melting point 14... introduction objective procedure
Posted: Mon May 16, 2022 1:38 pm
melting point 14...
introduction
objective
procedure
QUESTIONS 1. Why is methyl nitrobenzoale formed in this reaction indicad of the anho or para isome! 2. Why does the amount of the dinitration increase at high temperatures? 3. Interpret the inftared spectrum of methyl m niobenzoate, 4. Indicate the product formed on nitration of each of the following compounds: benzene, toluene, chloro benzene, and benzoic acid Experiment 32 p-Nitroaniline eeting Bup Electrophilic Aromatic Substitution Hydrolysis of an Amide Protective Groups Crystallization Thin-Layer Chromatography In this experiment, we convert acetanilide to p-nitroaniline. The sequence of reactions, beginning with aniline, is as shown. The conversion of aniline to acetanilide, the first step, was performed in Experiment 2. NH, och NH-E-CH, CH,- , + CH,COOH Xplain Anline Acetanillde ing reathe O in objected NIECH сн, 4,50. + HNO, Ich NH-CCH, + ortho isomer + H2O ON Nitroacelantide pructing Nary gor ME NHẠC CHỊ NH, + CH,COOH ON + HOW ON Acid Nitrooniline The mechanism for the nitration is essentially identical to that given for the nitration in Experiment 31 The nitronium ion is directed to the positions ortho and para to the acetamido (-NHCOCH,) group This occurs because the resonance electron
Experiment 32. p-Nitrooniline 237 aminlil but why we we not using using the acetamido group releasing effect of that group increases the electron density at those positions, helping to stabilize the intermediates that are formed. Substitution para to the acetamido group is favored over substitution ortho to that group, because the great bulk of the acetamido group shields the ortho positions from approach by reagents. This steric hindrance makes ortho substitution much less likely than para substitution, in which the bulk of the acetamido group has no influence. The ortho substitution product is formed in small quantities in this reaction, but we shall not try to isolate and purify it. If one wished to convert aniline to p-nitroaniline, it seems reasonable, at first glance, to carry out the nitration directly on aniline, without passing through the amide intermediates. The amino group, due to its strong resonance electron-releasing effect. would theoretically direct substitution to the positions ortho and para to itself. In the usual reaction, the free amino group would also activate the benzene ring so greatly toward electrophilic aromatic substitution that substitution would occur at all three ortho and para positions. It would be difficult to get the monosubstituted aniline from this type of reaction. In the nitration of aniline there is the possibility that products with two or three nitro groups would be formed. Since most electrophilic aromatic substitu- bon reactions occur in acidic media, however, the basic amino group is converted to the cationic ammonium group (--NH,). This latter group is electron withdrawing, meta-directing, and deactivating toward further substitution. Since a large proportion of the aniline molecules in acidic solution are protonated, there is a slow formation of \the meta-substituted aniline, along with some ortho and para substitution These com peting reactions are illustrated for nitration: NO, NH, (minor product) NO, why Amino que NH NO: ON NH, NH, NO, (major produt) NO, In the nitration of anilines, there is the additional complication that th aniline are susceptible to oxidation. This oxidation caused by the nitric acid, which is a powerful oxidizing agent, further reduces the yields of desired products in this reaction You can see that it is very difficult to get reasonable yield of p-nitroaniline from the corect nitration of aniline for this reason, the aminor up will converted intially to the accomido group with acetic anhydride. The ac tl grup which is thus attached to the amino group serves as a protective group. The acetyl group reduces the reactivity of the amino group with acids, since the nitrogen, now part of an amide, is 10 longu basic
238 The Experiments Protecting the Amme into quam fram AC Altem.do grup The acetyl group also protects the amino function against oxidation The acetyl group also reduces the electron-releasing resonance of the amino group. As a result, the substituent no longer activates the benzene ning toward multiple substitution as trongly as it did before the acetyl group was attached. Monosubstitution is now possible, so products with only one nitro group can now be isolated from the reaction mixture A protective group must fulfill three important requirements. First, it must be easily attachable to the molecule. The reaction to install the protective group must proceed in high yield, in order not to waste starting material, and it must not require reaction conditions that would cause decomposition of the molecule being protected Second, the protective group must be stable under the conditions of the teacnon in which it is expected to function protectively. Obviously, if the protective group were to come off the molecule during a reaction, it would no longer be able to protect the functional group of interest. Third, the protective group must be one that can be to moved easily once it has fulfilled its protective function. This last requirement is very important. If one wished to restore the original functional group at the end of a reaction sequence, a protective group that could not be removed would not fulfill its role satis factorily. In this experiment, the acetyl group is an example of a useful protective group. The original acetylation of the amino group proceeds in high yield and under mild reaction conditions. The acetyl group is stable under the nitration conditions Finally, it can be removed easily by hydrolysis to regenerate the original amino group SPECIAL INSTRUCTIONS Before you do this experiment, you should read the introductory material in Experi- ments 2 and 31 and also Techniques 3 and 11. Concentrated salfuric and nitric acids, in combination, form a very hazardous and corrosive mixture. These acids should be poured together carefully, and this procedure should be carried out in a hood, since noxious vapors are produced. At the option of the instructor, you may begin with either a sample of acetanilide obtained from the stockroom or the sample of acetanilide you prepared in Experiment 2. If the acetanilide is obtained from Experiment 2. be certain that it has been thoroughly dried before you weigh it. CAUTION: The nitroonilines (ortho, melo, and paro) are all toxic. They are absorbed readily through the skin. Avoid contact with skin, eyes, and clothing. Wash all contact areas with large quantities of water. SML 3:09 Shite Powder LICE Reword 02 ya PROCEDURE Place 30 g of acetanilde in a 125-ml Erlenmeyer flask. Add slowly about 5 mL of concentrated sullunc acid to the acetanilide, Dissolve most of the sold by swiring and luss Ice Ban Nam auror in a going to make oul anilie goingto add sulfure acid and gwr
14 Experiment 32. p-Nitroonline 239 Surring the mixture. Do not be concerned if a small amount of undissolved solid remains It will dissolve in later stages of this procedure. Place the flask in an ice bath. Place 1.8 ml. of concentrated nitric acid another small flask and add about 5 ml of concen trated sulfuric acid to it. CAUTION: This is a hazardous mixture. This mixing should be done carefully in a heo Mix the aclds thoroughly. Tim addsloup By Dames SCOUT you a he te AVA Black Dekksing a Add acid intre Slowly Beense it is Pularing a lot of heat. ndbe roro • Risk Shere Flank Using a disposable capillary pipet, add the mixed acids dropwise to the cooled up sulfuric acid solution of acetanilide. After each addition of acids, swirl the mixture thor- oughly in the ice bath Do not allow the flask to become warm to the touch. Alter 20 nonce 25 mL of an ice-water mixture to the reaction mixture. A suspension of nitroacetanilide Acids isomers will result. Allow this mixture to stand for 5 minutes, with occasional stirring mixed To hydrolyze the nitroacetanilides to the corresponding nitroanilines, heat the material in the flask, using the dilute sulluric acid already present in the flask as the hydrolyzing medium. Add a boiling stone to the Erlenmeyer flask and heat the flask pr a microburner. A wire gauze will disperse the burner flame. ICEB- NOTE TO THE INSTRUCTOR: Many types of bolling stones will dissolve in the acld medium. 14 Heat the mixture gently until the solids dissolve, but do not overheat the mixture be- cause the product may decompose. The solution may darken somewhat during this add heating period. Cool the flask in an ice bath, and when it is cool, add 30 mL of concen- BASE trated aqueous ammonium hydroxide, in five or six portions, to the material in the flask. This addition must be conducted in a hood because noxious fumes, are evolved during ICE the addition. Swirl the flask in the ice bath after each portion of ammonium hydroxide is added. The nitroaniline isomers will precipitale during this addition the ne 44 Pneuleer Collect the precipitated nitroanilines on a Buchner funnel by vacuum filtration Wash the solid thoroughly with small portions of water (total of about 50 mL) While continuing the vacuum, allow the solid to air-dry on the Buchner funnel for several minules. Scrape the solid material from the filter paper into a 50 mL Erlenmeyer flask and add enough hol ethanol to dissolve the solid when the ethanol is boiling, Use the steam tly on bath to hear the solution. When enough ethanol has been added to just dissolve the solid while the ethanol is bolling, allow the solution to cool. When the first crystals appear, place the task in an ice bath to complete the crystallization. Filter the crystals of 7-o-nitroaniline by vacuum filtration, using a Büchner lunnel and a small filter Mask Save dhe filtrate for a later tlc analysis. Wash the crystals with a minimum amount of cold ethanol and allow them to dry by drawing air through them on the filter for a few minutes. Save and dry a small sample of the crystals for a later determination of the melting point and a tic analysis arde Dissolve the remaining crude p nitroaniline in ethanol, using 15 mL of ethanol for rechten of p-nitroaniline. Warm the solution to dissolve the solid Add about 05 gol Ictivater charcoal to the solution and swirl it for a lew minutes. Filter the charcoal from the wit Heat hamol -PH case it mes Cha -18,
the solution by gravity, using a fluted filter paper. It probably will be necessary to repeat this gravity filtration. Concentrate the filtrate to about one third of its original volume on the steam bath or hot plate. Allow the solution to cool. When the first crystals appear. place the llask in an ice bath. After crystallization is complete, collect the crystals on a Büchner funnel by vacuum filtration. Allow the crystals to air dry on the Buchner funnel by continuing to draw a vacuum on them When the crystals are dry, weigh them. Determine the melting points of the two samples of crystals obtained before and after this final crystallization (literature mp 149 °C). Save a small sample of this yellow purified p-nitroaniline for tic analysis. A labeled vial of the product should be submit- ted to the instructor. For the thin layer chromatographic analysis, the three samples (fitrate from first crystalization, crude p-nitroaniline, and purified product) are each dissolved in a few drops of ethanol. Each sample is spotted on a single tic plate that has been prepared from a microscope slide using silica gel G (Technique 11, Sections 11 2A, 113, and 11.4, pp. 617-623). Using methylene chloride as the solvent, develop the plate and compare the pattern of spots obtained for each sample. The materials being studied are colored, so they should be visible. However, it may be necessary to intensity the colors of the spots by briefly exposing the tic plate to iodine vapors (Technique 11, Section 11.6, p. 623) The report should contain the melting points of the two samples of p-nitroaniline and a discussion of the differences observed in melting-point behavior. The percentage yield should also be reported. The report should also include a discussion of the le results obtained with the three samples analyzed, with particular emphasis on the differ- ences between the pattern of spots for each sample QUESTIONS 1. Explain why the acetamido group is an ortho para directing group. Why should it be less effective jo activating the aromatic ring toward further substitution than an amuno group? 2. Outline the mechanism of the acid catalyzed hydrolysis of p natroacetanilide to yield p nitraaniline 3. o Nitroaniline is more soluble in ethanol than p nitroanline. Propose a scheme by which a pure sample of o nitroaniline might be obtained from this reaction 4. Explain how you could use column chromatography to separate o-astroanlıne from the filtrate What adsorbent and solvent or solvents would you use? Which compound would elute first 5. N Methylbenzamide, an isomer of acetanilide when allowed to react with HNO, H SO. gives a differ ent product from what is obtained from acetanilide What is the structure of the mon nitrated product? Why is it produced? 'If continued prblems existen removing the decolonizing carbon, use Filter Aid (Technique 2. Section 24 p 520 Commercially prepared plates, such as those described in Experiment 4. may also be used Although methylene chloride gives an adequate separation in the a better separation is obtained with a stw methylene chloride pentan mixtur
introduction
objective
procedure
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Experiment 32. p-Nitrooniline 237 aminlil but why we we not using using the acetamido group releasing effect of that group increases the electron density at those positions, helping to stabilize the intermediates that are formed. Substitution para to the acetamido group is favored over substitution ortho to that group, because the great bulk of the acetamido group shields the ortho positions from approach by reagents. This steric hindrance makes ortho substitution much less likely than para substitution, in which the bulk of the acetamido group has no influence. The ortho substitution product is formed in small quantities in this reaction, but we shall not try to isolate and purify it. If one wished to convert aniline to p-nitroaniline, it seems reasonable, at first glance, to carry out the nitration directly on aniline, without passing through the amide intermediates. The amino group, due to its strong resonance electron-releasing effect. would theoretically direct substitution to the positions ortho and para to itself. In the usual reaction, the free amino group would also activate the benzene ring so greatly toward electrophilic aromatic substitution that substitution would occur at all three ortho and para positions. It would be difficult to get the monosubstituted aniline from this type of reaction. In the nitration of aniline there is the possibility that products with two or three nitro groups would be formed. Since most electrophilic aromatic substitu- bon reactions occur in acidic media, however, the basic amino group is converted to the cationic ammonium group (--NH,). This latter group is electron withdrawing, meta-directing, and deactivating toward further substitution. Since a large proportion of the aniline molecules in acidic solution are protonated, there is a slow formation of \the meta-substituted aniline, along with some ortho and para substitution These com peting reactions are illustrated for nitration: NO, NH, (minor product) NO, why Amino que NH NO: ON NH, NH, NO, (major produt) NO, In the nitration of anilines, there is the additional complication that th aniline are susceptible to oxidation. This oxidation caused by the nitric acid, which is a powerful oxidizing agent, further reduces the yields of desired products in this reaction You can see that it is very difficult to get reasonable yield of p-nitroaniline from the corect nitration of aniline for this reason, the aminor up will converted intially to the accomido group with acetic anhydride. The ac tl grup which is thus attached to the amino group serves as a protective group. The acetyl group reduces the reactivity of the amino group with acids, since the nitrogen, now part of an amide, is 10 longu basic
238 The Experiments Protecting the Amme into quam fram AC Altem.do grup The acetyl group also protects the amino function against oxidation The acetyl group also reduces the electron-releasing resonance of the amino group. As a result, the substituent no longer activates the benzene ning toward multiple substitution as trongly as it did before the acetyl group was attached. Monosubstitution is now possible, so products with only one nitro group can now be isolated from the reaction mixture A protective group must fulfill three important requirements. First, it must be easily attachable to the molecule. The reaction to install the protective group must proceed in high yield, in order not to waste starting material, and it must not require reaction conditions that would cause decomposition of the molecule being protected Second, the protective group must be stable under the conditions of the teacnon in which it is expected to function protectively. Obviously, if the protective group were to come off the molecule during a reaction, it would no longer be able to protect the functional group of interest. Third, the protective group must be one that can be to moved easily once it has fulfilled its protective function. This last requirement is very important. If one wished to restore the original functional group at the end of a reaction sequence, a protective group that could not be removed would not fulfill its role satis factorily. In this experiment, the acetyl group is an example of a useful protective group. The original acetylation of the amino group proceeds in high yield and under mild reaction conditions. The acetyl group is stable under the nitration conditions Finally, it can be removed easily by hydrolysis to regenerate the original amino group SPECIAL INSTRUCTIONS Before you do this experiment, you should read the introductory material in Experi- ments 2 and 31 and also Techniques 3 and 11. Concentrated salfuric and nitric acids, in combination, form a very hazardous and corrosive mixture. These acids should be poured together carefully, and this procedure should be carried out in a hood, since noxious vapors are produced. At the option of the instructor, you may begin with either a sample of acetanilide obtained from the stockroom or the sample of acetanilide you prepared in Experiment 2. If the acetanilide is obtained from Experiment 2. be certain that it has been thoroughly dried before you weigh it. CAUTION: The nitroonilines (ortho, melo, and paro) are all toxic. They are absorbed readily through the skin. Avoid contact with skin, eyes, and clothing. Wash all contact areas with large quantities of water. SML 3:09 Shite Powder LICE Reword 02 ya PROCEDURE Place 30 g of acetanilde in a 125-ml Erlenmeyer flask. Add slowly about 5 mL of concentrated sullunc acid to the acetanilide, Dissolve most of the sold by swiring and luss Ice Ban Nam auror in a going to make oul anilie goingto add sulfure acid and gwr
14 Experiment 32. p-Nitroonline 239 Surring the mixture. Do not be concerned if a small amount of undissolved solid remains It will dissolve in later stages of this procedure. Place the flask in an ice bath. Place 1.8 ml. of concentrated nitric acid another small flask and add about 5 ml of concen trated sulfuric acid to it. CAUTION: This is a hazardous mixture. This mixing should be done carefully in a heo Mix the aclds thoroughly. Tim addsloup By Dames SCOUT you a he te AVA Black Dekksing a Add acid intre Slowly Beense it is Pularing a lot of heat. ndbe roro • Risk Shere Flank Using a disposable capillary pipet, add the mixed acids dropwise to the cooled up sulfuric acid solution of acetanilide. After each addition of acids, swirl the mixture thor- oughly in the ice bath Do not allow the flask to become warm to the touch. Alter 20 nonce 25 mL of an ice-water mixture to the reaction mixture. A suspension of nitroacetanilide Acids isomers will result. Allow this mixture to stand for 5 minutes, with occasional stirring mixed To hydrolyze the nitroacetanilides to the corresponding nitroanilines, heat the material in the flask, using the dilute sulluric acid already present in the flask as the hydrolyzing medium. Add a boiling stone to the Erlenmeyer flask and heat the flask pr a microburner. A wire gauze will disperse the burner flame. ICEB- NOTE TO THE INSTRUCTOR: Many types of bolling stones will dissolve in the acld medium. 14 Heat the mixture gently until the solids dissolve, but do not overheat the mixture be- cause the product may decompose. The solution may darken somewhat during this add heating period. Cool the flask in an ice bath, and when it is cool, add 30 mL of concen- BASE trated aqueous ammonium hydroxide, in five or six portions, to the material in the flask. This addition must be conducted in a hood because noxious fumes, are evolved during ICE the addition. Swirl the flask in the ice bath after each portion of ammonium hydroxide is added. The nitroaniline isomers will precipitale during this addition the ne 44 Pneuleer Collect the precipitated nitroanilines on a Buchner funnel by vacuum filtration Wash the solid thoroughly with small portions of water (total of about 50 mL) While continuing the vacuum, allow the solid to air-dry on the Buchner funnel for several minules. Scrape the solid material from the filter paper into a 50 mL Erlenmeyer flask and add enough hol ethanol to dissolve the solid when the ethanol is boiling, Use the steam tly on bath to hear the solution. When enough ethanol has been added to just dissolve the solid while the ethanol is bolling, allow the solution to cool. When the first crystals appear, place the task in an ice bath to complete the crystallization. Filter the crystals of 7-o-nitroaniline by vacuum filtration, using a Büchner lunnel and a small filter Mask Save dhe filtrate for a later tlc analysis. Wash the crystals with a minimum amount of cold ethanol and allow them to dry by drawing air through them on the filter for a few minutes. Save and dry a small sample of the crystals for a later determination of the melting point and a tic analysis arde Dissolve the remaining crude p nitroaniline in ethanol, using 15 mL of ethanol for rechten of p-nitroaniline. Warm the solution to dissolve the solid Add about 05 gol Ictivater charcoal to the solution and swirl it for a lew minutes. Filter the charcoal from the wit Heat hamol -PH case it mes Cha -18,
the solution by gravity, using a fluted filter paper. It probably will be necessary to repeat this gravity filtration. Concentrate the filtrate to about one third of its original volume on the steam bath or hot plate. Allow the solution to cool. When the first crystals appear. place the llask in an ice bath. After crystallization is complete, collect the crystals on a Büchner funnel by vacuum filtration. Allow the crystals to air dry on the Buchner funnel by continuing to draw a vacuum on them When the crystals are dry, weigh them. Determine the melting points of the two samples of crystals obtained before and after this final crystallization (literature mp 149 °C). Save a small sample of this yellow purified p-nitroaniline for tic analysis. A labeled vial of the product should be submit- ted to the instructor. For the thin layer chromatographic analysis, the three samples (fitrate from first crystalization, crude p-nitroaniline, and purified product) are each dissolved in a few drops of ethanol. Each sample is spotted on a single tic plate that has been prepared from a microscope slide using silica gel G (Technique 11, Sections 11 2A, 113, and 11.4, pp. 617-623). Using methylene chloride as the solvent, develop the plate and compare the pattern of spots obtained for each sample. The materials being studied are colored, so they should be visible. However, it may be necessary to intensity the colors of the spots by briefly exposing the tic plate to iodine vapors (Technique 11, Section 11.6, p. 623) The report should contain the melting points of the two samples of p-nitroaniline and a discussion of the differences observed in melting-point behavior. The percentage yield should also be reported. The report should also include a discussion of the le results obtained with the three samples analyzed, with particular emphasis on the differ- ences between the pattern of spots for each sample QUESTIONS 1. Explain why the acetamido group is an ortho para directing group. Why should it be less effective jo activating the aromatic ring toward further substitution than an amuno group? 2. Outline the mechanism of the acid catalyzed hydrolysis of p natroacetanilide to yield p nitraaniline 3. o Nitroaniline is more soluble in ethanol than p nitroanline. Propose a scheme by which a pure sample of o nitroaniline might be obtained from this reaction 4. Explain how you could use column chromatography to separate o-astroanlıne from the filtrate What adsorbent and solvent or solvents would you use? Which compound would elute first 5. N Methylbenzamide, an isomer of acetanilide when allowed to react with HNO, H SO. gives a differ ent product from what is obtained from acetanilide What is the structure of the mon nitrated product? Why is it produced? 'If continued prblems existen removing the decolonizing carbon, use Filter Aid (Technique 2. Section 24 p 520 Commercially prepared plates, such as those described in Experiment 4. may also be used Although methylene chloride gives an adequate separation in the a better separation is obtained with a stw methylene chloride pentan mixtur