Archives for April 2008

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.

The movie “As Good as It Gets” portrays a character, Melvin Udall, who suffers from obsessive-compulsive disorder. Obsessive-compulsive disorder falls under the category of anxiety disorders, which contains a group of disorders that share similar characteristics. Anxiety disorders all typically become aroused over apprehension over an anticipated problem. There are physical, cognitive, and emotional symptoms which are elicited from the apprehension. Physical symptoms may include increased heart rate, increased respiration, sweating, and trembling. Cognitive symptoms may include preoccupation, a loss of concentration, and rumination. Finally, emotional symptoms may include apprehensiveness and terror. These symptoms result from the “flight or fight” response triggered in our body. This response comes from the autonomic nervous system and specifically the parasympathetic nervous system. These are parts of the nervous system which control things we do not think about, like breathing and keeping our heart beating. It is not necessarily bad for the parasympathetic nervous system to become aroused because it help in times of danger, but in the case of someone who suffers from an anxiety disorder, it becomes aroused too easily or too often. Irrational cognitions lead to its arousal.

In the case of someone with obsessive-compulsive disorder, the subject will typically have intrusive and unwilling thoughts (obsessions) which give rise to anxiety. Because of this created anxiety, the subject will feel compelled to perform a behavior related to the obsession. These behaviors (compulsions) become ritualized to a point where they are detrimental to the subject’s functioning because the compulsions are repeated with a high frequency. Examples of obsessions include fear of contamination, aggressive impulses, extreme doubt, and extreme indecision. Examples of compulsions include repeatedly washing one’s hands, checking locks over and over, and pursuing cleanliness and orderliness through elaborate routines. Obsessive-compulsive disorder is a chronic disorder and it is difficult to completely recover from it. It often develops in the subject before age 10 or late in adolescence.

The treatment used to cure obsessive-compulsive disorder, like many anxiety disorders, is through exposure. However, unlike the exposure for most other anxiety disorders which is gradual, the exposure for obsessive-compulsive disorder must be intense. The subject is to be exposed to one of their obsessions, but not be allowed to perform the compulsion associated with the obsession. They can not perform the compulsion at all. For example, if they subject has a fear of contamination and washes their hands multiple times, the treatment would be to make them touch something dirty and not allow them to wash their hands. If you let them wash their hands even once or twice, the treatment would not be effective. Through time their anxiety will extinguish and they will no longer have the obsessions, and in turn, the compulsions.

The movie “As Good as It Gets” is about how the main character, Melvin Udall, is first portrayed as an arrogant, insensitive person who suffers from obsessive-compulsive disorder and by the end, he becomes a more caring person and suffers slightly less from obsessive-compulsive disorder than he does at the beginning of the movie. Melvin is neighbors with an artist named Simon who is robbed and mugged, and goes through some emotional problems. Melvin reluctantly helps him out by watching his dog and by eventually letting Simon move in with him. Carol is a waitress at a diner where Melvin goes for breakfast every day. Eating breakfast at the diner and having Carol serve him is part of Melvin’s routine and when she takes off work one day to take care of her sick son, Melvin becomes very anxious because his routine is interrupted. At this point he starts to become involved with Carol’s life and eventually by the end of the movie they are dating. During the course of the movie, Melvin portrays many obsessions and compulsions.

One obsession that Melvin suffers from is a fear of contamination. Melvin first shows this obsession through the compulsion of cleaning himself. He uses steaming hot water and a brand new bar of soap when washing his hands. He uses the bar of soap for only a few seconds, throws it away, and then opens a new bar of soap to use. When taking showers, Melvin again uses steaming hot water and stays in the shower for much longer than the normal person would. Another way Melvin shows his fear of contamination is by always wearing gloves when he outside of his apartment. He is afraid to touch anything with his bare hands when he does not know that it is clean. He also throws the gloves away after wearing them because he thinks they have been contaminated. Melvin shows extreme anxiety when people try to touch him. The thought of being touched by another person and becoming contaminated controls him, and he makes a very conscious effort to avoid being touched. Lastly, Melvin always brings his own plastic utensils to use at the diner instead of the utensils provided. He thinks that the utensils provided at the diner are not clean, even though everyone else at the diner uses them. This again shows his obsession over contamination.

Another obsession Melvin has is about organization and control. His apartment is portrayed as being very organized and that he made a conscious effort and took time to organize it. For example, he has jars filled with hundreds of “Skittles” or “M&M’s that are separated by their color. Melvin’s day must also be standardized and routine. He goes to the same diner every day for breakfast and has the same waitress wait on him, which in turn gives him a sense of control. When the waitress is not there to serve him one day, he becomes very anxious because her absence ruins his organized and routine based day. Also, when Melvin is asked to take Simon to visit his parents in Baltimore, Melvin is very reluctant to take Simon partially because he does not want his routine to be interrupted. Melvin is a writer, so he could easily take a couple days off for the trip, but the thought of breaking his routine troubles him.

One last obsession Melvin shows is that of doubt. Melvin has a compulsion of locking the door to his apartment several times, just to make sure it is locked. When Melvin and Carol are going out for dinner, Melvin asks several people if the restaurant serves hard shell crabs. Everyone he asks replies “yes”, but because of his obsession about doubt, he asks multiple people. If he were to only lock the doors once or only ask one person if the restaurant carried hard shell crabs, he would become anxious because his obsession of doubt.

Melvin shows a few other compulsions during the movie which do not seem to have blatant corresponding obsessions. For example, it is stated that Melvin has written 62 books. That is an extreme number of books for anybody to write. The high number of books Melvin has written may be due in part to his obsession about routine and organization. It is not clearly shown in the movie, but part of Melvin’s routine may be to write for so many hours of each day or to write a certain number of pages each day. One other compulsion Melvin shows is that he does not step on cracks. Whether he is walking on a tile floor, a brick pathway, or on the sidewalk, he will make a very conscious effort not to step on any cracks. One way to explain this might be through his obsession about doubt. Something bad may have happened to him in the past when he stepped on a crack, so now he has a recurring thought that something bad will happen to him again if he were to step on a crack. He could have an obsession of doubt about his safety.

The symptoms portrayed in the movie seem very accurate for someone with obsessive-compulsive disorder; however the means through which Melvin’s symptoms are diminished do not match the normal treatment for someone with the disorder. The main way to treat the disorder is through intense exposure to the obsessions without letting the subject perform the compulsions associated with the obsessions. However, in the movie Melvin mentions that his doctor prescribed him medication to deal with his disorder. Medication is not the typical means to treating obsessive-compulsive disorder. Melvin also mentions that his doctor told him he should break his routine. This would be a more correct way for Melvin to overcome his disorder, but it does not sound like his psychologist gave him specific instructions. In my opinion, it seems like Melvin was given the discrepancy to determine when he wants to break his routine and the extent to which he would deviate from the norm. This would not be good judgment in part by the psychologist. They should have probably exposed Melvin to some of his obsessions during therapy and not let him perform the compulsion.

Also in the movie, it is suggested that as Melvin becomes connected to Carol the waitress his symptoms start to diminish. For example, near the end of the movie, Melvin is preoccupied with thoughts about Carol and he forgets to lock his door. Someone with obsessive-compulsive disorder would most likely not forget to perform their ritual of locking their door just because they are thinking about something else. Usually the obsessions are so engraved into their minds that they will stop to perform the compulsions no matter what. His fear of contamination also diminishes to an extent when he is with Carol, as he allows her to kiss him. This exposure seems like a more clinical approach to extinguishing his fear of contamination. It is a sudden and intense exposure to possible contamination. Melvin can not just go and brush his teeth after kissing her because that would be rude and he likes her, so he starts to see his fear of contamination may be irrational and he starts to become more physical. This is shown when he pats Simon on the shoulder later on, which is something he never would have done at the beginning.

Lastly, at the very end of the movie Melvin finally walks on cracks when he is with Carol. He is forced to walk on the cracks because he would look silly walking 10 feet away from her where there are no cracks. It is a sudden and intense exposure to walking on cracks, and Melvin sees that nothing bad happens, so his obsession of doubt may start to diminish. Overall, the movie “As Good as It Gets” does a fairly good job at portraying obsessive-compulsive disorder, however it tries to portray the way it is diminished is through personal connection, rather than through intense exposure to obsessions without the ability to perform the associated compulsions.