordant dyes adhere to fabrics.

Experiment 8: SYNTHESIS OF AMYL ACETATEI. INTRODUCTIONBanana oil is the common name of the chemical compound properly known as amyl acetate also known as isopentyl acetate. It is a colorless liquid ester derived from amyl alcohol. It resembles the smell of bananas but is not naturally found in banana fruit.

II. REAGENTS:Isopentyl alcoholGlacial acetic acidConc. Sulfuric acidDistilled water5% Sodium bicarbonateSaturated aq. NaCl solutionAnhydrous magnesium sulfate III. PROCEDURE:1. Place 15 ml of isopentyl alcohol in a 100 ml round-bottom flask and add 20 ml of glacial acetic acid.2. Swirl the flask and carefully add 4.0 ml of concentrated sulfuric acid (Caution! Highly corrosive).3. Attach a reflux condenser and, using a heating mantle, reflux the mixture for 1 hour (do not forget to add boiling chips). Cool to room temperature.4. Place the reaction mixture in a separatory funnel and add 55 ml of cold water (Remember to rinse the reaction flask with 10 ml of cold water and add it to the separatory funnel). Separate the lower aqueous layer.5. Extract the organic layer (upper layer) with 25 ml of 5% sodium bicarbonate solution twice (test to be certain that the aqueous layer is basic to litmus otherwise wash again). CAUTION! Formation of carbon dioxide which will exert pressure inside the separatory funnel.6. Extract the organic layer with 25 ml of water. Finally, add 5.0 ml of saturated aqueous NaCl to aid in layer separation (it removes traces of water from the organic layer). Do not shake this solution but simply swirl. Draw off the lower aqueous layer. Pour the top organic layer into an Erlenmayer flask and dry with 2 grams of anhydrous magnesium sulfate.7. Decant the ester into the distilling flask (make sure that the drying agent is excluded and all glassware completely dry). Set up the distillation apparatus. Be certain that the adapter is open to the atmosphere and that your thermometer is placed correctly in the distilling head(do not forget the boiling chips). Collect all distilled material but collect the fraction between 134 and 143 degrees in a separate tared flask. Keep the receiver flask cold to reduce the vapor escaping into the lab environment. Never distill to dryness. Record the barometric pressure in the laboratory.8. Weigh the product and calculate the percentage yield.

IV. DATA AND RESULTREPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assume 100% yield

Test/s for aspirin

V. QUESTIONS TO BE ANSWERED:1. Provide the chemical reaction involved in the synthesis of amyl acetate.2. Provide a possible reaction mechanism for the above synthesis to occur.3. Give reasons for the following steps:a. swirling of the flask containing the reactants prior to addition of sulfuric acid. b. washing with cold waterc. extraction of the organic layer with 5% sodium bicarbonate solution twiced. addition of 5 ml of saturated aqueous NaCle. keeping the receiver flask cold4. What are the uses of banana oil?5. Is banana plant a tree? Justify your answer.

VI. REFERENCES:http://bllogcritics.org/scitech/article/what-is-banana-oil/http://www.umsl.edu/orglab/experiments/Bananaoil.htmlhttp://www.hort.purdue.edu/newcrop/morton/banana.html

Experiment 9: PREPRATION OF AZELAIC ACID FROM CASTOR OILI. INTRODUCTIONCastor oil is a vegetable oil obtained from the castor bean. It is a colorless to very pale, yellow liquid with mild or no odor or taste. Castor oil is composed of a mixture of triglycerides, about 75% of which is tricinolein. The remainder consist of diricinoleoglycerides with the third acyl group, representing either oleic, linoleic, dihydroxystearic, or saturated (stearic or palmitic) acid.Azelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye and barley. It is a natural substance that is produced by Melassezia furfur, a yeast that lives on normal skin. It is industrially produced by the ozonolysis of oleic acid. It is effective against a number of skin conditions, such as mild to moderate acne, when applied topically in a cream population of 20%. Azelaic acid may be useful as a hair growth stimulant, although at present there is no clinical study to confirm the efficacy. Its antibacterial property reduces the growth of bacteria in the follicle (Propionibacterium acnes and Staphylococcus epidermidis). It has a keratolytic and comedolytic property which normalizes the disordered growth of the skin cells, lining the follicle. Azelaic acid does not result in bacterial resistance to antibiotics, reduction in sebum production, photosensitivity (easy sunburn), staining of skin or clothing, or bleaching of normal skin or clothing.II. OBJECTIVE OF THE EXPERIMENT: To prepare a useful chemical from a natural source.

III. PLANT SOURCE AND REAGENTS:Castor oil (unflavored)KOH pellets95% ethanolPotassium permanganateConc. Sulfuric acid

IV. REAGENT INFORMATION:

COMPOUNDCHARACTERIISTIC

95% ethanolToxic, CNS depressant

Conc. Sulfuric acidHighly corrosive chemical. May cause burns.

KOH pelletsCaustic irritant

V. PROCEDURE:Fifteen grams castor oil is added to a solution of 15 grams potassium hydroxide in 45 ml 95% ethanol. The mixture is placed in a 500 ml Erlenmayer flask equipped with a reflux condenser and is boiled for 30 minutes. Timing starts at the appearance of the first drop of condensate. The solution is then poured into 100 ml water and acidified by the addition of 30 ml of 40% sulfuric acid in water. The procedure is repeated until all the ricinoleic acid have been liberated. The acid that separates is washed until the aqueous layer becomes clear. The yield of crude ricinoleic acid thus obtained approximately 16 grams.Twelve grams of ricinoleic acid is dissolved in 80 ml water containing 4 grams potassium hydroxide. In a one liter round-bottomed flask equipped with a powerful mechanical stirrer are placed 34 grams of potassium permanganate and 400 ml water at 35 degrees. The mixture is stirred to facilitate solution of the permanganate, and, if necessary, heat is applied to maintain the temperature at 35 degrees. When the permanganate has completely dissolved, the alkaline solution of ricinoleic acid is added in single portion with vigorous stirring. The temperature rises to about 75 degrees. Stirring is continued for half an hour, or until a test portion added to water shows no permanganate color. To the mixture is now added a solution of 20 g concentrated sulfuric acid in 63 ml water. The acid must be added slowly and carefully to prevent too rapid evolution of carbon dioxide with consequent foaming. The mixture is heated on a steam bath for 10 minutes to coagulate the manganese dioxide, which is filtered while still very hot. After filtration, the manganese dioxide is placed in a 400 ml beaker and boiled with 50 ml water in order to dissolve any azelaic acid that may adhere to it. This mixture is filtered while hot, and the filtrate is added to the main portion. The combined filtrates are evaporated to a volume of about 200 ml and this solution is cooled in ice. The crystals that separate are filtered with suction, washed once with cold water, and dried. The yield is 3-4 grams material of melting point 95-106 degrees. The crude substance is dissolved in 60 ml boiling water, filtered with suction, and allowed to cool. The crystals are filtered, washed with water, and dried, the yield, 2-3 grams; melting point, 104-106 degrees.VI. DATA AND RESULT

REPORT SHEETExperiment No. and TitleName of the student/s:Date performed:Section and Group No.:Date submitted:

Starting material: ____________ gTHEORETICAL DATAACTUAL DATA

Physical appearance

Melting point

Solubility

Yield

Percent yield

Assume 100% yield

Test/s for aspirin

VII. QUESTIONS TO ANSWER1. Provide the chemical reactions involved in the preparation of azelaic acid from castor oil.2. Propose the mechanism of reaction involved based on the provided chemical reaction.3. Characterize castor oil. Provide the botanical origin of the plant source.4. Provide the names of 5 plant acids found in castor oil and give their chemical structures, as well as their IUPAC names.

IX. REFERENCES:

Bailey, P.S., Jr. and Bailey, C.A., 1998. Organic Chemistry: A Brief Survey of Concepts and Application. 5th Edition. Singapore: Prentice-Hall Internaional, 393-394.

Pavia, D.L., Lampman, G.M., and Kriz, G.S., Jr., 1976. Introduction to Organic Laboratory Techniques: A Contemporary Approach> Philadelphia: W.B. Saunders, 25-30, 423.

Wilcox, C.F., Jr. and Wilcox, M.F., 1995. Experimental Organic Chemistry: A Small Scale Approach. 2nd Edition. New Jersey: Prentice-Hall, 486-487.

Willette, R.E., 1991. Analgesic Agents. In: J.N. Delgado and W.A. Remers, ed. Wilson and Gisvold,s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 9th Edition. Philadelphia: J.B. Lippincott, 657.

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