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Laboratory manual

Organic Chemistry 2

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Content:

Experiment 1:Experiment 1: identifying an Unknown compound by solubility,

functional group Tests and spectral Analysis…………………..........……………3.

Experiment 2:: PART B (WEEK 2) - CLASSIFICATION TESTS… …..........….7

Experiment 3:esterification…………………………………….........…….....…….11

Experiment 4:Nitration of Aromatic compounds…………….....................……….19

Experiment 5: Synthesis of Aspirin……………………....…………………………23

Experiment 6: Synthesis of Hexahydro-1,3,5-tri-p-tolyl-s-triazine………….....…..26

Experiment 7: Synthesis of glucosazone…………...……………………………….27

Experimental 8: Synthesis of triphenylmethanol from benzophenone via Grignard

reagent……………………………………………………………………………….28

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Experiment 1: identifying an Unknown compound by solubility, functional group Tests and spectral Analysis.

Introduction The identification and characterization of the structures of unknown substances are an important part of organic chemistry. Although it is often possible to establish the structure of a compound on the basis of spectra alone (IR, NMR, etc.), the spectra typically must be supplemented with other information about the compound: physical state and properties (melting point, boiling point, solubility, odor, color, etc.), elemental analysis, and confirmatory tests for functional groups. In this experiment you will carry out several qualitative tests that will allow you to identify functional groups in organic molecules. You will then apply what you have learned by characterizing unknown organic compounds in terms of their functional group and solubility behavior. The functional groups you will examine include amines, alcohols, carboxylic acids, alkenes, alkanes, and alkyl halides. PART A (WEEK 1) - SOLUBILITY TESTS Organic compounds follow three interdependent rules of solubility: 1. small organic molecules are more soluble in water than are large organic molecules; 2. polar organic molecules, especially those capable of hydrogen bonding, are more soluble in waterthan are nonpolar molecules; and 3. compounds in their ionic forms are more soluble in water than their neutral forms. For example, benzoic acid is not soluble in water, yet it is soluble in sodium hydroxide solutionand in sodium hydrogen carbonate solution because these bases react with benzoic acid to form thewater-soluble benzoate ion. The solubility of carboxylic acids and amines is so characteristic thatsolubility tests alone differentiate these functional groups from all the others in this experiment. The solubility flowchart shown in Figure 2 provides the scheme for this experiment. The first testto perform on all unknowns is water solubility. Figure 2. Solubility Test Flow Chart.

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Water Small, polar organic compounds such as alcohols, aldehydes, ketones, amines, carboxylic acids, and afew phenols are soluble in water. Water-soluble compounds are tested with pH paper to see if they areacidic or basic. A pH of 4 or lower indicates a carboxylic acid. A pH of 8 or higher indicates an amine.Water-soluble compounds are tested with 5% sodium hydrogen carbonate (NaHCO3) to determine whether or not they are carboxylic acids. Carboxylic acids react with NaHCO3 to producecarbon dioxide bubbles, as shown below in Equation 3. Large alcohols, aldehydes, ketones, amines, carboxylic acids, and phenols are not soluble in water. Alkanes, alkyl halides, and alkenes are not soluble in water, regardless of their size. These water insoluble compounds are tested for their solubility in the following reagents. 5% Sodium Hydroxide Water-insoluble compounds are first tested with 5% sodium hydroxide (NaOH). Sodium hydroxide is a strong base that ionizes strong or weak (Figure 2 Solubility flowchart) acids. Thus, both carboxylic acids and phenols are converted to salts and dissolve in aqueous solution. Non-acidic compounds will not dissolve. The reactions of carboxylic acids and phenols are shown in Equations 1 and 2, respectively.

5% Sodium Hydrogen Carbonate Water-insoluble compounds that are soluble in 5% NaOH are then tested with 5% sodium hydrogen carbonate (NaHCO3). Strongly acidic compounds such as carboxylic acids react with NaHCO3 to form water-soluble salts, as shown in Equation 3. The reaction also produces bubbles of carbon dioxide (CO2). This test is commonly misinterpreted because CO2 bubbles are tiny. Careful observation is essential. Phenols are less acidic than carboxylic acids and do not react with NaHCO3 to form water-soluble salts. As a result, phenols are insoluble in 5% NaCHO3.

5% Hydrochloric Acid Water-insoluble compounds that are insoluble in 5% NaOH are tested with 5% hydrochloric acid (HCl). If a compound is soluble in 5% HCl, it is an amine. Amines are organic bases that react with HCl to form water-soluble amine salts, as shown in Equation 4.

Concentrated Sulfuric Acid Water-insoluble compounds that are insoluble in 5% HCl are tested with concentrated sulfuric acid(H2SO4). Virtually all organic compounds containing alkene functional groups or oxygen

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or nitrogen atoms are soluble in concentrated H2SO4. These functional groups typically react with H2SO4 to form new compounds. Only alkanes, alkyl halides, and some aromatic compounds are insoluble in H2SO4. Table 1 Known Positive And Known Negative Test Compounds For Solubility Tests

PROCEDURE PART A (WEEK 1) Preview: Perform the water solubility test on the known positive, known negative, and unknown Perform subsequent solubility tests If the solubility tests point to a carboxylic acid or amine, the classification is complete If the solubility tests suggest any other functional groups, you will preform classification

tests during week 2 appropriate to those groups until the unknown is narrowed to only one functional group Equipment: Microspatula glass stirring rod 10-mL graduated cylinder 6-10 test tubes, 15 x 125-mm 6-10 test tubes, 10 x 75-mm test tube rack pH paper 1.0-mL transfer pipet Pasteur pipet, with latex bulb Solubility Tests: Perform all tests in duplicate using an unknown, a known positive, and a known negative. Mix well to make certain that liquid samples are not floating in the meniscus. Allow several minutes for compounds to dissolve. Be patient and observe closely. Conduct the solubility tests following the pattern shown in Figure 1 above. Verify your solubility test results with your laboratory instructor before performing the classifications tests in Part 2. Use cleantest tubes for each test. 1. Performing the Water Solubility Test Add 1 drops of a liquid sample or about 25 mg of a solid sample to 0.5 mL of distilled or deionized water in a test tube. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Record the sample as soluble or insoluble. If the unknown is water-soluble, test the solution with pH paper. Also test the pH of water as a control. A solution at pH 4 of lower suggests a carboxylic acid. A solution at pH 8 or higher suggests an amine. 2. Performing the 5% Sodium Hydroxide Solubility Test If your compound is water-soluble, proceed to Part 3. For water-insoluble compounds, add 1 drops of a liquid sample or about 25 mg of a solid sample to 0.5mL of 5% NaOH in a test tube. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Record the sample as soluble or insoluble.

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To verify that a compound has dissolved, add 5% HCl to the NaOH mixture until the solution is acidic to pH paper. Look for a precipitate, indicating that the water-soluble salt has converted back into the water-insoluble compound. Solubility in NaOH indicates either the carboxylic acid or phenol . 3. Performing the 5% Sodium Hydrogen Carbonate Solubility Test a. For Water-Soluble Compounds Put 1 drops of liquid sample or about 25 mg of solid sample in a dry test tube. Add 0.5 mL of 5% sodium hydrogen carbonate (NaHCO3). Do not stir. Watch for bubbles at the interface of the phases. Then tap the tube with your finger to mix or stir gently with a glass stirring rod. Record the sample as soluble or insoluble. Generation of bubbles and solubility indicates a carboxylic acid. Solubility without generation of bubbles indicates a low molar mass alcohol, aldehyde, ketone, or amine. Conduct classification tests todetermine which functional group is present. If no bubbles were observed, put 1 drop of liquid sample or about 25 mg of solid sample in a dry test tube. Using a fume hood, add about 0.5 mL of ether. Then immediately add 0.5 mL of 5% NaHCO3. Observe whether or not bubbles are generated at the ether-water interface. Generation of bubbles indicate a carboxylic acid. b. For Water-Insoluble Compounds Put 1 drop of liquid sample or about 25 mg of solid sample in a dry test tube. Add 0.5 mL of 5% sodium hydrogen carbonate (NaHCO3). Do not stir. Watch for bubbles at the interface of the phases. Then tap the tube with your finger to mix or stir gently with a glass stirring rod. Record the sample as soluble or insoluble. Generation of bubbles or solubility indicates a carboxylic acid. If the compound is not soluble in NaHCO3 but is soluble in NaOH, it is likely a phenol. Confirm the presence of phenol with a phenol classification test. 4. Performing the 5% Hydrochloric Acid Solubility Test For compounds insoluble in water and insoluble in 5% NaOH, add 1 drop of a liquid sample or about 25 mg of a solid sample to 0.5 mL of 5% HCl in a test tube. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Record the sample as soluble or insoluble. If the compound is soluble in 5% HCl, it is most likely an amine. 5. Performing Concentrated Sulfuric Acid Solubility Test If the compound is insoluble in 5% HCl and 5% NaOH, add 1 drop of a liquid sample or about 25 mg of a solid sample to 0.5 mL of concentrated sulfuric acid (H2SO4) in a dry test tube. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Do not use a metal spatula. Record the sample as soluble or insoluble. Interpret a color change or a precipitate as soluble. If the compound is soluble in H2SO4, the sample is an alkene, an alcohol, an aldehyde, or a ketone. Conduct classification tests for each compound type. If the compound is insoluble in H2SO4, the sample is an alkane or an alkyl halide. Conduct classification tests for alkyl halides. If alkyl halide tests are negative, the compound is an alkane. Based upon the positive and negative results from the above experiments you should now be able to narrow the possibilities for the functional group(s) present in your unknown sample. You should now carefully decide which experiments are needed during Part B (Week 2) to distinguish those possibilities.

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Experiment 2: PART B (WEEK 2) - CLASSIFICATION TESTS Bromine in Cyclohexane Alkenes react with bromine (Br2) in cyclohexane, an orange solution, to produce colorless vicinal dibromides, as shown in Equation 5. This test is commonly used for water-insoluble compounds. Alkenes with strong electron-withdrawing groups may fail to react. Phenols, phenyl ethers, and some aldehydes and ketones also react to decolorize bromine in cyclohexane.

Potassium Permanganate Alkenes are oxidized to diols by dilute potassium permanganate (KMnO4), as shown in Equation 6. The purple color of KMnO4 disappears and is replaced by the brown color of manganese dioxide (MnO2). Because KMnO4 is a strong oxidizing agent, aldehydes, some primary and secondary alcohols, phenols,mand aromatic amines can also react.

Silver Nitrate in Ethanol Alkyl halides react with silver nitrate (AgNO3) in ethanol by the SN1 mechanism. Tertiary, allylic, and benzylic halides give an immediate precipitate at room temperature, as shown in Equation 7. Secondary halides require several minutes to give a precipitate, primary halides require hours.

Iron(III) Chloride Many phenols react with iron(III) chloride (FeCl3) solution to give brightly colored complexes. Many of these complexes are short-lived; the color may fade soon after it forms. Some phenols may not react at all, so a negative iron(III) chloride test is inconclusive. Aldehydes or ketones with significant enolic character can also give colored complexes with FeCl3. 2,4-Dinitrophenylhydrazine Aldehydes and ketones rapidly form yellow, orange, or red precipitates with 2,4-dinitrophenylhydrazine (DNP) reagent, as shown in Equation 11.

Schiff Test In a complex series of reactions that is not completely understood, Schiff reagent reacts only withaldehydes to produce a purple fuchia solution. A faint pink color results from the initial

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reaction and doesnot constitute a positive test. The Schiff test is the most sensitive rest for aldehydes. However, the Schiff test is subject to giving false positives and false negatives.

Equipment 250-mL beaker microspatula glass stirring rod 6-10 test tubes, 15 x 125-mm 10-mL graduated cylinder 6-10 test tubes, 10 x 75-mm hot plate test tube rack pH paper thermometer, -10 to 260°C 1.0-mL transfer pipet tongs Pasteur pipet, with latex bulb. Procedure Week 2. Performing the Bromine in Cyclohexane Test for Alkenes Place 1 mL of cyclohexane in a small test tube. Add 3 drops of Br2/H2O. Mix until the bromine color appears in the top cyclohexane layer. For liquid samples, add 2 drops of sample to the Br2/H2O. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record whether or not the orange color disappears. For solid samples, place 30 mg of solid into a test tube. Add 5 drops of acetone. Add the acetone solution to the Br2/H2O. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record whether or not the orange color disappears. If the orange color disappears quickly, the sample may be an alkene. NOTE: Phenols, phenyl ethers, and some aldehydes and ketones may test positive. Performing the Potassium Permanganate Test for Alkenes If your sample is water-soluble, place 1-2 mL of water into a small test tube. If your sample is waterinsoluble, place 1-2 mL of 95% ethanol into a small test tube. Add 2 drops of a liquid sample or about 30 mg of a solid sample. Add 2 drops of 1% KMnO4. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Let the mixture stand 10-20 s. Note and record whether or not the purple color disappears. If the purple color disappears and a brown color or precipitate appears, the compound may be an alkene. Note: The brown color or precipitate may not appear. Aldehydes, some primary and secondary alcohols, phenols, and aromatic amines may test positive.

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Performing the Silver Nitrate in Ethanol Test for 2° and 3° Alkyl Halides Place 1 mL of 2% AgNO3 in ethanol into a small test tube. For liquid samples, add 2 drops of sample to the 2% AgNO3. Tap the tube with your finger to mix or stir gently with a glass stirring rod. For solid samples, place 30 mg of solid into a test tube. Add 5 drops of ethanol. Add this ethanol solution to the 2% AgNO3 in ethanol. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record whether or not a precipitate forms. An immediate precipitate indicates a tertiary, allylic, or benzylic halide. Performing the Sodium Iodide in Acetone Test for 1° and 2° Alkyl Halides Place exactly 1.0 mL of NaI in acetone into a small test tube. Add 3 drops of a liquid sample. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Allow the tube to stand 3-6 min at room temperature. Note and record whether or not a precipitate forms. A white precipitate indicates a primary, allylic, or benzylic halide. Performing the TCICA Test for Alcohols Place 0.5 mL of the TCICA test solution into a small test tube. Add 1 drop of 5% HCl. Tap the tube with your finger to mix or stir gently with a glass stirring rod. For liquid samples, add 1 drop of the sample. Tap the tube with your finger to mix or stir gently with a glass stirring rod. For solid samples, dissolve about 20 mg of solid in 1-2 drops of acetonitrile. Add this solution to the TCICA/HCl solution. Note and record whether or not a precipitate forms. The formation of a precipitate within one min indicates a secondary alcohol; the formation of a precipitate between 3-20 min indicates a primary alcohol. Performing the Iron(III) Chloride Test for Phenols Place 1 mL of 95% ethanol into a small test tube. Add 2 drops of a liquid sample or about 30 mg of a solid. Add 3-5 drops of 3% FeCl3. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record any formation of a brightly colored solution. The presence of bright color, even briefly, indicates a phenol. NOTE: Some aldehydes or ketones also give colored complexes with FeCl3. Performing the Bromine in Water Test for Phenols Place 1 mL of 95% ethanol into a small test tube. Add 5 drops of a liquid sample or about 30 mg of a solid. Add a drop of water. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Add 1 drop of Br2/H2O. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record whether or not the orange color disappears. The disappearance of the orange color indicates a phenol. Performing the 2,4-DNP Test for Aldehydes and Ketones For liquid samples, place 1 drop of sample into a clean, dry test tube. Add up to 20 drops of 2,4-DNP solution. Tap the tube with your finger to mix or stir gently with a glass stirring rod. For solid samples, add about 30 mg of solid into a clean, dry test tube. Add 0.5 mL of ethanol. Tap the tube with your finger to mix or stir gently with a glass stirring rod. If the unknown does not dissolve, prepare a warm-water bath by placing 175-200 mL of tap water into a 250-mL beaker. Use a hot plate to heat the water to 40°C. Place the test tube into a warm-water bath and swirl the tube until the unknown is dissolved. Cool the solution to room temperature. Add up to 20 drops of 2,4-DNP solution. Tap the tube with your finger to mix or stir gently with a glass stirring rod. Note and record whether or not a precipitate forms. An immediate, brightly colored precipitate indicates an aldehyde or ketone. Preforming the Schiff Test for Aldehydes. Add 1 drop of a liquid sample or about 15 mg of a solid sample a clean, dry test tube. Place 2 mL of Schiff solution in a test tube. Mix well. After 5 min, mote the color of the solution and record your observation.

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A fuchsia color indicates an aldehyde. Cleaning Up And Getting the Spectra Once you believe you have identified the functional groups present in your unknown, check with your TA to see if you have determined them correctly. After your TA has confirmed your assignment, you should clean-up your work area and rinse any remaining unknown compound into the organic waste using acetone. DO NOT PUT YOUR UNKNOWN INTO THE WASTE UNTIL YOU HAVE CLEARED IT WITH YOUR TA. If you have misassigned your functional groups and disposed of your unknown, you will be penialized to obtain an additional sample. Thoroughly rise the vials you unknowns came in, and them present them to your TA for inspection. Once your TA is satisfied that you have cleaned-up properly, they will give you the spectra so you can complete Part 3 of the lab. Wash your hands with soap or detergent before leaving the laboratory. Part C. Using Spectra To Identify Your Unknown Compound. In Parts A and B, you used solubility and chemical reactivity test to identify the functional group(s) contained within your unknown compound. Using these results in conjunction with molecular formula and the spectra data that you have received, please fully identify the unknown compound. Assign the 1H and 13C NMR spectra completely. In your lab report, please state the identity of each of your unknown compounds along with the unknown number. Discuss the relevance of the solubility and chemical tests to this structural assignment. Pre-Laboratory Assignment 1. What risks do you run by not performing the qualitative tests in duplicate? 2. (a) Why is it important to have clean test tubes before running a test? (b) Before which tests should acetone not be used to clean the test tubes? 3. Why is water solubility the first test to run? 4. Why run solubility tests before running the functional group classification tests? 5. Determine the functional group present in these unknown: (a) Unknown A is soluble in water and gives bubbles with5% NaHCO3. (b) Unknown B is insoluble in water, insoluble in 5% NaOH, but soluble in 5% HCl. (c) Unknown C is insoluble in water, insoluble in 5% NaOH, insoluble in 5% HCl, soluble with a color change in conc. H2SO4, and decolorizes both KMnO4 (aq) and bromine in cyclohexane. (d) Unknown D is soluble in water, does not produce bubbles with 5% NaHCO3, gives a precipitate with 2,4-DNP, and gives a fuchsia color with the Schiff test. 6. In each of the following cases, describe the next test you would perform. (a) Unknown X is insoluble in water, 5% NaOH, 5% HCl, and conc. H2SO4. (b) Unknown Y is insoluble in water, soluble in 5% NaOH, and insoluble in 5% NaHCO3. (c) Unknown Z is insoluble in water, insoluble in 5% NaOH, insoluble in 5% HCl, and soluble in conc. H2SO4. 7. If your unknown is soluble in water and does not produce bubbles with 5% NaHCO3, what steps would you follow to determine if your unknown is an amine? Post-Laboratory Questions 1. Record the solubility results for each unknown that you tested. Describe your observations and briefly explain your conclusions. 2. Record the results of the classification tests that you conducted for each unknown you tested. Describe your observations and briefly explain your conclusions. 3. For each of your unknowns, list the functional group to which it belongs next to its identification code. 4. You suspect that your unknown contains halogen, so you perform the silver nitrate in ethanol test and the sodium iodide in acetone test, both of which are negative. Do these results prove that your compound does not contain a halogen? Briefly explain.

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Experiment 3: esterification ESTERIFICATION

Introduction:

Esters are a class of organic compounds which, unlike many organics, have pleasant odors. In fact, many of the "artificial flavors" used in food products are esters - very pure esters.

Esters occur naturally but can also be synthesized in the lab. To synthesize an ester, you must start with two other organic compounds - an alcohol and an acid. The ester is formed when dehydration occurs. The alcohol and acid react to form the ester and a water molecule.

Some esters that can be synthesized include methyl salicylate (oil of wintergreen), isoamyl butyrate (pear), isoamyl acetate (banana), ethyl acetate (fruity), and ethyl salicylate (sweet smell).

Purpose:

The purpose of this experiment is to synthesize and identify four esters.

C

H 3C O

O

H

H +

C +

O

O

H

H

H 3C

+H 2C

H 3C OH

H +

C

H3C

OH

OH

O + H

CH 2

H3C

C

H3C

OH

OH

O

CH 2

H3C

H +C

H 3C

O +

OH

O

CH 2

H3C

HH

C

H3C O

O +H

CH 2

H3C

+H2OC

H 3C O

O

CH 2H 3C

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Equipment/Materials:

hot plat Dowex 50 x 2 - 100 ion-exchange resin

250 mL beaker glacial acetic acid (20 mL)

styrofoam cups (4 per group) salicylic acid (10 g)

Beral pipet (1 per group) isoamyl alcohol (15 mL)

microscale thermometers methanol (20 mL)

labelling tape ethanol (15mL)

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Safety

Always wear safety glasses and an apron. Keep all reactants away from flames. Do not smell chemicals by placing your nose at the bottle’s opening; waft the

smell toward your nose with your hand. Never eat or drink in the lab.

Procedure:

1. Heat water in a beaker on a hotplate near a wall. Place a microscale thermometer in the water. Monitor the temperature – it should stay between 70 – 80 oC.

2. Label 4 microscale test tubes A – D at the top with labeling tape. The test tubes may be placed in microscale Erlenmeyer flasks, which will act as stands for the test tubes.

3. Use the microspatula to place a small amount of ion-exchange resin (about

equal to two garden peas) into the four test tubes.

4. Place the following in the test tube labeled “A”:10 drops of isoamyl alcohol

10 drops of glacial acetic acid

5. Place the following in the test tube labeled “B”:

10 drops of ethanol

10 drops of glacial acetic acid

6. Place the following in the test tube labeled “C”:

salicylic acid – a similar amount to the resin

enough methanol to dissolve the acid (about 25 drops)

7. Place the following in the test tube labeled “D”:

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salicylic acid – a similar amount to the resin

10 drops of ethanol

8. Place all four test tubes in the water bath on the hot plate, and allow them to react for 10 minutes. Be sure that the test tubes are aimed at the wall. (It is not necessary to put the Erlenmeyer flasks in the water.)

9. After 10 minutes, CAUTIOUSLY smell the odor of each. Remember to waft the smell towards your nose. What do you smell? Record on the data table.

10. Pour the liquid contents of tube A into a clean styrofoam cup. Swirl the cup one or

two times, then immediately pour the excess reactants into a sink, and rinse with a

small amount of water. Smell the inside of the cup. Record what you smell.

11. Repeat step 10 for the examination of the other three esters.

12. Thoroughly rinse out each of the test tubes and cups.

Data Table:

TUBE SMELL INITIAL SMELL AFTER RINSING

A __________________________ ________________________

B __________________________ ________________________

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C __________________________ ________________________

D __________________________ ________________________

Questions:

1. Tube A contained the following:

___________________smell or ___________________ester

2. Tube B contained the following:

___________________smell or ___________________ester

3. Tube C contained the following:

___________________smell or ___________________ester

4. Tube D contained the following:

___________________smell or ___________________ester

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5. How did the smell of each ester change after rinsing with water?

6. What name would you give to an orange-smelling ester formed by adding octanol to

acetic acid?

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ESTERIFICATION

TEACHER NOTES

STANDARDS MET:

3.4.7.A - Describe concepts about the structure and properties of matter.

Describe and conduct experiments that identify chemical and physical properties.

3.2.10.C – Apply the elements of scientific inquiry to solve problems.

Conduct a multiple step experiment. 3.4.10.A – Explain concepts about the structure and properties of matter.

Explain the formation of compounds and their resulting properties usingbonding theories (ionic and covalent).

Understand that carbon can form several types of compounds. 3.7.12.A – Apply advanced tools, materials and techniques to answer complex

questions.

Demonstrate the safe use ofcomplex tools and machines within their specifications.

Evaluate and use technological resources to solve complex multistepproblems.

Lab Time: 45 minutes

Answers to Questions:

1. Tube 1 contained the following:

___banana__________smell or __isoamyl acetate____ester

2. Tube 2 contained the following:

_____fruity________smell or __ethyl acetate_____ester

3. Tube 3 contained the following:

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____wintergreen____smell or _methyl salicylate__ester

4. Tube 4 contained the following:

___sweet___________smell or __ethyl salicylate__ester

5. How did the smell of each ester change after rinsing with water?

Smell should have become stronger because “harsh” un-reacted chemicals were

washed away.

6. What name would you give to an orange-smelling ester formed by adding octanol to

acetic acid?

octyl acetate

Considerations:

This lab is a version of one developed by Brother Carmen Ciardullo (Micro Action Chemistry , Flinn Scientific inc., 1990). This book contains a wealth of microscale experiments and is suggested for any teacher who is considering incorporating microscale labs into a chemistry class. One change from the original procedure is to rinse the reactants in a cup and then rinse one time with water. This seems to allow the esters to be smelled much easier due to the increased surface area and the removal of harsh “masking” chemicals.

Students will be using concentrated acids so caution must be maintained at all times. Caution should be taken while heating the tubes. Students can also make other esters using this equipment but, as with any lab, the instructor should first experiment to determine if results are acceptable and safety is maintained. The production of the esters can be verified using gas chromatography (see Verification of Esterification.

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Experiment 4: Nitration of Aromatic compounds:

Purpose Study electrophilic aromatic substitution reaction (EAS) Study regioselectivity for EAS reactions Chemicals Materials 150 – mL beaker Methyl benzoate 400-mL beaker Sulfuric acid (conc.) 125-mL flask Nitric acid (conc.) Stirring rod Ice Mel-temp Methanol Suction filtration funnel Introduction Unlike nucleophilic substitutions, which proceed via several different mechanisms, electrophilic aromatic substitutions (EAS) generally occur via the same process. Because of the high electron density of the aromatic ring, during EAS reactions electrophiles are attracted to the ring's π system and protons serve as the leaving groups. Equation 1. During SN1 reactions, however, nucleophiles attack an aliphatic carbon and weak Lewis bases serve asleaving groups

Generally, EAS reactions occur in three steps, Scheme I. During Step I, the electrophile is produced, Scheme I

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,

Usually, by the interaction of a compound containing the potential electrophile and a catalyst. During Step II, the aromatic π system donates an electron pair to the electrophile, forming a σ bond ( an arenium cation) followed by deprotonation in step III in the present of a base ( HSO4-) affording the substituted arene. EAS reactions are generally second-order processes, i.e., first order in electrophile and first order in arene. Thus, Step II. is the rate-determining step (rds); rate = k2 [arene][electrophile]. Electrophilic Aromatic Substitution: Nitration of Methyl Benzoate Benzene rings are components of many important natural products and other useful organic compounds. Therefore, the ability to put substituents on a benzene ring, at specific positions relative to each other, is a very important factor in synthesizing many

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organic compounds. The two main reaction types used for this are both substitutions: Electrophilic Aromatic Substitution (EAS) and Nucleophilic Aromatic Substitution (NAS). The benzene ring itself is electron-rich, which makes NAS difficult, unless there are a number of strongly electron-withdrawing substituents on the ring. EAS, on the other hand, is a very useful method for putting many different substituents on a benzene ring, even if there are other substituents already present. Electrophilic Aromatic Substitution chapter describes the factors involved in the regioselectivity for EAS reactions using benzene rings, which already have substituents on them. In this experiment you will put a nitro (—NO2) group on a benzene ring, which already has an ester group, attached to it (methyl benzoate). The actual electrophile in the reaction is the nitronium ion (NO2+), which is generated in situ ("in the reaction mixture" HNO3/H2SO4) using concentrated nitric acid and concentrated sulfuric acid. Reaction:

Experimental Procedure In a 125-mL. Erlenmeyer flask mix 1.5 mL of methyl benzoate and approximately 4.0 mL of concentrated sulfuric acid (drop-wise), and chill it in an ice bath. Continue to cool the mixture in the ice bath to reduce the heat, which produced in the reaction. After complete addition of sulfuric acid, add approximately 2.0 mL concentrated nitric acid (measured in 10- mL graduated cylinder) drop- wise using a small graduated plastic pipette and mix by gentle swirling. Continue to cool the reaction mixture. Allow the reaction mixture to stand at room temperature for about five minutes. Float the 125-mL flask in a 400-ml beaker hot water bath. Remove the flask occasionally and swirl the content carefully. After fifteen minutes heating pour the reaction mixture in 100-ml of ice water contained in a 150- mL beaker, with stirring. Product Isolation- Isolate the product by vacuum filtration, wash the product with (ice) cold water (20 mL). Note - Proper washing removes the more soluble ortho isomer. The crude material may be purified by recrystallization from a small volume ( ~ 10 mL) of hot methanol (optional). The crude product is pressed dry. You may need to air dry (or hand dry using paper towels) the product. Discard the aqueous filtrate down the drain with lots of water.

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Determine the weight, melting point, and percentage yield. Pure methyl m-nitrobenzoate melts at 78.5oC. Submit the product to your instructor in a paper wrapped and labeled including your name(s).

Nitration of Aromatic Compounds: Preparation of methyl-m-nitrobenzene REPORT FORM Name _______________________________ Instructor ___________________________

Date ________________________________

Calculation (please show your calculations on results of laboratory report) 1. Weight of methyl benzoate ________ g ________ moles 2. Theoretical yield of methyl m-nitrobenzoate ________ g ________ moles 3. Weight of methyl m-nitrobenzoate ________ g ________ moles 4. Percentage yield of methyl m-nitrobenzoate ________ % 5. Melting point range of product _____________ 0C 6. Literature melting point of methyl m-nitrobenzoate _____________ 0C

Nitration of Aromatic Compounds Due before lab begins. Answer in space provided. 1. Which is nitrated faster? toluene or nitrobenzene? Explain. 2. Indicate the product formed on (mono) nitration of each of the following compounds: a) Cyanobenzene (benzonitrile) b) toluene c) benzoic acid. 3. Why is methyl m-nitrobenzoate formed in this reaction instead of o- and p-? What product would you expect if methyl benzoate underwent dinitration? 4. Methyl-m-nitrobenzoate is an excellent (identification) derivative of methyl benzoate. What are the properties of methyl-m-nitrobenzoate that makes it an excellent derivative of the starting ester? . 5. List three combinations of reagents used for nitration of aromatic compounds?

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Experiment 5: The synthesis of Aspirin ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

Synthesize aspirin from its corresponding acid anhydride and alcohol Compare two different synthetic routes for the preparation of esters

Relates to chapter 11 of “Essential Organic Chemistry, 2nd Ed.”.

APPARATUS AND CHEMICALS

INTRODUCTION

The classic synthesis of esters is the Fischer-Speier esterification, employed in experiment 1. However, several other methods are available, one being often favored other another depending on the problems needing to be tackled. The method used in this experiment is the alcoholysis of an acid anhydride. Alternative methods are the following:

- alcoholysis of acyl chlorides

- Steglish esterification

- transesterification

- Favorskii rearrangement of α-haloketones in presence of base

- nucleophilic displacement of alkyl halides with carboxylic acid salts

- Baeyer-Villiger oxidation of ketones with peroxides

- Pinner reaction of nitriles with an alcoholAlcohols react with acyl chlorides or acid anhydrides to give esters:

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These reactions are irreversible, thus simplifying workup. Since acyl chlorides and acid anhydrides react also with water, anhydrous conditions are preferred. The analogous acylation of amines that produces amides is less sensitive towards water because amines are stronger nucleophiles and react more rapidly.

PROCEDURE

In a 50 mL beaker, introduce salicylic acid (2 g) and acetic anhydride (3 mL). Then, add 1 drop of concentrated sulfuric acid and stir the mixture. Heat by means of a bain-marie for 15 min while strirring continually with a glass rod.Add 35 mL of water, swirl the mixture and carry out a vacuum filtration. Weigh the mass of crude product (aspirin) obtained.

The crude acetylsalicylic acid is purified by recristallisation. It is dissolved in hot methanol or ethanol (6 mL). The resulting solution is poured into 20 mL of hot water. If a precipitation occurs, heat the mixture until complete dissolution and then let it cool down slowly (in the air, next water, then ice water). After recrystallisation, the solid is filtered and dried. Weigh the mass of pure product (aspirin) obtained.

R

O

Cl + R' OH R

O

OR'

+ HCl

R

O

O + R' OH R

O

OR'

+R

O

R

O

OH

REACTION

httpwww2.volstate.edu/chem/1110/Labs/Synthesis_of_Aspirin.htm

+ O

OO H2SO4

50-60 oC, 15 min

OH

O

OH

O

O

OH

O

salicylic acid acetic anhydride acetylsalicylic acid(aspirin)

+OH

O

acetic acid

Compound M.W. (g/mol) Density (g/mL) b.p (oC)

Salicylic acid 138.12 / 211 Acetic anhydride 102.09 1.08 138-140 Sulfuric acid, 98 % 98.08 1.84 ~ 290 Aspirin 180.16 / /

25

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Experiment 6: Synthesis of Hexahydro-1m3m5-tri-p-tolyl-s-triazine.

Materials:

p-toluidine 10gm

aqueous formaldehyde (40%) 15ml

Ethanol 50ml

Petroleum ether 60ml

Procedure:

1- in 100ml conical flask dissolve p-toluidine in ethanol at room temperature.

2- Add aqueous formaldehyde (40%). 3- Leave the mixture for ( 30 mint) for the precipitate to formed. 4- Filter the product on boughner and wash with cold ethanol. 5- Put the product in conical flask and add boiling petroleum ether. 6- Filter the white crystals. 7- Dried the white crystals. 8- Determine the precent yielid.

formaldehyde p-toluidine

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Experiment 7: : synthesis of glocosazone

materials:

procedure:

1-In conical 1 dissolve 5gm glucose in 25ml of boiling water.

2- In conical 2 dissolve glacial acetic acid in 25ml of water then add 10ml phenyl hydrazine shake well until the solution of phenyl hydrazine acetate is formed.

3-Add solution in conical 1 to solution in conical 2 and stir very well.

4- Boil the solution un water bath the yellow ozazone wel formed after 15 minutes.

5- Continue heating for 45 minutes.

6-Cool the solution untile the yellow crystals formed.

7- filter the partecepate then wash with water and ethanol.

8- Dry the patecepate then weigh it.

9-calculate the yield percent.

O

5 gm -

- 10ml

- 10ml

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Experiment 8: synthesize triphenylmethanol from benzophenone via Grignard reaction. The product will be isolated through extractions and purified by recrystallization. Reaction efficiency will be evaluated through percent yield, percent recovery, and the purity of the final product will be determined by IR, TLC, and mp determination. Chemicals: bromobenzene, magnesium turnings, diethyl ether, benzophenone, biphenyl, triphenylmethanol, iodine, 6 M HCl, brine, anhydrous MgSO4 or Na2SO4, 10:90 EtOAc/hexanes. Glassware and equipment: 100 mL RBF, air condenser, Claisen adaptor, 60 and 125 mL addition funnel, short stem glass funnel, two 50 mL Erlenmeyer flasks, 10 mL graduated cylinder, lab jack, crystallizing dish, magnetic stir bar. Techniques: reflux, extraction, vacuum filtration, recrystallization, TLC, mp, IR spectroscopy. Introduction In 1912 Victor Grignard received the Nobel prize in chemistry for his work on the reaction that bears his name, a carbon-carbon bond-forming reaction by which almost any alcohol may be formed from appropriate alkyl halides and carbonyl compounds. The Grignard reagent RMgBr is easily formed by redox reaction of an alkyl halide with magnesium metal in anhydrous diethyl ether solvent. R-Br + Mg →RMgBr The Grignard reagent can be viewed as an ionic species consisting of carbanion R-, with Mg2+ counterion and an additional Br- counterion. The carbanion R- is very reactive, and functions both as an extremely strong base andan extremely strong nucleophile. Please review the mechanism of this reaction for your reference. Byproducts 1. Biphenyl, Ph-Ph, which is formed in competition with the Grignard reagent PhMgBr. Following initial electron transfer, the phenyl radical Ph• can either accept another electron leading to the desired carbanion, or combine with another phenyl radical to make biphenyl. This product is formed as a result of quick addition of bromobenzene to magnesium turnings

2. Benzene (Ph-H), resulting from protonation of the carbanion. The carbanion is very basic, so if there is any water in the solvent or in the glassware, or if moist air is allowed to enter the reaction mixture, some of the carbanion will be protonated. Formation of this product results from presence of any moisture in the reaction mixture: so, please, do not sneeze, cough, or spit on your reaction!!!

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3. Activation of magnesium: Pure magnesium is an active metal, so active that any magnesium that has been exposed to air is inevitably coated with a film of magnesium oxide on its surface. This oxide film blocks the bromobenzene from actually contacting active magnesium, and thus prevents the requisite electron transfer. One way to expose active surface is to simply break several turnings before placing them into reaction flask. The other way is to break the turning inside the flask using your glass stirring rod: this procedure is not the safest as it often results in breaking the fragile glassware. The third way is addition of an activator such as a small iodine crystal. The iodine serves two functions. a. The first is as an indicator. The color will disappear when the magnesium is activated and is able to do redox chemistry with bromobenzene. b. The second is as an activator. Iodine is sometimes able to chemically “clean” the surface of the magnesium so that fresh, active magnesium is exposed so that it can do redox chemistry with bromobenzene. However, it doesn’t often work! 4. Unreacted starting material (Could be the Ph-Br, the Mg, and/or the ester). Experimental: First class period, Step 1: Preparation of the Grignard Reagent Glassware needed for the first reaction setup: please wash and dry during the previous class period and store in your drawer. a. 100-mL RBF b. “Claisen” adapter c. Air condenser d. 125mL separatory funnel with stopper e. Two 50mL Erlenmeyer flasks f. 10 mL graduated cylinder The reaction must be done in the hood!!! 1. Clamp the 100-mL round-bottomed flask equipped with a stir bar to a vertical rod using a two-finger clamp. 2. Weigh out about 0.5g of magnesium metal. (Record weight) 3. Break a couple of magnesium turnings, pour them into RBF, add 10 mL of diethyl ether and place Claisen head into the joint. 4. Add 125 mL sep funnel on one side and the air condenser to the other joint of the Claisen head. Clamp the glassware with keck clamps. Temporary stopper both outlets. 5. Pour 20 mL of ether into the separatory funnel and put stopper back on. 6. Measure out 2.1 mL of bromobenzene in a graduated cylinder. Record the volume as accurately as possible. Transfer it to a clean stoppered 50mL EF. Measure about 10mL anhydrous diethyl ether into the same cylinder, transfer again into the same EF. Swirl the flask and add about half of the mixture into the 100mL RBF with magnesium turnings. The rest of the mixture goes into the separatory funnel attached to the RBF. Rinse the graduated cylinder with about 7mL of anhydrous ether and add it to the mixture in the separatory funnel. 7. Initiate the reaction in the RBF by carefully shaking the flask. If the redox chemistry of the Grignard reaction initiates, the iodine color will go away, the solution will begin to get hot, there will be some bubbling, and solution may become slightly cloudy.

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8. Slowly drain the bromobenzene/ether/iodine solution into the round-bottomed flask. Shake the RBF occasionally to speed up the reaction. Add additional 1-2mL anhydrous ether to the separatory funnel to rinse off the mixture, and drain it to the RBF. Stopper the separatory funnel. 9. The reaction should be so exothermic that it will be self-boiling for some time. If the rate of boiling subsides, apply a heating mantle (connected to the variac, not directly to the wall outlet) and apply heat to maintain a good rate of boiling. Do not exceed power setting of 20-25. The color of solution should turn brown. If it becomes heterogeneous and greenish-brown, your reaction mixture has absorbed moisture, and your yields will suffer tremendously. 10. Maintain boiling until most of magnesium metal has reacted. Since diethyl ether has a low boiling point, you might need to replenish the solvent to prevent the reaction mixture from drying. Add diethyl ether through air condenser using a clean dry pipette. Grignard

Step 2: Reacting the Grignard Reagent with Benzophenone 1. After the hour of reflux is up, let the reaction cool down (an ice-water bath might help). 2. Mix 2.4g benzophenone with 10mL of ether in a clean 50mL EF and add the mixture to your separatory funnel. (Stopcock closed). 3. Remove the cold bath (if you have one on), then drain the ketone/ether solution into the RBF as rapidly as possible but make sure that the reaction doesn’t overheat too much. Try to shake the solution around as much as possible (hard to do when it’s clamped!) If things start to boil hard, reapply the cold bath. 4. If everything is added without excessive boiling, try to shake everything up, and give it five minutes to continue reacting. The reaction should take approximately 15 min. 5. If the reaction is still hot, cool it with the ice bath. 6. Add about 20 grams of ice and about 7-8mL 6M hydrochloric acid. The acid will react exothermically with both the anion and unreacted magnesium. The ice is there simply to absorb the heat.

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7. Swirl well to promote hydrolysis and break the solid clumps. Use a spatula to break up the chunks. You should obtain two distinct layers: top organic layer with the product and bottom aqueous layer with MgBrOH and excess acid. Since the process is exothermic, some ether might be lost during the reaction, so add excess ether if necessary to maintain about 10mL of volume for the top layer. 8. Pour the mixture into your cleaned 125mL separatory funnel. (The magnesium doesn’t need to be totally dissolved) 9. Vent, swirl, and drain the bottom layer into a beaker. 10. Transfer the top layer into a different labeled Erlenmeyer flask, return the aqueous layer into the separatory funnel and re-extract it with additional 10 mL ether. 11. Discard the aqueous layer into aqueous waste container located in the waste hood. 12. Combine the organic layers, wash with brine, add about 1.0 g anhydrous sodium sulfate or other drying agent, stopper, parafilm, label with your name and leave it on the tray provided by your instructor. Second Class Period: Purification and Characterization of Product 1. Decant the organic dried solution into pre-weighed 50mL dry RBF. Rotary-evaporate the solution to obtain crude brownish oily product. 2. Obtain the crude yield and record the percent yield. Save a couple of crystals in a labeled test tube (CP1) for TLC analysis. This product contains triphenylmethanol and biphenyl byproduct. This byproduct can be removed by simply dissolving your crude mixture in about 10 mL of warm petroleum ether (bp 30-60oC). After the mixture cools down to room temperature, transfer it on an ice bath for 5 min and then vacuum filter the solution. Wash the crystals with some ice-cold petroleum ether (use pipette towash crystals). 3. Record the crude yield after the product is dried. Save acouple of crystals in a labeled test tube for TLC analysis (CP2), and save some of the mother liquor for the same purpose (BP). 4. Recrystallize the crude product from hot isopropyl alcohol. Record the pure yield and percent recovery from CP1. Save a couple of crystals in a labeled test tube for TLC analysis (PP). Make a TLC plate with six pencil marks for six tracks ready: 5. Run the TLC in 10:90 EtOAc/hexane mixture. Solutions of authentic materials will be provided (do not remove the spotters from these solutions to prevent contamination). 6. Mark down the results, calculate the Rf values, and answer the following questions: solvent trap Buchner funnel connect to water aspirator filter flask

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filter flask Fig. 3. Vacuum filtration apparatus Is biphenyl present in the crude mix? In the purified material? Is methyl benzoate present in the crude mix? In the

purified material? Any other side products in the crude? Did recrystallization purify the material at all? Did crystallization get all of the product out of the

solvent? 7. Take a melting point of your final product (literature value 162oC). 8. Take IR spectrum of the purified product (dissolve a couple of crystals in methylene chloride). 9. Transfer the purified product in a labeled vial, secure

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with rubber band and place in the tray provided for grading.

Guidelines for Formal Report: (20 pt) Note: Attach all specra and label the important peaks (Draw the structures, label the functional groups or H, C, and match them with the speactra). Severe point deduction will follow if spectral data is missing. Abstract (2 pt) Target molecule and the reactions with mechanisms (2 pt) Tabulated results (6 pt):

Discussion: Yields: Explain what could affect the yield on each step. Be specific and refer to your notebook. Melting points: Discuss the melting points in reference to the literature values and comment on the results via purity of the product. TLC: compare the TLC of the products and comment on the presence of the starting materials and any impurities observed. Tie this up with your yields and the meling points: your data should relate very closely. IR and NMR: when reporting IR and NMR of the products, please do not just list the chemical shifts and the wavenumbers on NMR and IR but rather comment on the changes from one compound to another in terms of reporter peaks. The NMR’s of the starting material and the product are presented below:

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Conclusion (2 pt): comment on any disadvantages or failures of this experiment and propose modifications/improvements for the synthetic procedure. Please be specific and note that general comments such as ‘use a different solvent, different glassware, etc’ are not valid to make your point!