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Practical Organic chemistry For Second Year chemistry Students By Dr.Baram AHMED Jaff Ph.D. Organic chemistry in University of Strasbourg I-Louis Pasteur2005 University Of Sulaimani
2009
2010 1
Practical Organic chemistry For Second Year chemistry Students By Dr.Baram AHMED Jaff Ph.D. Organic chemistry in University of Strasbourg I-Louis Pasteur2005 University Of Sulaimani
2009
2010
2
Content: No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Experiment name Safety in organic laboratory & Introduction Glass ware EXP.No. 1: Purification of organic–solids –by Sublimation EXP.No. 2: Determination of Melting point EXP.No. 3: Purification of organic chemistry –solid-by Re-crystallization EXP.No. 4: Determination of Boiling point EXP.No. 5: Purification of organic chemistry-liquids- by Distillation EXP.No. 6: Preparation of Cyclohexanol- Borohydride Reduction of 2-Methylcyclohexanone EXP.No. 7: Preparation of Methyl-Cyclohexene EXP.No. 8: Preparation of Cyclohexanone EXP.No. 9: Preparation of Aspirin EXP.No.10: Nucleophilic Substitution Reactions: Synthesis of tert--Butyl Chloride EXP.No.11: Ester Formation- preparation of Methyl SalisylateEXP.No.12: Preparation of Benzoic acid EXP.No.13: Preparation of Nitrobenzene EXP.No.14: Preparation of Aniline - By Reduction of nitrobenzene-
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EX.No.15: Preparation of Acetanalide
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EXP.No.16: Preparation of p-bromo Acetanalide EXP.No.17: Diazonium salt Reactions& preparation of methyl orange EXP.No.18: Properties of Aldehyde & ketones EXP.No.19: Preparation of Acetophenone-oxime EXP.No.20: Preparation f Phenyl Hydrazones EXP.No.21: Principles of Extraction : Extraction Of oil from sunflower seeds EXP.No.22: Extraction of Caffeine from tea leaves EXP.No.23: Principles of Chromatography EXP.No.24: Separation of Amino acid by paper chromatography Data Sheet References
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20 21 22 23 24 25 26 27 28
58 61 62 63 65 66 69 71 72
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LAB SAFETY RULES SAFETY APPAREL (WHAT TO WEAR!) In chemistry lab: (a)
You must ALWAYS wear protective eyewear that conforms to the ANSI Z87.11989 Standard for chemical splash hazard, which complies with OSHA 29CFR1910 regulations for eye and face protection. This means goggles, either non-vented or with indirect venting, or eye cup type glasses that form a seal over the eyes and conform to the contours of the face, protecting the eyes from splash, dust, or fumes. This type of eye protection is available through th e PJC bookstore.
(b)
You must always wear shoes in lab. The shoes must COMPLETELY cover the foot and must have sturdy soles (no sandals or open-toed shoes allowed.) Leather or vinyl shoes are highly recommended.
(c)
You must wear a full-length, chemical-resistant plastic apron in the laboratory,
(d)
You may NOT wear loose clothing in the lab, such as neckties, scarves, hats, and oversize sleeves (this type of clothing can easily be dragged or fall into a burner flame or beaker of chemicals).
(e)
While in the lab, long hair must be pinned up or otherwise restrained.
(f)
The use of chemical-resistant gloves is highly recommended when working with certain chemicals that may be absorbed through the skin and/or are suspected toxins, mutagens, carcinogens, or otherwise harmful agents.
SAFETY ENVIRONMENT Many accidents and injuries can be prevented simply by good housekeeping practices. (a)
Smoking is NOT permitted in the lab. (b) Open containers of food or drink may NOT be brought into the lab. Drinking and eating (including chewing gum) are NOT permitted in the lab. (c) Bring to the lab only those items that you need. Clutter increases the likelihood 4
of accidents! Store purses, briefcases, book bags, etc. in the center cupboards at each station during the lab; DO NOT LEAVE THEM ON BENCHES, ON TOP OF THE FUME HOODS, OR ON THE FLOOR ! (d) The trash cans are for PAPER TRASH ONLY! NEVER put broken glass or metal in a trash can! If you break something, notify the instructor or lab supervisor immediately. DO NOT ATTEMPT TO CLEAN UP THE BROKEN GLASS ITEMS YOURSELF! (e) Chemicals should be disposed of according to the written or verbal instructions for each chemical. NEVER put chemicals in the trash cans or glass disposal containers. (f)
In the event of a chemical spill, notify your instructor or the lab supervisor for directions and assistance in the proper clean-up of the spill.
SAFE WORK HABITS Perhaps the most important way to avoid accidents is to develop good, safe, working habits. (a)
NEVER put anything in your mouth while in the lab! Do not touch chemicals with your bare hands! Avoid contact with all chemicals, whenever possible, whether you think they are hazardous or not. If you get (or think you have gotten) any lab chemical(s) on your hands or elsewhere on you, rinse the effected area immediately and thoroughly with water and consult your instructor or the lab supervisor. Before leaving the lab, ALWAYS wash your hands THOROUGHLY!
(b)
ALWAYS read the label on a container both BEFORE and AFTER you remove a chemical from it. Make sure that both the SUBSTANCE and CONCENTRATION are correct.
(c)
Take only what you need from a container of reagent. If you accidentally take too much, DO NOT return the excess to the container! Instead, try to share it with your classmates or take the excess to the instructor or lab supervisor. NEVER put anything into a container of stock reagent!!!
(d) (e)
ALWAYS read the safety and disposal information posted in the lab that is provided for each reagent. If you are in doubt about how to dispose of a substance, ask the instructor or lab supervisor.
Follow written and/or verbal instructions EXACTLY on all experiments. DO NOT conduct any unauthorized experiments!! If you engage in unauthorized and/or careless work, you may be expelled from the lab, either for the day or permanently.
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When you need to look at something at eye level, bring the object UP to your eyes rather than bending down. When pouring, keep the container BELOW eye level. (h)
Use
flint
strikers to light burners. NEVER LEAVE A LIT BURNER Watch it yourself or, if necessary, request assistance from the lab instructor or lab supervisor. UNATTENDED!! !
(I)
NEVER leave a potentially dangerous situation (such as a reaction in progress) unattended. Watch it yourself or, if necessary, request assistance from the lab instructor or supervisor.
EMERGENCY PLANNING Despite all precautions accidents will still happen, and you need to plan what to do BEFORE the emergency arises: (a) In the event of any accident or injury, NO MATTER HOW MINOR, notify the lab instructor or lab supervisor. (b) Learn the location of all safety equipment--fire extinguishers, eyewash stations, showers, and fire blankets. (c)
Learn the location of the nearest telephone. In case of an accident or emergency, notify the lab instructor or lab supervisor AT ONCE. If you cannot immediately locate at least one of these staff members, call Public Safety at: X 2000 or X 2500, for a minor emergency. In the case of an extreme medical emergency (cardiac arrest, choking, allergic reaction, etc.) or other extreme emergencies (fire, explosion, etc.), immediately dial 9-911 first, followed by calling the PJC Police/Public Safety office at X 2500 or X 2000.
OTHER LAB RULES 1.
ALWAYS clean your work space before leaving the lab, to include wiping the bench top with a clean, damp sponge. Other students will be using the same space and common courtesy is necessary. Put all equipment from your drawer, back in your drawer before you leave, if you want to see it again! Thoroughly clean all equipment checked out of the stock room and returns it in the same condition that you received it! Make sure that all electrical equipment is turned off and unplugged, all water taps, gas and vacuum outlets are turned off before you leave the lab!
2.
You will not be held responsible for a broken item IF YOU REPORT IT TO THE INSTRUCTOR OR LAB SUPERVISOR. If you fail to report a broken item, lose an item, or if you fail to clean and return equipment checked out of the stockroom, a grade penalty may be assessed based upon the severity and frequency of the infraction.
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Glassware and apparatus
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Experiment No.1:- Purification of organic–solids –by Sublimation1 Sublimation of an element or compound is a transition from the solid to gas phase with no intermediate liquid stage. Sublimation is a phase transition that occurs at temperatures and pressures below the triple point (see phase diagram). At normal pressures, most chemical compounds and elements possess three different states at different temperatures. In these cases the transition from the solid to the gaseous state requires an intermediate liquid state. However, for some elements or substances at some pressures the material may transition directly from solid to the gaseous state. Note that the pressure referred to here is the vapor pressure of the substance, not the total pressure of the entire system. The opposite of sublimation is deposition. The formation of frost is an example of meteorological deposition.
Sublimation purification
Sublimation is a technique used by chemists to purify compounds. Typically a solid is placed in a vessel which is then heated under vacuum. Under this reduced pressure the solid volatilizes and condenses as a purified compound on a cooled surface, leaving the non-volatile residue impurities behind. This cooled surface often takes the form of a cold finger. Once heating ceases and the vacuum is released, the sublimated compound can be collected from the cooled surface. Usually this is done using a sublimation apparatus.
From Solid Liquid Gas Plasma
To Solid Solid-Solid Transformation Freezing Deposition -
Liquid
Gas
Plasma
Melting
Sublimation
-
N/A Boiling/Evaporation Condensation N/A Ionization Recombination/Deionization N/A
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Uses Frost-free freezers work by having a fan and air circulation inside the freezer. The sub-zero temperature combined with the air circulation that keeps the air arid significantly accelerates the sublimation process. This keeps freezer walls and shelves free of ice, although ice-cubes will continually sublimate. Dye sublimation is also often used in color printing on a variety of substrates, including paper. A small heater is used to vaporize the solid dye material, which then solidifies upon the paper. As this type of printer allows extremely fine control of the primary color ratios it is possible to obtain a good quality picture even with relatively low printer resolution, as compared to other printer types of similar resolution. Standard black and white laser printers are capable of printing on plain paper using a special "transfer toner" containing sublimation dyes which can then be permanently heat transferred to T-shirts, hats, mugs, metals, puzzles and other surfaces. In alchemy, sublimation typically refers to the process by which a substance is heated to a vapor, then immediately collects as sediment on the upper portion and neck of the heating medium (typically a retort or alembic). It is one of the 12 core alchemical processes. In the Fast-Freeze, Deep-Etch technique, samples (for example, tissue samples) are rapidly frozen in liquid nitrogen and transferred to a vacuum device in which surface ice is sublimed. This effectively etches the sample surface, revealing the preserved 3D structure of the hydrated material. A rotary shadowed surface replica can then be obtained via electron microscopy. Sublimation is also used to create freeze-dried substances, for example tea, soup or drugs in a process called lyophilization, which consists in freezing a solution or suspension and heating it very slowly under medium to high vacuum - specifically, a pressure lower than the vapor pressure of the solvent at its melting point. This can be well under the melting point of water if there are organic solvents or salts in the sample being freeze-dried. The resulting solid is usually much easier to dissolve or re-suspend than one that is produced from a liquid system, and the low temperatures involved cause less damage to sensitive or reactive substances.
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Experiment No.2:- Determination of Melting point
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Experiment No.3:- Purification of solid organic compounds by Re-crystallization
¶ Crystallization: Purification of Crude para-Anisic Acid Crystallization is the primary technique for the purification of compounds that are solids at room temperature. In the process of crystallization, molecules are deposited from a saturated solution and are selected, according to their shapes, to fit into growing crystal lattices. The technique can be carried out by dissolving a compound to be purified in a hot solvent (or solvent mixture) and then allowing the solution to cool. If the solvent or solvent mixture is properly chosen, the compound has a decreased solubility at lower temperatures, and it will form crystals in the solution. The purity of a solid, and therefore the success of or need for a crystallization procedure, is determined by taking a melting point. The melting point of a solid is defined as the temperature at which a solid and its liquid are at equilibrium. Practically, this temperature isn't observed as a ―point‖ but rather as a range with the lower temperature of the range noted when the first bit of liquid is seen and the higher temperature when the sample is entirely a liquid. As described in the Handbook, a melting point range of 2.0°C or less indicates that a substance is pure enough for most laboratory purposes. Since the melting point is a physical property of a compound, the melting point of a pure compound is useful in its identification. You will use crystallization to purify p-anisic acid: H3CO-C6H4-CO2H p-anisic acid
Summary of the Steps in a Crystallization Safety Precautions Ethanol is flammable; it is also toxic if ingested. Avoid breathing ethanol vapors by carrying out all experimental operations in your student hood.
Step 1 • Dissolve impure solid in minimum amount of hot solvent. • If the solution is not highly colored, and doesn’t contain insoluble impurities, go to step 4. • If the solution is highly colored, go to step 2. • If the solution has insoluble impurities, go to step 3. Step 2 Treat with decolorizing charcoal, then go to step 3. Step 3 Decant or gravity filter the hot solution, then go to step 4. Step 4 Allow to cool slowly, then go to step 5. Step 5 Chill on ice, then vacuum filter to isolate the crystals.
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Procedure Section (1) Dissolve the Compound Heat about 20 mL of ethanol in a small flask on a steam bath. (Have a boiling chip in the flask to ensure even boiling.) Obtain about 0.20 g of panisic acid from the ―crude p-anisic acid‖ jar in your lab. Weigh it and record the weight to the nearest hundredth of a gram. Sometime during the lab period, determine the melting point of a sample of crude p-anisic acid. Place your weighed, crude p-anisic acid in a 25 mL Erlenmeyer flask, add a boiling chip and 5 mL of the hot ethanol. Swirl the contents of the flask and heat the solvent-solid mixture to the boiling point using the steam bath. Intermittently add small portions of hot ethanol (about 1 mL), swirl, and heat to boiling until all soluble material has dissolved. You may need to use a glass rod to break up any chunks of undissolved material. (2) Remove Any Colored Impurities Remove the solution from the steam bath. Your solution of p-anisic acid will probably be colored. The color, in this case, is due to an impurity which you must remove. Therefore, add about 0.10 g of pelletized Norite to the solution. Swirl and heat the mixture for up to 5 min, or until the color disappears. If the solution is still colored after 5 min, add a little more Norite and repeat the process. (3) Remove Any Insoluble Impurities The Norite can now be considered an insoluble impurity and must be removed from the solution of dissolved p-anisic acid by transferring the liquid to another flask.This can be accomplished by one of three methods: 1 Carefully decant the clear liquid to a clean flask. 2 Transfer the clear liquid with a Pasteur pipet. 3 Hot filter the solution through fluted filter paper Whichever method you choose, keep the solution warm during the process by placing the receiving flask on your steam bath. (4) Crystallization
Remove the Erlenmeyer flask from the steam bath and allow the solution to cool, undisturbed, at room temperature. You will probably see crystals growing in the solution after several minutes. After 15 min, cool the flask in an ice bath (whether or not crystal growth is apparent). Place your Erlenmeyer used to heat ethanol in an ice bath to chill the solvent for use in the next step. (5) Vacuum Filtration
Isolate the crystals by vacuum filtration. Use chilled ethanol to wash the crystals. Allow the aspirator to suck air through the crystals for five min Transfer the crystals to a tared (pre-weighed) watch glass and allow to air dry for several minutes. Usually the filter paper can be lifted from the funnel with a spatula and then the crystals can be peeled from the paper in a single mass. Determine the weight of your purified p-anisic acid. Determination of Melting Point Determine the melting point of your purified p-anisic acid using either a Fisher-Johns ―hot stage‖ or a ―Mel-Temp‖ capillary melting point apparatus;
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Study Questions 1) A student crystallizes 5 g of a solid and isolates 3.5 g as the first crop. He/she then isolates a second crop of 1.2 g solid from the filtrate. a) What is the percent recovery in the first crop? b) What is the total percent recovery? 2) The solubility of acetanilide in hot and in cold water is given in the table below. What is the maximum percent recovery if 5.0 g of acetanilide is re-crystallized from 100 mL of water? solubility in 100 mL of water temperature 5.5 g 100°C 0.53g 0°C 3) What effect would each of the following operations have on the success of the crystallization of p-anisic acid from ethanol? Explain your answers. a) After Norite treatment, the hot solution containing the dissolved p-anisic acid is immediately placed in an ice bath. b) After crystallization has taken place, the cold solution is vacuum filtered and product crystals are collected on a Büchner funnel, then the crystals are washed with hot ethanol. c) After isolation of the p-anisic acid crystals on a Büchner funnel, they are washed with cold diethyl ether. 4) The CRC lists the melting point for a compound as 182-183°C. You observe a melting point for this same compound isolated in your experiment as 177-181°C.What can you conclude about the compound isolated in your experiment?
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Experiment No.4:- Determination of Boiling point
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Experiment No.5:- Purification of organic chemistry-liquids- by Distillation Distillation is the process of vaporizing a liquid, condensing the vapor, and collecting the condensed vapor (or condensate) in a different container. It is a general technique that permits liquid compounds to be purified or solvents to be removed from non volatile materials. Simple, fractional, steam, and vacuum distillation are four modifications of the basic distillation technique. If a perfect separation of two components A and B is achieved during a distillation, a plot of temperature vs. volume of condensate looks like the ideal graph (Figure 3.1). All of the lower boiling component A distills at its boiling point until it is removed from the mixture; then, the higher boiling component B distills at its boiling point. When separating mixtures of compounds with boiling points closer together than 100°C, completely ideal separations are not achieved. This is because the component B has an appreciable vapor pressure at the boiling point of component A. In a laboratory situation, one can plot the volume of distillate Vs temperature of the distilling vapor to determine how closely a distillation resembles an ideal separation.
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In this experiment, you will use the techniques of simple and fractional distillation to separate two liquids, n-pentane and cyclohexane. You will compare the efficiencies of the separations achieved in the two distillation techniques, both by monitoring the temperature of the condensing vapors as a function of the quantity distilled and by analyzing the composition of two or three samples of the distillate by gas chromatography.
Gas Chromatography: Gas chromatography (GC or GLC) is an important chromatographic technique used by the organic chemist. In the gas chromatograph an inert carrier gas constitutes the moving phase while a high-boiling liquid layer deposited on an inert solid support makes up the non-moveable component.
Safety Precautions: Cyclohexane and pentane are flammable. Do not distill to dryness, since it can lead to a potentially explosive situation.
Procedure: You are to distill 25 mL of a 1:1 (by volume) pentane-cyclohexane mixture. This lab takes two lab periods, the first period will be spent doing the simple distillation, the second the fractional distillation. Set up your apparatus as illustrated in Figure 3.2 (simple distillation) or Figure 3.3 (fractional distillation). Place a heating mantle under the round bottom flask. Plug the heating mantle into a Variac—never plug a heating mantle directly into an electrical outlet—but do not turn the Variac on yet. Use a 10 mL graduated cylinder as the receiving flask. The fractionating column, a condenser packed with glass beads. Place 25 mL of the pentane-cyclohexane mixture in the round bottom flask; don’t forget to add boiling chips to this flask. Set the Variac to 40, then turn on the Variac power. When the mixture begins boiling, adjust the Variac setting as necessary so that the distillate collects at a rate of 1 –2 drops/sec. As the distillation proceeds and liquid collects in the 10 mL graduated cylinder, record the temperature of the vapors at the distillation head as a function of the volumeof condensate (take a reading about every 1.0 mL). When 3 mL have been collected, remove the graduated cylinder and substitute it with a sample vial. Collect about 20 drops (0.5 mL); cap and save this sample for GC analysis. Then, put the 10 mL graduated cylinder back under the vacuum adaptor and continue collecting. Continue recording the temperature of the vapors every 1.0 mL. You may have to turn up the Variac if the distillation slows down during the process (try setting it to 60). When 15 mL (total; you will have to empty the 10 mL graduated cylinder once) have been collected, again remove the graduated cylinder and substitute it with a sample vial. Collect about 20 drops (0.5 mL); cap and save this sample for GC analysis. Again place the 10 mL graduated cylinder under the vacuum adaptor and continue collecting.
Discontinue the distillation after 20 mL have been collected or before the distillation pot is dry.Run GC samples as demonstrated by your TA or as shown in the film. 21
Experiment No.6:- Preparation of Cyclohexanol by
Borohydride Reduction of 2-Methylcyclohexanone The object of this experiment is to determine the structures and relative percentage yields of the products formed when 2-methylcyclohexanone is reduced with sodium borohydride. We also compare these results to predictions made using molecular mechanics and semiempirical molecular orbital calculations. In the reduction of 2-methylcyclohexanone, both the cis and trans isomers of 2-methyl cyclohexanol can be formed:
Examination of models reveals that the two cyclohexanols can, in principle, exist in four chair conformations:
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A molecular mechanics program can be used to calculate the relative energies of these four isomers and allow you to predict the most stable trans and cis conformations. Even without calculation, you should be able to predict which of the two trans conformations is the more stable.
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You can determine the structures and relative percentage yields of the products in this reaction using NMR spectroscopy. The 250-MHz 1HNMR spectrum of a 50/50 mixture of methylcyclohexanols is seen on the next page. The two lowest field groups of peaks are from the hydrogen atom on the hydroxyl-bearing carbon atom.
The reduction of 2-methylcyclohexanone with sodium borohydride will give a mixture of products, but not necessarily a 50/50 mixture. Integration of the two low-field groups of peaks will allow determination of the actual percentages of products in this reaction. But first, the peaks must be assigned to the cis and trans isomers. The groups of peaks have been expanded and numbered on the spectrum and the frequencies of the 11 peaks are listed in the caption. The NMR coupling constant of the proton on the hydroxyl-bearing carbon is a function of the dihedral angle between that proton and an adjacent vicinal proton. For example, the dihedral angle between HA and HB is 60°: This is seen most easily by examining molecular models. A Newman projection may also make this clear.
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The coupling constant for these two equatorial hydrogens, HA and HB, is usually in the range of 2 to 5 Hz.
The coupling of HA and HC (equatorial-axial) is usually in the range of 4 to 7 Hz, and the HD to HE coupling (diaxial) is in the range of 9 to 12 Hz. From this information, it should be possible to assign the groups of peaks at 3.1 and 3.8 ppm to either cis- or trans-2methylcyclohexanol. From the areas of the two sets of peaks, the relative percentages of the isomers can be determined.
Procedure – Borohydride Reduction of 2-Methylcyclohexanone To a centrifuge tube, add 2.5 mL of methanol and 600 mg (Look up the density to determine the volume needed. The volume is approximately 650L, NOT 2.5mL!) of 2-methylcyclohexanone. Using the Vortex mixer, mix the two liquids thoroughly. Cool this solution in an ice bath contained in a small beaker. While the reaction tube is in the ice bath, carefully add 100 mg of sodium borohydride to the solution. After the vigorous reaction has ceased, remove the tube from the ice bath, and allow it to stand at room temperature for 10 min, at which time the reaction should appear to be finished. To decompose the borate ester, add 2.5 mL of 3 M sodium hydroxide solution. To the resulting cloudy solution, add 1 mL of water. The product will separate as a small, clear upper layer. Remove as much of this as possible without getting any of the aqueous layer, place it in a small vial, and then extract the remainder of the product from the reaction mixture with one 1.5-mL portion of dichloromethane. Add the dichloromethane extract to the small product layer you already collected, and dry the combined extracts over anhydrous sodium sulfate (not calcium chloride). After a few minutes, transfer the solution to a weighed dry vial containing a boiling chip. Using a pipet attached to the water aspirator vacuum line to remove vapors, boil off the dichloromethane (and any accompanying methanol) in a hot water bath. Cap and label the vial. Run an infrared spectrum of the starting material and your product as a thin film to determine whether the reaction of the starting material has been complete. The infrared spectrum is shown below. Look for the appearance of the –OH stretching peak and the disappearance of the C=O stretching peak.
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Cleaning Up The reaction mixture is neutralized with acetic acid (to react with sodium borohydride) and flushed down the drain with water.
Computational Chemistry Using the computer program PC Model and following the instructions on the next page, calculate the steric energies of the conformers of cis- and trans-2-methylcyclohexanol. Each of these isomers has two principal conformations.
Report: You should turn in the attached data sheets with the labeled spectrum stapled to them.
Using PC Model 7 to Study Conformations of 2-Methylcyclohexanol 1. 2. 3. 4. 6. 7. 8. 9.
10. 11.
12.
Open PCModel 7 Click the Ring button. Click on the C6 button to insert a cyclohexane ring in the chair conformation. Hold down the right mouse button and rotate the structure to visualize the chair and easily see two adjacent carbon atoms in the ring. Click on the PT button to show the periodic table. Click the O atom on the periodic table and then click on an axial or equatorial hydrogen atom on the ring to change it into an oxygen atom. The bond should turn red. Click the C atom on the periodic table and then click on an axial or equatorial hydrogen atom on the ring to change it into a carbon atom. The bond should turn blue. Close the periodic table and click the H/AD button to turn the hydrogen atoms off and then back on again. The oxygen should now have a hydrogen atom attached and the carbon you added should have three hydrogen atoms attached. Click the Compute menu button and then the Minimize button to determine the molecule’s energy. To obtain the lowest energy conformation, you must move the H attached to the O to a position that minimizes the interactions with axial hydrogen atoms. Do this by using the Move tool to relocate the hydrogen away from the plane of the ring. First click the Move tool and then click on the H you wish to move. Then move the cursor to a position away from the ring plane and click the left mouse button again. You should then again Minimize the structure to get the energy of this new conformation. Record the MMX energy. Click Edit and then Erase to clear the screen and then repeat this procedure to determine the energies of the four possible chair structures for 2-methylcyclohexanol; 2 cis conformers and 2 trans conformers. (The cis isomer with the –OH group in the axial position and the methyl group in the equatorial position should have an energy of 9.705 kJ so you can check to see if you are doing it correctly).
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Experiment No.7 :- Preparation of methyl cyclohexene
Alkenes are often formed by elimination reactions as shown in the equation:
When X= a halogen, this reaction is called dehydrohalogenation; a strong base like KOH can bring about this elimination. When X=OH, the elements of water are lost and the reaction is called dehydration; this is usually acid-catalyzed. Whereas base-induced dehydrohalogenation usually follows a one-step mechanism (called E2 elimination), acid-catalyzed dehydration follows a two-step mechanism: the first step is loss of the X group (or the protonated X) generating a carbocation; the second step is loss of a proton from a carbon adjacent to the positive carbon, thus forming the alkene.
This is called E1 elimination . ―E‖ stands for elimination, in this case, the elimination of water; the ―1‖ stands for unimolecular, and indicates that only one molecule is involved in the rate-limiting step of the reaction, namely, the formation of the carbocation. This rate in turn is determined by the stability of the carbocation formed. Recall, the order of carbocation stability is 3°>2°>1°. Therefore, the relative rates increase in the order:
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If we are trying to dehydrate an alcohol the –OH group must first be transformed Into a better leaving group. This can be done by protonation; therefore, the reaction is carried out in acid solution:
The carbocation formed can undergo substitution as well as elimination—which process predominates depends on the experimental conditions. To suppress the substitution reaction, one uses a strong acid whose anion is a relatively poor nucleophile, such as H2SO4or H3PO4. Elimination is also favored by the use of a high reaction temperature. Finally, removing the product by distillation from the reaction mixture as rapidly as it is formed increases the yield of alkene. In this experiment, you will study the dehydration of 2-methylcyclohexanol by treating the alcohol with sulfuric acid and heat, then analyzing the product by GC. This dehydration might produce 1-methylcyclohexene, 3-methylcyclohexene, or a mixture of both:
According to Zaitsev’s rule, when HX is removed from a species to form an alkene, hydrogen is lost preferentially from the carbon atom, of those adjacent to the carbon atom bonded to X, that has fewer hydrogen’s. Thus, the E1 reaction preferentially produces the most substituted alkene product possible. This rule can help predict the product of many organic reactions, including the one above. However, an organic chemist cannot be certain whether a prediction he or she has made is accurate until the or she studies the reaction experimentally to find out whether or not it behaves in the expected manner. Your assignment in this experiment is to determine experimentally whether or not Zaitsev’s rule is followed in the dehydration of 2methylcyclohexanol. Reading:Organic Chemistryby Francis Carey, 7thed., pp. 196-205 (5.8-5.13).
Procedure Section Place 0.033 mole of 2-methylcyclohexanol in a 25 mL round bottom flask. Add slowly, with swirling, 2 mL of 9M sulfuric acid. Set up for simple distillation as in Figure 10.1. Distill slowly, at a rate of 1-2 drops/second or less (Variac 85-90), until approximately 2-3 mL has been collected, or until the distillation pot is nearly empty. Do not distill to dryness! Transfer the distillate to your separation funnel. Wash the distillate with two 2 mL portions of saturated aqueous sodium bicarbonate. Dry the organic layer over sodium sulfate (anh.) 28
*,
then determine the weight of the product mixture. Analyze the product mixture by Gas Chromatography (GC). Your gas chromatogram may show peaks for both 1and 3-methylcyclohexene; from the relative areas of these peaks, you can determine the percent composition of the product mixture. (Always use care when washing an acidic solution with NaHCO3. CO2 may be produced, causing pressure to build up in the funnel. Vent the funnel often ).
Study Questions 1) Below are three alcohols. Indicate which is dehydrated fastest and which slowest under reaction conditions similar to that given in the experiment above. Explain.
2) Where would starting material, methyl cyclohexanol, come out on a gas chromatogram relative to the methyl cyclohexene peaks? Explain. 3) Figure 10.2 shows two spectra, one of which is 2-methylcyclohexanol and one of which is 3-methylcyclohexene. Which spectrum belongs to which compound? Extra Study Questions 1) Draw the mechanism for the dehydration of 2-methylcyclohexanol, catalyzed by H2SO4, to form 1-methylcyclohexene. 2) A student dehydrated 4-methylcyclohexanol with sulfuric acid as outlined in the above experiment. He found that the product mixture included three alkenes, below. Explain his results.
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Experiment No.8:- Preparation of Cyclohexanone Compounds containing the ketone or aldehyde functional group are important in organic chemistry. They are common in nature and are often key intermediates in organic synthesis. Useful methods for preparation of ketones include the coupling of acid chlorides with organocopper reagents and the hydration of alkynes. Aldehydes can be prepared by reduction of acid chlorides with certain metal hydrides or by catalytic hydrogenation. However, the most important method for preparation of both ketones and aldehydes is the oxidation of alcohols. Alcohols are among the most readily available organic compounds, and therefore, this method for preparation of aldehydes and ketones is extremely useful.
Primary and secondary alcohols are oxidized to the corresponding aldehydes and ketones by various oxidizing agents, e.g., dichromates,t-butyl hypochlorite, hypochlorous acid, potassium permanganate, and nitric acid. The aldehydes derived from primary alcohols can be further oxidized to carboxylic acids by some of these oxidizing agents (including HOCl), while the ketones derived from secondary alcohols are stable to further oxidation. The most widely used oxidizing agent is chromic acid, which is prepared by mixing sodium dichromate with sulfuric acid. However, chromium salts are suspected mutagens and carcinogens, and strict EPA regulations exist for the handling and disposal of chromium compounds. Hypochlorous acid (HOCl), an alternative oxidizing agent, is readily available, inexpensive, safe, and environmentally sound as compared to the dichromates. Although HOCl is unstable and decomposes slowly to upon storage, it can be prepared from a common household item: bleach. Household bleach contains sodium hypochlorite which, when treated with acetic acid * , produces the active oxidizing agent:
* Acetic acid is a component of another household item, namely, vinegar. Vinegar contains 4-5% acetic acid.
In this experiment, a mixture of bleach and acetic acid will be used to prepare cyclohexanone from cyclohexanol (Chapman-Stevens Oxidation).
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The mechanism for this reaction has not been fully established, although the following seems likely:
In order for the reaction of hypochlorous acid and cyclohexanol to go to completion, the hypochlorous acid must be in excess during the reaction. Since the concentration of hypochlorite in household bleach varies, the presence of excess hypochlorous acid cannot be assumed by adding an excess based on the molar amount of cyclohexanol and assuming household bleach to be 5.25% sodium hypochlorite. Instead, the presence of hypochlorous acid must be established by a chemical test, the potassium iodide-starch test. This test employs paper impregnated with iodide ions and starch (KI-starch test paper); a drop of the reaction mixture is placed on the paper. If hypochlorous acid is present, it oxidizes the iodide ion in the test paper to iodine, which in turn forms a blue-black complex with the starch in the test paper: To determine if enough bisulfite has been added, the reaction mixture is again tested with KI-starch test paper, this time, the absence of hypochlorous acid is the desired result. After neutralization with sodium hydroxide, the cyclohexanone is ―salted out‖ by adding solid NaCl. Salting out is a common organic chemistry practice, based on the principle that dissolved inorganic salts decrease the solubility of most organic compounds in water. The cyclohexanone is extracted into methylene chloride and the resulting solution treated with drying agent and heated to evaporate off the methylene chloride. High purity cyclohexanone could then be obtained by distilling the product, a method which would also help to identify the product by giving the boiling point. You will not have time to distill the product. Instead, you will run an IR of your product. The IR will indicate both the identity and the purity of your cyclohexanone.
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Procedure Section Place 10 mmoles of cyclohexanol and a stir bar in an Erlenmeyer flask. Place over a stir motor and stir while you carefully add 2.5mL of acetic acid (conc.). Place 15mL of bleach (approximately 5.25% sodium hypochlorite *) in your separation funnel, position the separation funnel above the Erlenmeyer flask, and add the bleach drop wise to the cyclohexanol/acetic acid mixture. The addition of bleach should take about 15 min. If the reaction flask becomes hot to the touch during the bleach addition, use an ice bath to cool it down. When the addition of the bleach is complete, the solution will be pale yellow to yellow-green in color. Test the solution for excess hypochlorous acid and, if necessary, add additional bleach. Stir the reaction mixture for an additional 15 min at room temperature. Then, quench excess oxidant by adding 10-20 drops of saturated sodium bisulfite solution.†Test for excess hypochlorous acid and, if necessary, add additional sodium bisulfite. Add 2 drops of thymol blue (an indicator), then add 6N NaOH until the solution is just basic (the indicator will turn light blue). Add solid NaCl until the solution is saturated with salt, then decant the liquid into your separatory funnel. Extract with 5 mL of methylene chloride, save the organic layer, then extract the aqueous layer one more time with 5 mL of methylene chloride. Caution: if the aqueous layer is warm, a lot of pressure can build up in the separation funnel when it is shaken with methylene chloride. Be sure to vent your separation funnel frequently during the extraction. Combine the organic layers and dry over anhydrous sodium sulfate. Filter or decant to remove the drying agent. Remove the methylene chloride from the solution either by evaporating it on a steam bath (do not forget to add a boiling chip!) or by placing it in a side arm flask, stoppering it, and applying vacuum until bubbling is no longer apparent.
* Sodium hypochlorite (NaOCl) is available only in solution. A 5.25% aqueous solution is 5.25 grams of NaOCl in a total volume of 100 mL. † Saturated sodium bisulfite is approximately 30 grams of sodium bisulfite in 100 mL of water.
Study Questions 1) If a procedure requires 10.0 g of HOCl, how many mL of 20% (aq.) NaOCl are needed? (Hint: see the footnote in the Procedure section that defines ―%‖ solutions.) 2) Each of the compounds below is treated with hypochlorous acid (HOCl) as you will do in this experiment. For each compound, give the structure of the product of the reaction or, if no reaction occurs, write ―No Reaction.‖
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3) The 1H-NMR spectra of cyclohexanol and cyclohexanone are given in Figure above Identify which spectrum belongs to which compound and assign the peaks in each spectrum that substantiate your decision.
4) In the past, students have found that our procedure for the oxidation of cyclohexanol produces not only cyclohexanone, but also a small amount of cyclohexene. a) In an IR spectrum, where are IR bands that represent alkene compound stretches? b) How would the 1H-NMR of cyclohexene differ from that of cyclohexanone?
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Experiment No.9:- Preparation of Aspirin Aspirin is among the most fascinating and versatile drugs known to medicine, and it is among the oldest — the first known use of an aspirin-like preparation can be traced to ancient Greece and Rome. Salicigen, an extract of willow and poplar bark, has been used as a pain reliever (analgesic) for centuries. In the middle of the last century it was found that salicigen is a glycoside formed from a molecule of salicylic acid and a sugar molecule. Salicylic acid is easily synthesized on a large scale by heating sodium phenoxide with carbon dioxide at 150°C under slight pressure (the Kolbe synthesis):
Unfortunately, however, salicylic acid attacks the mucous membranes of the mouth and esophagus and causes gastric pain that may be worse than the discomfort it was meant to cure. Felix Hoffmann, a chemist for Friedrich Bayer, a German dye company, reasoned that the corrosive nature of salicylic acid could be altered by addition of an acetyl group; and in 1893 the Bayer Company obtained a patent on acetylsalicylic acid, despite the f act that it had been synthesized some 40 years previously by Charles Gerhardt. Bayer coined the name Aspirin for its new product to reflect its acetyl nature and its natural occurrence in the Spiraea plant. Over the years they have allowed the term aspirin to fall into the public domain so it is no longer capitalized. The manufacturers of Coke and Sanka work hard to prevent a similar fate befalling their trademarks. In 1904 the head of Bayer, Carl Duisberg, decided to emulate John D. Rockefeller's Standard Oil Company and formed an "interessen gemeinschaft" (I.G.) of the dye industry (Farbenindustrie). This cartel completely dominated the world dye industry before World War I, and it continued to prosper between the world wars, even though some of its assets were seized and sold after World War I. After World War I an American company, Sterling Drug, bought the rights to aspirin for $5.3 million. Sterling was bought by Eastman Kodak in 1988, then sold to SmithKline Beacham. Because of their involvement at Auschwitz, the top management of I.G. Farbenindustrie was tried and convicted at the Nuremberg trials after World War II, and the cartel broken into three large branches—Bayer, Hoechst, and BASF (Badische Anilin and Sodafabrik)—each of which does more business than DuPont, the largest American chemical company. In 1997 the merican rights to the Bayer name and trademark were sold back to Bayer A.G. for $ I billion. By law, all drugs sold in the United States must meet purity standards set by the U.S. Food and Drug Administration (FDA), and so all aspirin is essentially the same. Each five-grain tablet contains 0.325 g of acetylsalicylic acid held together with a binder. The remarkable difference in price for aspirin is primarily a reflection of the advertising budget of the company that sells it. Bayer has 5% of the painkiller market; lower-priced generic aspirin has 18%.
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Aspirin is an analgesic (painkiller), an antipyretic (fever reducer), and an antiinflammatory agent. It is the premier drug for reducing fever, a role for which it is uniquely suited. As an anti-inflammatory, it has become the most widely effective treatment for arthritis. Patients suffering from arthritis must take so much aspirin (several grams per day) that gastric problems may result. For this reason aspirin is often combined with a buffering agent. Bufferin is an example of such a preparation. The ability of aspirin to diminish inflammation is apparently due to its inhibition of the synthesis of prostaglandins, a group of C-20 molecules that enhance inflammation. Aspirin alters the oxygenase activity of prostaglandin synthetase by moving the acetyl group to a terminal amine group of the enzyme. If aspirin were a new invention, the FDA would place many hurdles in the path of its approval. It has been implicated, for example, in Reye's syndrome, a brain disorder that strikes children and young people under 18 who take aspirin after flu or chicken pox. It has an effect on platelets, which play a vital role in blood clotting. In newborn babies and their mothers, aspirin can lead to uncontrolled bleeding and problems of circulation for the baby— even brain hemorrhage in extreme cases. This same effect can be turned into an advantage, how-ever. Heart specialists urge potential stroke victims to take aspirin regularly to inhibit clotting in their arteries, and it has been shown that one-half tablet per day will help prevent heart attacks in healthy men. Aspirin is found in more than 100 common medications, including Alka-Seltzer, Anacin, Coricidin, Excedrin, Midol, and Vanquish. Despite its side effects, aspirin is one of the safest, cheapest, and most effective nonprescription drugs, although acetaminophen (Tylenol, etc.) has 40% and ibuprofen (Advil, etc.) has 26% of the painkiller market in dollar volume ($2.47 billion in 1996). Naproxen (Aleve) has 6% of the market. Aspirin is made commercially employing the same synthesis we will use. The reaction can be summarized:
The mechanism of the reaction is:
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Procedure: Prepare a hot water bath (80° – 100°C) before beginning this procedure. In a DRY 50 mL Erlenmeyer flask place 1.0 g of salicylic acid and carefully add 2 mL of acetic anhydride (Acetic anhydride must NOT be allowed to come into contact with water or your skin!). Mix and add 3 drops of concentrated phosphoric acid. Swirl again to thoroughly mix the reactants. Clamp the flask into place in the hot water bath and heat for 15 minutes. All of the salicylic acid may not dissolve until the reaction flask is heated. You also may need to use a stirring rod to help break up the pieces of salicylic acid. Leave the stirring rod in the flask during the reaction. Raise the flask out of the hot water bath and, while it is still warm, very carefully add about10 drops of water one drop at a time, swirling the flask after each addition. You must be very careful not to add the water too rapidly as it reacts vigorously with the unreacted acetic anhydride releasing enough heat to cause the liquid to boil and splatter. (Keep the hot water bath hot (90°+) for the purification later.) After the 10 drops of water have been added, add an additional 10 mL of water and allow the flask to cool. Crystallization should start at this point. Place to flask into an ice bath
to facilitate crystallization. If the product does not crystallize, either scratch the inside of the flask with a glass rod or add a seed crystal of aspirin to initiate crystallization. Collect the solid by vacuum filtration and wash it with a few milliliters of COLD water. Save a few crystals for MP determination and save about 10mg for analysis. Purify the crude product by recrystallization using the method described below. Add the solid to be re-crystallized to a large test tube and add 7.0mL of 95% ethanol. Place the tube in the hot water bath until the ethanol begins boiling. If all the crystals are not dissolved add small increments of ethanol (keep track of how much you add) until all crystals are dissolved in the boiling ethanol. Once all of the crystals are dissolved, add an additional 6-8 drops of ethanol. Estimate the total volume of ethanol used. Add 14mL of warm water (~60°C) to the solution while it is still at the boiling point, and swirl to mix. If any precipitate forms, heat the solution gently until it is clear but do not boil. Remove the tube from the hot water and allow it to cool slowly to room temperature. Induce crystallization, if necessary, and place the tube in an ice-water bath to complete crystallization. Collect the purified product by vacuum filtration and wash the product with a few milliliters of ice-cold water. Save another small sample of the aspirin in a clean, labeled test tube for analysis. Dry and weigh the remainder of the product. Press the wet product between 2 pieces of filter paper and then dry in the drying oven before determining yield and obtaining the IR spectrum. The IR spectrum of aspirin is shown on the next page. To another test tube, add about 10 mg of salicylic acid and place in a rack with the sample saved from your product. Dissolve each in 0.5 mL of 95% ethanol. Add a drop of 36
aqueous 2.5% iron (III) chloride (ferric chloride) to each tube and record your observations. What reaction occurs with iron (III) ions and salicylic acid? Does it occur with aspirin? Why? If time permits, perform TLC on your crude and purified products. Dissolve a small amount of the products, a sample of pure aspirin and a sample of salicylic acid in 95 % ethanol. Spot the plate with salicylic acid, the aspirin standard, your crude product and your purified product. Develop and visualize as you did in the TLC lab earlier. The developing chambers should be already prepared with the proper solvent. The IR spectrum of acetylsalicylic acid:
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Experiment No.10- Nucleophilic Substitution Reactions:
Synthesis of tert--Butyl Chloride Technique: Extraction Alkyl halides can be prepared from alcohols by reacting them with a hydrogen halide,HX(X=Cl,Br, orI). The mechanisms of acid-catalyzed substitution of alcohols are termed SN1 and SN2, where ―S‖ stands for substitution, the ―N‖ stands for nucleophilic, and the ―1‖ or ―2‖ for unimolecular or bimolecular, respectively. Secondary alcohols react with hydrogen halides by both SN1 and SN2 mechanisms, primary alcohols by SN2 and tertiary alcohols by SN1. The order of reactivity of alcohols towards hydrogen halides (HX) is:
Tertiary alcohols react readily with HX alone to form the alkyl halide, while secondary and primary alcohols require the presence of zinc chloride or heat. Let's examine the mechanisms of both S N1 and SN2 reactions to see why this is so:
In an SN1 reaction, the protonated alcohol, or oxonium ion, loses a water molecule to form a carbocation intermediate in the rate-determining step. The carbocation is then rapidly attacked by the halide ion (X-) to form the alkyl halide. Since tertiary alcohols form more stable carbocation intermediates than do primary and secondary alcohols, tertiary alcohols are the most likely to follow the SN1 pathway.In an SN2 reaction, the nucleophile (X-) assists in the expulsion of H2O from the oxonium ion via a bimolecular
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transition state. The SN2 process is expected to be especially slow (and is in fact not observed) for tertiary alcohols since the transition state will be particularly crowded; as the degree of substitution decreases at the reacting center the rate of the S N2 process becomes greater and the rate of the SN1 process decreases (vide supra ). Consequently, the SN2 process is the predominant one for primary alcohols. In SN1 reactions, the formation of a carbocation can lead to rearrangements. Also, elimination to form an alkene can occur. In this experiment you will prepare 2-chloro-2-methyl propane * from 2-methyl-2- propanol, using HCl as the hydrogen halide:
The presence of a tertiary alkyl halide can be determined by reacting a small amount of your product with a solution of silver nitrate (AgNO3 ) in ethanol. Tertiary alkyl halides ill react rapidly via an SN1 mechanism with the AgNO3 to form a precipitate of AgCl:
To promote the above SN1 reaction, a highly polar solvent (ethanol) is used to dissolve the alkyl halide. The chloride will ionize (if it can) to the alkyl cation and chloride ion. The cation will react with the alcohol solvent to form the ether and HCl. In this case both products are soluble; however, if silver ion is present in the solution, insoluble AgCl will form and a precipitate will be visible. Primary halides do not react in this test, and secondary halides react only slowly with heating. Safety Precautions Concentrated hydrochloric acid is corrosive and a poison — wear gloves and protective clothing while handling this reagent. Hydrochloric acid is rated as a poison. Both the alcohol and the alkyl halide are flammable.
Procedure Section Put 5 mL of 2-methyl-2-propanol (t -butyl alcohol) in an Erlenmeyer flask, place the flask over a stir motor, add a stir bar, and commence stirring. Cautiously add 13 mL of concentrated HCl (12N). Stir the reaction mixture for 15 min. Transfer the mixture to your separatory funnel and allow standing until two clear layers have separated. Remove the
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aqueous layer, then wash the organic layer, first with 6 mL of saturated aqueous sodium chloride solution, then with 6 mL of saturated aqueous sodium bicarbonate, and finally with another 6 mL of saturated aqueous sodium chloride. Save the organic layer. The reaction between the residual HCl and the sodium bicarbonate will give off a substantial amount of carbon dioxide. Care must be taken NOT to confine this gas in the funnel. Swirl the mixture initially in the UNSTOPPERED, upright funnel, then invert the funnel and vent IMMEDIATELY into your student hood. Finally, shake the funnel gently and briefly between periods of venting until the evolution of gas subsides. Dry the organic layer over CaCl2 (anh.) * . Weigh or measure the volume of your product to determine your yield. Run an IR spectrum of your product and do the silver nitrate test (below). Silver Nitrate Test for Alkyl Halides: Place a few drops of your product in a small test tube. Add 2 drops of the silver nitrate test solution and mix. The appearance of a white precipitate indicates that a reaction as taken place between the alkyl halide and silver nitrate. Dispose of the test reaction in the small organic waste jar in the main hood. Wastes Aqueous Waste: HCl layer from first separation, the sodium bicarbonate wash, and the two sodium chloride washes. Used Drying Agent: Place spent drying agent in the small trash receptacle labeled ―used drying agent‖ in the main hood.Organic Waste Jar : Test reactions. Recovery Jar: Product, 2-chloro-2-methylpropane.
This compound can be found in the CRC as either 2-chloro-2-methyl propane or as tert –butyl chloride (listed in alphabetical order as butyl chloride, - tert ). Remove the drying agent either by gravity filtration or one of the methods shown in Figure
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Experiment No.11:- Ester Formation- preparation of Methyl SalisylateCarboxylic acid esters have the general formula RCO2R', where R and R' may be an alkyl or an aryl group. Some esters are flavoring or odor concentrates, while others have medicinal uses. As you will see in this experiment, small changes in the structure of an ester molecule profoundly influence its odor and flavor. Carboxylic acid esters may be formed by the direct reaction of a carboxylic acid with an alcohol. Such a reaction is called an esterification reaction ; it is both acidcatalyzed and reversible:
The acid catalyst (generally a mineral acid) protonates the carbonyl group of the acid making it more readily attacked by the nucleophilic oxygen of the alcohol. A molecule of water is then eliminated and the ester is formed. At reflux temperatures and in the presence of an acid catalyst, both the forward and reverse esterification reactions are rapid and the system comes to equilibrium within a few minutes. In order to obtain a high yield of ester, the equilibrium must be shifted toward the products. One technique for accomplishing this is to use a large excess of one of the reagents (the cheaper one). Another method is to remove one (or more) of the products as it informed (e.g., azeotropic distillation of water). If the alcohol or the acid contains bulky substituent’s, the acid-catalyzed esterification may be very slow or may not occur at all due to steric hindrance. In such cases, conversion of the acid to its acid chloride permits a facile reaction with the alcohol. The position of equilibrium is determined by the equilibrium constant (K), as defined by the following mass-action expression:
The equilibrium constants for the formation of different esters of acetic acid from the corresponding alcohols in the presence of an acid catalyst are given in the table below. The K values were determined experimentally from systems at equilibrium and may be taken as a measure of the efficiencies of the esterification processes. For example, the values indicate that N -butyl acetate (K = 4.24) is prepared much more efficiently than is t-butyl acetate K = 0.0049). These data also indicate that primary alcohols are comparatively easy to esterify, while secondary alcohols are esterified with some difficulty, and tertiary alcohols hardly react.
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Your TA will assign to you the preparation of one of four esters: isoamyl acetate, octyl acetate, n-butyl propionate, or n-butyl acetate. The primary alcohols employed in these syntheses are only about two-thirds converted into their esters at equilibrium. The preparations involve carrying out the reactions to equilibrium followed by isolation and purification of the ester products.
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Procedure Section During the Identification of an Unknown experiment: Mix 0.05 moles of the alcohol and 0.125 moles of the corresponding carboxylic acid in an Erlenmeyer flask. carefully add 1 mL of concentrated sulfuric acid and gently swirl the flask to mix the contents. Stopper the flask and wrap with parafilm; place it in a safe place in your drawer until the next lab period. During the scheduled Esterification lab period: Pour the contents of the reaction flask into your separatory funnel. Rinse the flask with both 12 mL of methylene chloride and 10 mL of water and add these rinses to the separatory funnel also. Shake, then separate the aqueous and organic layers: if two layers are not visible, add 10 mL of water to the separatory funnel. Be sure that you know which is the aqueous and which is the organic layer. Solutions of concentrated acid can be denser than methylene chloride. Re-extract the aqueous layer with another 12 mL of methylene chloride. Combine the organic layers and wash them two times with 8 mL of 10% Na 2CO3. Dry the organic layer over anhydrous sodium sulfate. Swirl the mixture intermittently over a ten minute period, then allow the sodium sulfate to settle and decant the organic layer into a clean and dry container. The organic layer contains the product, possible starting materials, and about 25 mL of methylene chloride. To expedite the isolation of pure ester, you can first remove the 25 mL of methylene chloride under reduced pressure using either a rotary evaporator (roto-vap) or the vacuum system: • Roto-vap: Place your sample in a 100 mL round bottom flask. Your TA will show you how to use the roto-vap. • Vacuum system: Place your sample in a side-arm flask; do not fill the flask more than about one-third full. Stopper the flask and use the vacuum system to remove the methylene chloride. Whichever method you employ, discontinue the process when the liquid in the flask is no longer bubbling. After removal of the methylene chloride, place your sample in a 50 mL round bottom flask. Distill the ester by simple distillation (use a heating mantle as the heat source, see Figure bellow, record the boiling point of the ester, and collect it in a clean,
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Study Questions Note: If your TA has not assigned one of the four esters to you, choose one yourself. Write the balanced reaction in the prelab for your assigned or chosen ester only. Calculate theoretical yield as usual, by calculating the limiting reagent, etc. (rather than by the method illustrated in question 3 below). 1) Explain why concentrated H2SO4 is a far superior esterification catalyst compared with concentrated HCl (37% solution in water). 2) Calculate the boiling point of your ester, and the alcohol which was used to synthesize it, in Boulder, Colorado. Assume the barometric pressure is 625 mm. (Boiling points at reduced atmospheric pressure are discussed in the Distillation section of the Handbook.) 3) Assume that the equilibrium constant for esterification of acetic acid with isoamyl alcohol is 3. Calculate the theoretical maximum yield of isoamyl acetate expected using the molar amounts employed in this experiment. Assume that the volume of the reaction mixture remains constant throughout the procedure. *
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Experiment No.12:- Preparation of Benzoic acid
Synthesis of Benzoic Acid by side chain oxidation COOH
KMnO4
Benzoic acid is prepared by oxidation of toluene with an oxygen containing gas, the process is characterized in that the oxidation reaction product is subjected to an extraction with a gas of which the critical temperature is lower than 435 K, this being effected by passing it during at least 1 minute over or through the oxidation reaction product at a flow rate of at least 1 m3 gas per hour per kg of benzoic acid at a temperature of 285-340 K and at a pressure of at least 3 MPa.
Description: The invention relates to a process for the preparation of benzoic acid by oxydation of toluene with gas containing molecular oxygen. This oxidation may take place both in the gas phase and in the liquid phase. In the gas-phase oxidation of toluene to benzoic acid it is preferred to use temperatures of 450700 K. and pressures of 50-2000 kPa. Such a process for the preparation of benzoic acid by gasphase oxidation of toluene is known from the European patent application laid open for public inspection No. 40452. In the liquid phase oxidation of toluene to benzoic acid it is preferred to use temperatures of 390500 K. and pressures of 200-2000 kPa. This liquid phase oxidation may take place in the presence of a solvent, for instance an aliphatic carboxylic acid, in particular acetic acid, and/or in the presence of a halogen-containing substance acting as promotor, but in view of corrosion problems this oxidation by preference takes place in the absence of an aliphatic carboxylic acid and in the absence of a halogen-containing substance acting as promotor. Such a process for the preparation of benzoic acid by liquid phase oxidation of toluene is known from U.S. Pat. No. 4,339,599. A major drawback of these known processes for the preparation of benzoic acid is that the reaction product formed in the oxidation contains a rather large amount of impurities, and with the methods currently known for this it is difficult to separate at least a substantial portion of these impurities from the benzoic acid. One of the impurities that is most difficult to remove is diphenyl oxide (DPO).
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The object of the invention is to provide a process for the preparation of benzoic acid in which said reaction product is in a simple manner purified from said impurities, in particular from diphenyl oxide. The invention therefore relates to a process for the preparation of benzoic acid by oxidation of toluene with gas containing molecular oxygen, which process is characterized in that the oxidation reaction product formed is in a solid or liquid form subjected to an extraction with a gas or gas mixture of which the critical temperature is lower than 435 K., such as SO 2 , N 2 O, NO 2 , NO, CO, CH 4 , N 2 , CO 2 and ethylene and those mixtures, of these gases among themselves and/or with less than 50 vol.-% of other gases, of which the critical temperature is lower than 435 K., preference being given to CO 2 , ethylene or mixtures of these two gases, which extraction is effected by passing this gas or gas mixture over or through the oxidation reaction product during at least 1 minute and by preference at most 500 minutes, and in particular 5-50 minutes, at a flow rate of at least 1 m 3 (NTP) and by preference less than 500 m 3 (NTP), and in particular 5-200 m 3 (NPT), gas per hour per kg benzoic acid at a temperature of 285-340 K. and a pressure of at least 3 MPa and by preference below 300 MPa and in particular 5-100 MPa. The process according to the invention will be elucidated by the following, non-limiting examples. The starting material used in the examples was benzoic acid flakes with a free surface of 2 m 2 per g and with an impurity content, relative to the total weight, of 0.02 wt.-% diphenyl oxide (DPO), 0.02 wt.-% 2-methyldiphenyl (2-MDP) and 0.16 wt.-% of 3-methyldiphenyl and 4methyldiphenyl combined (3- and 4-MDP). Procedure 1- in a round bottom flask place 2ml of Toluene in a 40ml H2O and 2gm KMnO4 2- Boil and Reflux for 30mints. 3- Acidify with concentrated HCl then added it to a beaker, 4- 4gm of Na2SO3 in 20ml water will added to the solution in No.3 until the brown precipitate of MnO2 will dissolve. 5- Cool the mixture till you get a white crystals of Benzoic acid 6- Filter off the product through a Buchner funnel, wash it with water and dry it. 7- Identify the product, find its M.p.
We can also prepare Benzoic Acid from Benzaldehyde In this experiment, you will design and perform an experiment to prepare benzoic acid from benzaldehyde.
You will devise a procedure to perform this experiment and to fully characterize your product. The maximum amount of benzaldehyde you can use is 2.0 g. Prior to doing this part of the experiment, you must compose an experimental protocol in complete detail.
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Experiment No.13:- Preparation of Nitrobenzene Concentrated nitric acid (d. 1-4; 100 c.c. = 140 g.) is poured gradually, with shaking, into a flask capacity about 0-5 1.) containing concentrated sulphuric acid (125 c.c. =230 g.). After the warm mixture has been cooled to room temperature by immersion in coldwater, benzene (90 c.c. = 78 g.; 1 mole) is gradually added with frequent shaking. If, during the addition, the temperature rises above 50°-60° the flask is dipped for a short time in ice-water before further quantities of benzene are added. Each time benzene is added the production of a transient intense brown colour is observed. After the flask has been warmed on the water bath at 60° under an air condenser for half an hour, the lower layer of liquid, which consists of sulphuric and nitric acids, is separated from the upper layer, which contains the nitrobenzene.1 The latter is shaken in a separating funnel, first with water, then with dilute sodium hydroxide solution, and finally again with water. It must be bornein mind that the nitrobenzene now forms the lower layer. After washing and settling, the nitrobenzene is run into a dry flask and warmed with calcium chloride under an air condenser on the water bath until the original milkiness has disappeared. Finally, the substance is purified by distilling (not quite to dryness) from a flask with air condenser. Boiling point 206°-207°. Yield 100-105 g.
The property of yielding nitro-derivatives by the action of nitric acid is a characteristic of aromatic substances. According to the conditions under which, the nitration is carried out one or more nitro-groups can be introduced. Write the equation for the reaction. If an aromatic compound contains saturated aliphatic side chains nitration carried out under the above conditions takes place always in the benzene nucleus and not in the side chain. Since the carbon atoms of benzene are each united directly to only one hydrogen atom, the nitro-derivatives obtained are tertiary and therefore incapable of forming salts, nitrolic acids, or pseudonitroles, as do the primary and secondary nitro-compounds.
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Experiment No.14:- Preparation of Aniline By Reduction of nitrobenzene In the first step of the multi-step sequence, you will reduce nitrobenzene to aniline using chemical reduction: Step 1: Reduction of nitrobenzene
You might ask: why not start this multistep sequence with aniline? One answer is that nitrobenzene is less expensive than aniline, since it is easier to introduce a nitro group to a benzene ring than it is to add an amine group. (Another answer is that we want you to gain practical experience in reduction chemistry techniques.) Nitro compounds can be reduced in one of two general ways: by catalytic hydrogenation using molecular hydrogen or by chemical reduction. Chemical reduction is most often accomplished by treating a mixture of the nitro compound and a metal in the presence of acid. In industry, the metal is usually iron, while in the laboratory setting tin is usually the metal of choice. Since the reaction is done in acidic solution, the amine is obtained as a salt; to obtain the free amine (aniline), it is treated with base. The aniline is isolated from the aqueous reaction mixture by steam distillation. Steam distillation is the distillation of a mixture of water—steam—and an immiscible organic compound. The mixture will boil below 100°C because an immiscible mixture does not behave like an ideal solution (a mixture of miscible liquids). In a mixture of immiscible liquids, the total vapor pressure is the sum of the vapor pressures of the pure individual components. Thus for a steam distillation: P total= P°A+ P°B and the total vapor pressure equals atmospheric pressure and the mixture boils at a lower temperature than the boiling point of either of the components alone. Sinceone of the components is always water, the mixture will always boil below 100°C. After the steam distillation, you will have a mixture of water and aniline. These
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compounds are immiscible, so you could separate the aniline layer from the water layer in the steam-distillate. In this reaction scheme, separation is not necessary because the next step is performed in aqueous solution.
Procedure Section: Reduction of nitrobenzene: Place 30 mmoles of nitrobenzene and 65 mmoles of mossy tin in a 250 mL round bottom flask, securely clamped above a stir motor. Place a Claisen adaptor on top of the flask; put a water-cooled condenser on one outlet of the Claisen and a separatory funnel on the other. Add a spin bar to the flask and turn on the stir motor. Place 15 mL of concentrated HCl in the separatory funnel. Add the HCl to the nitrobenzene/tin mixture a few mLs at a time. After each addition, monitor the flask so that it does not get too hot; if necessary, immerse the reaction flask briefly in a cold water bath. After the initial reaction has subsided, add another portion of the acid. Again, control the temperature of the reaction in a cold water bath. Continue until all of the HCl has been added. After all of the acid has been added let the mixture stir at room temperature for about 10 min. Remove the separatory funnel (and rinse it) and place a ground glass stopper on the open Claisen outlet (the other outlet still has the water-cooled condenser). Place a heating mantle under the reaction mixture and heat (Variac setting 35) and stir for 20 min. Test to see if the reaction has gone to completion by testing for unreacted nitrobenzene (below). If nitrobenzene remains, heat and stir for an additional 10 min and testagain. Test for unreacted nitrobenzene: Put a few drops of the reaction mixture in a small amount of water in a test tube; a clear solution (no oily drops) indicates that there is no nitrobenzene present. When the reaction is complete, cool the reaction flask to room temperature. While stirring, carefully add 18 mL of 50% NaOH through the Claisen adaptor. This reaction is exothermic, so have a cool water bath (not an ice bath) ready in case the flask gets too warm. The mixture must be strongly alkaline to ensure complete liberation of the aniline. Dilute the reaction mixture with 40 mL of water and then steam distill the mixture using a heating mantle as the heat source (Variac setting 100). Collect the distillate in a 100 mL graduated cylinder: the first 18 mL or so of distillate should be quite cloudy because you are distilling over a mixture of aniline and water. Once the distillate ceases to be turbid, collect an additional 4 mL. Transfer the entire volume of distillate to an Erlenmeyer (do not stopper the flask until the solution is cool!) and save for use in the acetylation step. Place the pot residue in the Aqueous Waste carboy in the main hood.
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Experiment No.15:- Preparation of Acetanilide Aniline is acetylated with acetic anhydride to produce acetanilide: Step 2:Preparation of acetanilide.
Note that the desired final product in this experiment is a mono-nitroaniline. Why, then, is this step of acetylating the aniline included in the reaction scheme? The reason is that direct nitration of aniline to obtain a mononitro derivative is essentially impossible due to the high reactivity of nitric acid* toward aniline in electrophilic aromatic substitutions. Also, aniline is oxidized by nitric acid. In order to successfully nitrate aniline to a mononitro derivative, it is first converted to acetanilide.
Procedure Section: Preparation of acetanilide: Dilute the distillate from the previous step with water to a final volume of 65 mL. Add a spin bar and place it over a stir motor. Add 2.5 mL of concentrated hydrochloric acid and stir to obtain a homogeneous solution. Dissolve 4.5 g of sodium acetate trihydrate in 10 mL of water in a beaker. Measure 3.5 mL of acetic anhydride into a graduated cylinder. Warm the solution of aniline/ hydrochloric acid to 50°C on a steam bath, add the acetic anhydride, stir, then add the sodium acetate solution all at once with stirring . Remove the heat source; a white solid should begin to precipitate. Continue to stir the mixture for 20 min then cool it in an ice bath to complete crystallization. Isolate the product by suction filtration, wash it with cold water, and allow it to dry. It is imperative that your acetanilide be dry for the next step. You can dry it by leaving it in an open container in your lab drawer until the next lab period. If you plan to do Step 3 immediately, you should pull air through the sample in the Büchner funnel for at least 30 min. Determine the melting point and the yield of dry acetanilide. * If aniline and nitric acid are mixed directly, a violent oxidat ion of the aniline occurs which can cause the mixture to ignite.
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Experiment No. 16 :- Preparation of p-bromo Acetanalide NHCOCH3
NHCOCH3
1-Br2 2-H3O+
Br
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Experiment No.17 :- Diazonium salt Reactions & preparation of methyl orange
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Methyl Orange Preparation
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Mechanism of Methyl Orange Preparation
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Experiment No.18 :- Properties of Aldehyde & ketones
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Experiment No.19 :- Preparation of Acetophenone-oxime
References: (POC by FREDERICK GEORGE MANN 1978)
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Experiment No.20 :- Preparation f Phenyl Hydrazones
Phenylhydrazine condenses readily with aldehydes and ketones to give phenylhydrazones, which, being usually crystalline compounds of sharp C6H5CHO -f H2NNHC6H5 ----> C6H5CHiNNHC6H5 -f H2O Benzaldehyde Phenylhydrazine Benzaldehyde Phenylhydrazone melting-point, can therefore be used to identify the aldehydes and ketones from which they have been formed. For this purpose phenylhydrazones are frequently more suitable than oximes (p. 93) since their greater molecular weight causes a lower solubility in most solvents, and they can therefore often be more easily isolated and recrystallised. The phenylhydrazones of the lower aliphatic aldehydes and ketones, however, often have low melting-points, and are thus not suitable for identification purposes: to overcome this difficulty, substituted phenylhydrazines such as />nitrophenylhydrazine, (NO2C6H4NHNH2),2,4-dinitrophenylhydrazine (pp. 263, 346), nd p-bromophenylhydrazine are often used, since the corresponding substituted phenylhydrazones usually crystallise well, and are of low solubility and high meltingpoint. Phenylhydrazine is usually dissolved in acetic acid for hydrazone formation: if a salt of phenylhydrazine with an inorganic acid is used, it must be mixed with an excess of sodium acetate (see preparation of osazones, p. 137). Required: Acetic acid, 0-3 ml.; phenylhydrazine, 0*4 ml.; benzaldehyde, 0-2 ml. Dissolve 03 ml. of glacial acetic acid in 2 ml. of water in a 25 ml. conical flask, and add 0-4 ml. (0-44 g.) of phenylhydrazine. Mix thoroughly to obtain a clear solution of phenylhydrazine acetate and then add 0-2 ml. (021 g.) of benzaldehyde. Cork the flask securely and shake the contents vigorously. A yellow crystalline mass of the hydrazone soon begins to separate. Allow to stand for 15 minutes, with occasional shaking, and then filter the solid product at the pump, wash first with very dilute acetic acid and then with water, and finally drain thoroughly. Recrystallise the material from rectified or methylated spirit, the benzaldehyde phenylhydrazone being thus obtained in fine colourless needles, m.p. 157°: yield, 0-4 g.(POC by FREDERICK GEORGE MANN 1978) 62
Experiment No.21 :- Principles of Extraction Extraction Of oil from sunflower seeds
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Experiment No.21:- Extraction of Caffeine from tea leaves Caffeine forms white hexagonal crystals by sublimation. Caffeine has a melting point of 238 Celsius, but the crystals begin to sublime when heated to 178 Celsius. Caffeine is only moderately soluble in water, but more soluble in hot water. The crystals are also moderately soluble in alcohol, acetone, but are much more soluble in methylene chloride, chloroform, and practically insoluble in ether. Caffeine is capable of forming a hydrate, which looses it water of hydration when heated to 80 Celsius. Caffeine is a widely used stimulant, ingested by millions in the form of coffee, tea, ect.,
Method 1: Extraction of caffeine from tea leaves Hazards: Use proper ventilation when using toluene and hexane, and avoid inhalation of the fumes.
Procedure: Into a suitable beaker or flask, place 825 milliliters (28 fluid oz.) of water, and then add and dissolve 60 grams (2.1 oz.) of sodium carbonate. Thereafter, boil the mixture, and once the water begins to boil, add in 30 to 40 tea bags (any brand of tea can be used). Thereafter, boil the mixture and allow the tea bags to soak for 15 minutes in the usual manner. After 15 minutes, remove the heat source, and allow the tea mixture to cool to about 50 Celsius. Thereafter, remove the tea bags, and then allow the tea mixture to cool to room temperature. Thereafter, add in 90 milliliters (3 fluid oz.) of methylene chloride, and then stir the mixture gently for about 30 to 40 minutes. Note: do not shake the mixture vigorously as an emulsion will form. After stirring the mixture for about 30 to 40 minutes, gently pour the mixture into a seperatory funnel, and then remove the lower organic solvent layer. Thereafter, place this lower organic layer aside temporarily, and then repeat the extraction process with four 90milliliter portions (four 3 fluid oz. portions) of methylene chloride upon the upper water layer. After extracting the upper water layer four more times, combine all lower methylene chloride portions, if not already done so, and then dry the combined methylene chloride portions by adding in 15 grams (0.52 oz.) of anhydrous sodium sulfate. Then stir the mixture briefly, and then filter-off the sodium sulfate. Now, place the dried methylene chloride portion into a distillation apparatus, and distill-off the methylene chloride until a dry residue remains. When this point is achieved, remove the heat source, and then collect the dry residue. Finally, re-crystallize this dry residue from a toluene/hexane solvent mixture prepared by adding and dissolving 21 milliliters (0.71 fluid oz.) of toluene to 30 milliliters (1 fluid oz.) of hexane, and after the re-crystallization process, vacuum dry or air dry the collected caffeine crystals. These crystals can be sublimed using a standard sublimation setup (see iodine) to afford highly pure crystals of 99% purity.
References: KINGS CHEMISTRY SURVIVAL GUIDE by Jared B. Ledgard 2003 65
Experiment No.22:- Principles of Chromatography
Thin-Layer Chromatography The Separation of Analgesics Analgesics are substances that relieve pain. The most common of these is aspirin, a component of more than 100 nonprescription drugs. Aspirin is among the most fascinating and versatile drug known to medicine and it is among the oldest— the first known use of an aspirin-like preparation can he traced to ancient Greece and Rome. Salicigel, an extract of willow and poplar hark, has been used as a pain reliever analgesic) for centuries. In the middle of the last century it was found that salicigen is a glycoside formed from a molecule of salicylic acid and a sugar molecule. Salicylic acid is easily synthesized on a large scale by heating sodium phenoxide with carbon dioxide at 150°C under slight pressure (the Kolbe synthesis). Unfortunately, however, salicylic acid attacks the mucous membranes of the mouth and esophagus and causes gastric pain that may he worse than the discomfort it was meant to cure. Felix Hoffmann, a chemist for Friedrich Bayer, a German dye company, reasoned that the corrosive nature of salicylic acid could he altered by addition of an acetyl group; and in 1893 the Bayer Company obtained a patent on acetylsalicylic acid, despite the fact that it had been synthesized some 40 years previously by Charles Gerhardt. Bayer coined the name Aspirin for its new product to reflect its acetyl nature and its natural occurrence in the Spiraea plant. Over the years they have allowed the term aspirin to fall into the public domain so it is no longer capitalized. The manufacturers of Coke and Sanka work hard to prevent a similar fate befalling their trademarks. In 1904 the head of Bayer, Carl Duisberg, decided to emulate John D. Rockefeller's Standard Oil Company and formed an "interesscn gemeinschaft" (I.G.) of the dye industry (Farbenindustrie). This cartel completely dominated the world dye industry before World War I, and it continued to prosper between the wars, even though some of its assets were seized and sold after World War I. After World War I an American company, Sterling Drug, bought the rights to aspirin for $5.3 million. Sterling was bought by Eastman Kodak in 1988, then sold to SmithKline Beacham. Because of their involvement at Auschwitz, the top management of I.G. Farbenindustrie was tried and convicted at the Nuremberg trials after World War II, and the cartel broken into three large branches—Bayer, Hoechst, and BASF (Badische Anilin and Sodafabrik)—each of which does more business than DuPont, the largest American chemical company. In 1997 the American rights to the Bayer name and trademark were sold back to Bayer A.G. for $1 billion. By law, all drugs sold in the United States must meet purity standards set by the U.S. Food and Drug Administration (FDA), and so all aspirin is essentially the same. Each fivegrain tablet contains 0.325 g of acetylsalicylic acid held together with a binder. The remarkable difference in price for aspirin is primarily a reflection of the advertising budget of the company that sells it. Bayer has 5% of the painkiller market; lower-priced generic aspirin has 18%. Aspirin is an analgesic (painkiller), an antipyretic (fever reducer), and an antiinflammatory agent. It is the premier drug for reducing fever, a role for which it is uniquely suited. As an anti-inflammatory, it has become the most widely effective treatment for arthritis. Patients suffering from arthritis must take so much aspirin (several grams per day) 66
that gastric problems may result. For this reason aspirin is often combined with a buffering agent. Bufferin is an example of such a preparation. The ability of aspirin to diminish inflammation is apparently due to its inhibition of the synthesis of prostaglandins, a group of C-20 molecules that enhance inflammation. Aspirin alters the oxygenase activity of prostaglandin synthetase by moving the acetyl group to a terminal amine group of the enzyme. If aspirin were a new invention, the FDA would place many hurdles in the path of its approval. It has been implicated, for example, in Reye's syndrome, a brain disorder that strikes children and young people under 18 who take aspirin after flu or chicken pox. It has an effect on platelets, which play a vital role in blood clotting. In newborn babies and their mothers, aspirin can lead to uncontrolled bleeding and problems of circulation for the baby— even brain hemorrhage in extreme cases. This same effect can be turned into an advantage, how-ever. Heart specialists urge potential stroke victims to take aspirin regularly to inhibit clotting in their arteries, and it has been shown that one-half tablet per day will help prevent heart attacks in healthy men. Aspirin is found in more than 100 common medications, including Alka-Seltzer, Anacin, Coricidin, Excedrin, Midol, and Vanquish. Despite its side effects, aspirin is one of the safest, cheapest, and most effective nonprescription drugs, although acetaminophen (Tylenol, etc.) has 40% and ibuprofen (Advil, etc.) has 26% of the painkiller market in dollar volume ($2.47 billion in 1996). Naproxen (Aleve) has 6% of the market. Aspirin is made commercially employing the same synthesis used here. In the this experiment, analgesic tablets will be analyzed by thin-layer chromatography to determine which analgesics they contain and whether they contain caffeine, which is often added to counteract the sedative effects of the analgesic. In addition to aspirin and caffeine, the most common components of analgesics are, at present, acetaminophen and ibuprofen (Motrin). In addition to one or more of these substances, each tablet contains a hinder, often starch, micro-crystalline cellulose, or silica gel. And to counteract the acidic properties of aspirin, an inorganic buffering agent is added to some analgesics. Inspection of labels will reveal that most cold remedies and decongestants contain both aspirin and caffeine in addition to the primary ingredient. To identify an unknown by TLC, the usual strategy is to run chromatograms of known substances (the standards) and the unknown at the same time. If the unknown has one or more spots that correspond to spots with the same R / values as proprietary drugs that contain one or more of the common analgesics and sometimes caffeine are sold under the names of Bayer Aspirin, Anacin, Datril, Advil, Excedrin, Extra Strength excedrin, Tylenol, and Vanquish. Note that ibuprofen has a chiral carbon atom. One enantiomer is more effective than the other.
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Procedure Using scissors cut two or three pieces of the pre-prepared silica-gel TLC plates into a size that will fit easily into the developing chambers. Be careful not to touch the surface of the plates as your fingerprints will show up later when the plates are developed. Following the procedures outlined in your lab text on pages 104-111, draw a light pencil line about 1 cm from the end of a chromatographic plate, and on this line spot aspirin, acetaminophen, ibuprofen, and caffeine, which are available as reference standards. Use a separate capillary for each standard. Make each spot as small as possible, preferably less than 0.5 mm in diameter. You may use the blower to facilitate the evaporation of the solvent between applications. Examine the plate under the ultraviolet (UV) light to see that enough of each compound has been applied; if not, add more. On a separate plate run three of the unknowns and one of the aspirin standard. The unknown sample is prepared by crushing a part of a tablet, adding this powder to a test tube or small vial along with an appropriate amount of ethanol, and then mixing the suspension. Not all of the tablet will dissolve, but enough will go into solution to spot the plate. The binder—starch or silica—will not dissolve. The 1% solutions should have been prepared by the lab manager and are ready to use. Use as the solvent for the chromatogram a mixture of 95% ethyl acetate and 5% acetic acid , or the instructor may supply a different solvent. After the solvent has risen to about 2/3 of the length of the plate, remove the plate from the developing chamber. Quickly mark the solvent front with a pencil and allow the solvent to dry. Examine the plate under UV light to see the components as dark spots against a bright green-blue background. Outline the spots with a pencil. The spots can also be visualized by putting the plate in an iodine chamber made by placing a few crystals of iodine in the bottom of a capped 4-oz jar. Calculate the R f. values for the spots, and identify the components in the unknown. C l e a n i n g U p : Solvents should be placed in the organic solvents container; and dry, used chromatographic plates and scraps can be discarded in the non-hazardous solid waste container. Don’t discard your plates until you have copied them! R e p o r t a s i n t h e E n d o f t h i s m a n u a l : Turn the data sheet along with a photocopy of your TLC plates with the work for the R f calculation done on the copy (No copies of the work!).
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Experiment No.23:- Separation of Amino acid by paper Chromatography
A Description Thin layer chromatography (TLC) is a method for identifying substances and testing the purity of compounds. TLC is a useful technique because it is relatively quick and requires small quantities of material. .
Separations in TLC involve distributing a mixture of two or more substances between a stationary phase and a mobile phase. The stationary phase is a thin layer of adsorbent (usually silica gel or alumina) coated on a plate. The mobile phase is a developing liquid which travels up the stationary phase, carrying the samples with it. Components of the samples will separate on the stationary phase according to how much they adsorb on the stationary phase versus how much they dissolve in the mobile phase. Equipment used in a thin layer chromatography experiment
Commercial TLC plate after development in normal lighting
Same TLC plate held under a UV lampNote the appearance of additional spots.
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(Note: Rf values often depend on the temperature and the solvent used in the TLC experiment; the most effective way to identify a compound is to spot known substances next to unknown substances on the same plate.) In addition, the purity of a sample may be estimated from the chromatogram. An impure sample will often develop as two or more spots, while a pure sample will show only one spot.
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Organic Laboratory Data Sheet Name ____________________________________ Partner _________________________ Experiment Name: I.
II.
Reaction equation(s) using structures and names:
Theoretical yield (recovery) and literature melting/boiling point: Theoretical Yield:
Literature BP/MP:
III. Data: Mass of purified product obtained: Discuss a useful test:
Melting Points Crude product: Purified product: (Literature value):
% Yield after purification:
V.
Use of this Compounds
VI. IR Spectrum and TLC analysis (Attach labeled spectrum and copy of TLC plate to report): Discuss your results here and find in books IR and NMR data:
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References 1- Organic Chemistry by Francis Carey,2005. 2- Vogel's , Text book of Practical Organic chemistry ,by Brian S.Furniss and Antony J.Hannaford, Fifth edition 1989. 3- Webpage of Wikipedia for most of experiments'. the free encyclopedia.htm4- Practical organic chemistry by FREDERICK GEORGE MANN 1960. 5- Laboratory methods of Organic chemistry by L.GatterMann, New York 1937. 6- Advance Practical organic chemistryby J.Leonard, second edition,1998.
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كيمياي ئؤرطانيكي ثراكتيكي بؤ ثؤلي دووهةمى بةشي كيميا لةاليةن د.بارام أمحد جاف دكتؤرا لة كيمياي ئؤرطانيك 5002 لةزانكؤى لويس ثاستؤر زانكؤى سليَمانى 5002 73
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كيمياي ئؤرطانيكي ثراكتيكي بؤ ثؤلي دووهةمى بةشي كيميا لةاليةن د.بارام أمحد جاف دكتؤرا لة كيمياي ئؤرطانيك 5002 لةزانكؤى لويس ثاستؤر زانكؤى سليَمانى 5002 74
5000
