CHM 2322 (Organic Chemistry Lab II)

I. Pre-Lab Report

A. Introduction

The purpose of this experiment is to convert aniline to 1-bromo-3-chloro-5-iodobenzene via a six step synthesis reaction that for the most part involves electrophillic aromatic substitution. First, aniline will be converted to acetanilide using acetic anhydride. Next, bromine will be added to acetanilide in a solution of acetic acid to yield 4-bromoacetanilide. Then, chlorine will be introduced to 4-bromoacetanilide again in a solution of acetic acid to produce 4-bromo-2-chlroracetanilide. An acid-catalyzed hydrolysis will then take place to convert 4-bromo-2-chlroracetanilide to 4-bromo-2-chlroracetaniline using hydrochloric acid in ethanol. Iodine will then be added to the molecule using iodine monochloride in the presence of acetic acid to yield 4-bromo-2-chloro-6-iodoaniline. Last, the 4-bromo-2-chloro-6-iodoaniline will be converted to 1-bromo-3-chloro-5-iodobenzene. This will take place by removing the amino group using nitrous acid to diazotize and hypophosphorous acid.

PART I

B. Main Reaction

Aniline —> 1-Bromo-3-chloro-5-iodobenzene

C. Mechanism

The overall reaction takes place using a six step synthesis reaction. Most of the reactions involve electrophillic aromatic substitution. Refer to the attached sheet for the reaction mechanism of the conversion of aniline to acetanilide.

D. Side Reactions

There are no side reactions.

E. Table of Reactants and Product(s)

Part II

B. Main Reaction

Acetanilide + Br₂ + CH₃CO₂H —> 4-Bromoacetanilide + 2-Bromoacetanilide + HBr

C. Mechanism

The substituent on the benzene ring, –NHCOCH₃,is a ring activating group and thus is ortho and para directing. This allows bromination to occur at ortho and para positions. Refer to the attached sheet for the reaction mechanism of the conversion of acetanilide to 4-bromoacetanilide.

D. Side Reactions

To get rid of excess bromine, this sodium bisulfate is added to produce this reaction: HSO₃^– + Br₂ + 3H₂O —> HSO₄^– + 2 Br^– + 2H­₃O^–

E. Table of Reactants and Product(s)

Part III

B. Main Reaction

4-Bromoacetanilide + Cl₂ —> 4-Bromo-2-chloroacetanilide + HCl

C. Mechanism

The substituents on the benzene ring, –NHCOCH₃ and –Br,are both ortho and para directors. However, –NHCOCH₃ is an activating group while –Br is mildly deactivating, so this favors chlorine addition ortho to –NHCOCH₃. Refer to the attached sheet for the reaction mechanism of the conversion of 4-bromoacetanilide to 4-bromo-2-chloroacetanilide.

D. Side Reactions

HCl + NaClO₃ —> HClO₃ + NaCl

2NaCl + 2H₂O —> Cl₂ + H₂ + 2NaOH

E. Table of Reactants and Product(s)

Part IV

B. Main Reaction

4-Bromo-2-chloroacetanilide + HCl + H₂O + CH₃CH₂OH —> 4-Bromo-2-chloroanilinium chloride

4-Bromo-2-chloroanilinium chloride + NaOH + H₂O —> 4-Bromo-2-chloroaniline + NaCl + H₂O

C. Mechanism

Refer to the attached sheet for the reaction mechanism.

D. Side Reactions

There are no side reactions during this part of the synthesis.

E. Table of Reactants and Product(s)

Part V

B. Main Reaction

4-Bromo-2-chloroanilinium chloride + ICl + CH₃CO₂H —> 4-bromo-2-chloro-6-iodoaniline

C. Mechanism

The reaction takes place via Sn2 substitution. Refer to the attached sheet for the reaction mechanism.

D. Side Reactions

There are no side reactions during this part of the synthesis.

E. Table of Reactants and Product(s)

II. Post-Lab Report

Part I – Steps 1 Through 3

A. Experimental Procedure

The experimental procedure was followed pretty much as written. One change throughout was that the amount of reagents needed for the procedures had to be proportional to the amount of product recovered. Another change throughout was that the melting point of the products were never taken and a small sample was never submitted. During acetylation, acetic anhydride was not added to the filtrate to try to recover additional acetanilide. During bromination, 3 mL of methanol per gram of compound was added during recrystallization rather than 5 mL. Also, the bromine used was a weaker concentration than anticipated, so additional store-bought 4-bromoacetanilide was added to the product recovered. Finally, during chlorination, an excess of methanol was added while washing the beaker to filtrate the recrystallized product, so an excess of cold water was added to the filtrate to recover more 4-bromo-2-chloroacetanilide.

B. Observed Yield of Product

Weight of aniline: 4.7 g

Moles of aniline: 0.05

Observed weight of acetanilide: 5.122 g

Observed moles of acetanilide: 0.038

Observed yield of acetanilide from aniline: 76.0%

Theoretical weight of acetanilide: 6.76 g

Theoretical moles of acetanilide: 0.05

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Observed weight of 4-bromoacetanilide: 4.7 g

Observed moles of 4-bromoacetanilide: 0.022

Observed yield of 4-bromoacetanilide from acetanilide: 57.9%

Theoretical weight of 4-bromoacetanilide: 8.13 g

Theoretical moles of 4-bromoacetanilide: 0.038

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Observed weight of 4-bromo-2-chloroacetanilide: 4.0 g

Observed moles of 4-bromo-2-chloroacetanilide: 0.016

Observed yield of 4-bromo-2-chloroacetanilide from 4-bromoacetanilide: 72.7%

Theoretical weight of 4-bromo-2-chloroacetanilide: 5.47 g

Theoretical moles of 4-bromo-2-chloroacetanilide: 0.022

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Observed yield of 4-bromo-2-chloroacetanilide from aniline: 32%

C. Calculations

(Moles of final product) / (Moles of starting material) * 100 = Observed yield

Moles of starting material = Theoretical moles of product

D. Conclusions

During these first three parts of the six-step synthesis, it was really important to do everything very deliberately and carefully. It was necessary to make sure every step was performed with precision in order to get a high yield in the end. If lab procedure was not followed exactly as described, product would most likely be lost. There are many factors that can lead to loss of eventual final product. Such factors include adding too much methanol during recrystallization, not using the precise amount of reagents required, and simply not being able to get all of the solutions and products transferred from filter paper to flask or from flask to flask. One of example of something that did happen during the synthesis that affected the yield was during bromination. The bromine used during bromination turned out to be of lesser concentration than expected, which gave a poor yield of product. This was uncontrollable, and store-bought 4-bromoacetanilide had to be added to the recovered product. The store bought 4-bromoacetanilide is not as pure as the recovered product, so this will affect the yield of product in the next steps of synthesis. Overall, precision was the most important factor in recovering a high percent yield.

The percent yields for the synthesis thus far are fairly low. From step to step, the average percent yield has been 68.9% and overall the percent yield from the beginning until the last completed step in the synthesis has been 32%. It is expected that the percent yield will keep going down from after each step because it is very hard to achieve a very high yield under the laboratory conditions. Under perfect conditions, the expected percent yield would be 100%, but is nearly impossible to accomplish that. The observed yield after each separate step does not seem very bad, with the average being nearly 70%, but that loss of product will add up over the course of the six steps. The theoretical moles for the product of each step is equal to the number of moles for the starting material because the starting material reacts to form the product in a 1:1 ratio for each step.

Part II – Steps 1 Through 6

A. Experimental Procedure

The experimental procedure was followed pretty much as written. One change throughout was that the amount of reagents needed for the procedures had to be recalculated to be proportional to the amount of product recovered. Another change throughout was that the melting point of the products were never taken and a small sample was never submitted. During amide hydrolysis, a second crop of 4-bromo-2-chloroaniline was not collected, which would have been performed by adding additional cold water to the filtrate. During iodination, a second crop of product was again not collected, which would have been performed by the same method described during amide hydrolysis.

B. Observed Yield of Product

Weight of 4-bromo-2-chloroacetanilide: 4.0 g

Moles of 4-bromo-2-chloroacetanilide: 0.016

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Weight of 4-bromo-2-chloroaniline: 2.142 g

Moles of 4-bromo-2-chloroaniline: 0.010

Observed yield of 4-bromo-2-chloroaniline from 4-bromo-2-chloroacetanilide: 62.5%

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Weight of 4-bromo-2-chloro-6-iodoaniline:

Moles of 4-bromo-2-chloro-6-iodoaniline:

Observed yield of 4-bromo-2-chloro-6-iodoaniline from 4-bromo-2-chloroaniline:

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Observed yield of 4-bromo-2-chloro-6-iodoaniline from 4-bromo-2-chloroacetanilide:

Observed yield of 4-bromo-2-chloro-6-iodoaniline from aniline: 0.05 moles aniline

C. Calculations

(Moles of final product) / (Moles of starting product) * 100 = Observed yield

D. Conclusions

The percent yield through the first five steps of the synthesis is %. This percentage is fairly low, but the percent yield for the sixth step, deamination, is typically very low, so this would make the overall percent yield even lower. Even with a typical low yield for deamination, it is most likely that some final product would have been recovered if deamination had taken place. Amide hydrolysis and iodination were performed very carefully and precisely, but the yields were still not very high. This shows how hard it can be to achieve high yields during a synthesis in laboratory conditions.

The theoretically yields from starting material to product should have been a 1:1 mole ratio throughout the synthesis. These theoretical yields were not nearly achieved however, for various reasons. The steps where the most product was lost were during transfers and recrystallization. It was difficult to transfer every bit of product between filter paper and flasks. During recrystallization, product could have easily evaporated away if the product in methanol was heated too much. It was difficult to control and measure the heat during this step.

Amide hydrolysis was performed so that iodine would be directed ortho to the previously acetamido group during iodination. The amino group generated during amide hydrolysis is more activating than the acetamido group. Iodine is less electrophilic than bromine and chlorine, so it needed a more activating ring in order to attach. The acetamido group was better for bromination and chlorination because they required a less activated ring and the reaction could be controlled to give monosubstitution. There was no possibility of disubstitution during iodination with the amino group present.

I. Pre-Lab Report

A. Introduction

The purpose of this experiment is to convert benzoic acid to methyl benzoate via an acid catalyzed reaction with methanol. The reaction will be prepared by Fischer esterification, which involves the reaction reaching equilibrium after refluxing for a few hours. The purity of the benzoate will then be determined using infrared spectroscopy.

B. Main Reaction

Benzoic Acid + Methanol —> Methyl Benzoate + Water

C. Mechanism

Refer to the attached sheet.

D. Side Reactions

There are no side reactions.

E. Table of Reactants and Product(s)

II. Post-Lab Report

A. Experimental Procedure

The experimental procedure was followed pretty much as written. One change made was that an additional 15 mL of dichloromethane was added to the final dichloromethane solution because it was too concentrated. The one other change was that the IR spectrum of methyl benzoate was not taken.

B. Observed Yield of Product

Weight of benzoic acid: 10.008 g

Weight of distilled methyl benzoate: 6.274 g

Percent recovery: 62.69%

C. Calculations

(Weight of distilled methyl benzoate) / (Weight of benzoic acid) * 100 = Percent recovery

D. Conclusions

The percent recovery of methyl benzoate for the experiment was 62.69%. The theoretically yield for the experiment is 85%, so the percent recovery was low. Different factors could have contributed to this. First off, a small amount of the weighed benzoic acid did not make into the 100 mL round-bottomed flask. This means the actual starting amount was slightly lower than measured. While separating the layers, it gauge when to close the stopcock perfectly, so that led to a loss of eventual product. Also, while separating the layers, there was some emulsion during mixing, so again eventual product may have been lost because the layers did not completely separate. Lastly, if the concentration of methanol was higher, that would have also led to a higher percent yield.

If water was removed from the reaction mixture, it was cause equilibrium to shift towards methyl benzoate to make water and thus lead to an increased conversion of benzoic acid to methyl benzoate. When a compound on one side of the reaction is removed, equilibrium will shift towards the side it was removed from. If more of a compound is added to one side, then equilibrium will shift towards the other side.

I. Pre-Lab Report

A. Introduction

The purpose of this experiment is to investigate the influence of molecular structure on the reactivity of an alkane in free-radical chlorination using gas chromatography. The alkene to be used, 1-chlorobutane, will be reacted with sulfuryl chloride to produce four isomeric dichlorobutanes. The reaction will take place using a similar apparatus described in figure 18.1 of Williamson. The product will be washed and dried, then analyzed with a gas chromatograph.

B. Main Reaction

1-Chlorobutane + Sulfuryl Chloride –> 1,1-Dichlorobutane + 1,2-Dichlorobutane + 1,3-Dichlorobutane + 1,4-Dichlorobutane

C. Mechanism

The reaction proceeds with via free radical chlorination. Refer to the attached sheet to see the detailed mechanism.

D. Side Reactions

There are no side reactions.

E. Table of Reactants and Product(s)

II. Post-Lab Report

A. Experimental Procedure

The experimental procedure was followed exactly as written. The only minor difference was that 6 mg of AIBN was used instead of the recommended 4 mg. Also, it was noted that during washing, there was a bubble in the organic layer which may have caused error.

B. Observed Yield of Product

Tared vial: 11.568 g

Tared vial with organic product: 11.648 g

Organic product recovered: 0.080 g

C. Calculations

7.8% 1,1-dichlorobutane / 2 H = 3.9% per each primary H

22.7% 1,2-dichlorobutane / 2 H = 11.35% per each secondary H

44.4% 1,3-dichlorobutane / 2 H = 22.2% per each secondary H

25.1% 1,4-dichlorobutane / 3 H = 8.4% per each primary H

Ratio of reactivity per hydrogen at C1 : C2 : C3 : C4 = 1 : 2.9: 5.7 : 2.2

D. Conclusions

The mixture of isomeric dichlorobutanes contained 7.8% 1,1-dichlorobutane, 22.7% 1,2 dichlorobutane, 44.4% 1,3-dichlorobutane, and 25.1% 1,4-dicholorobutane. From this data, it was determined that the relative reactivities of the hydrogens found at C1, C2, C3, and C4 was 1 : 2.9 : 5.7 : 2.2. This seems to confirm that secondary hydrogens are more reactive than primary hydrogens. It also showed that the secondary hydrogens at C3, which were further away from the original chlorine found at C1, were more reactive then the hydrogens found at C2. The primary hydrogens found at C4 were more reactive than the primary hydrogens found at C1, which also suggests that the original chlorine at C1 lessened reactivity of the hydrogens near it.

Compared to the given ratio of 5.0 : 3.8 : 1.0 for the reactivity of tertiary to secondary to primary hydrogens of normal alkanes, the expected reactivity of the hydrogens on C1, C2, C3, and C4 of n-butane would be 3(1.0) : 2(3.8) : 2.(3.8) : 3(1.0), which simplifies to 1.0 : 2.5 : 2.5 : 1.0. Compared to the findings in the lab, the found ratio again hints that the original chlorine at C1 made the other primary hydrogens found at C1 and any hydrogens adjacent to it less reactive than expected.

I. Pre-Lab Report

A. Introduction

The purpose of this experiment is to analyze the products of the dehydration of 2-methylcyclohexanol using gas chromatography. Dehydration of the 2-methylcyclohexanol will take place via distillation with sulfuric acid on a microscale level to yield 1-methylcyclohexene and 3-methylcyclohexene. The proportions of these two products will then be determined by analyzing the graphs produced by a gas chromatograph.

B. Main Reaction

2-methylcyclohexanol + H₂SO₄ = 1-methylcyclohexene + 3-methylcyclohexene + H₃O⁺

C. Mechanism

The reaction took place via an E1 mechanism. Refer to the attached sheet.

D. Side Reactions

There were no side reactions.

E. Table of Reactants and Product(s)

II. Post-Lab Report

A. Experimental Procedure

The experimental procedure was followed pretty much as written. The fractionating column was not wrapped with aluminum foil and it was not needed to add additional water to the round bottom flask during heating. The dehydrated 2-methylcyclohexanol solution was not centrifuged after being washed and then dried with calcium chloride. It was allowed to stand for a few minutes instead.

B. Observed Yield and Observed Melting Point or Boiling Point of Product(s)

Area of Peak A = 25

Area of Peak B = 112.5

Percentage of Product A: 18.2%

Percentage of Product B: 81.8%

C. Calucations

Percentage of Product A = (Area of Peak A) / (Area of Peak A + Area of Peak B)

Percentage of Product B = (Area of Peak B) / (Area of Peak A + Area of Peak B)

D. Conclusions

In analysis of the graph produced by the graph chromatograph, the ratio of the two products produced was about 4 to 1. The product with the higher yield should theoretically be 1-methylcyclohexanol. This is because the double bond in 1-methylcyclohexanol is trisubstituted, which is favored over disubstituted and monosubstitued double bonds according to Zaitsev’s rule. The product with the lower yield should be 3-methylcyclohexanol. The double bond in 3-methylcyclohexanol is only disubstituted, which is less favored. There were a few very small peaks on the graph which may be negligible. However, I think one of them could possibly be representative of methylenecyclohexane, which is the third product formed from the dehydration of 2-methylcyclohexanol. This proportion of this product would be minute and it is usually not observed, so this would be highly unlikely.