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This 32 page Study Guide was uploaded by Moises Trevino on Friday February 26, 2016. The Study Guide belongs to 2325 at University of Texas at Dallas taught by Claudia Taenzler in Spring 2016. Since its upload, it has received 103 views. For similar materials see Introductory Organic Chemistry II in Chemistry at University of Texas at Dallas.
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Date Created: 02/26/16
Chapter 20 & 21 Reaction Chart – Carboxylic acids and derivatives -Chapter 20 and 21 deals with reaction/synthesis of carboxylic acids and its derivatives. There are essentially 5 different derivatives of carboxylic acid: Acid Chlorides, Anhydrides, Esters, Amides, and Nitriles. Essentially, the majority of the reactions covered in this chapter are interconverting into the different derivative forms, with the rest of the reactions mostly review from previous chapters. Again, there are 2 general mechanisms for a Carboxylic acid/derivate reaction: The Acid catalyzed mechanism, and the Basic Catalyzed mechanism, which are both shown below. -The Basic catalyzed mechanism is primarily utilized for Acid Chlorides and Anhydrides. Since the substituent attached to the acyl group (Cl or carboxylate ion) are good leaving groups, it makes the Acid Chloride and Anhydride good electrophiles so that the nucleophile can directly attack the carbonyl carbon without having to protonatethe oxygen to make it more electrophilic. In this reaction, an acid chloride is reacting with an alcohol. Once it attacks, a tetrahedral intermediate will form, with an alkoxide, chloride, an alcohol as substituents on the carbonyl carbon. Now, at this point, the moststable leaving group will be kicked off. In this case, Chloride is the most stable leaving group, so it will leave, with the oxygen reforming the carbonyl group. Chloride will then extract a hydrogen, and an ester will form. -In the acid catalyzed mechanism, the main difference is that the carbonyl oxygen is first protonated to make ita better electrophile. Therefore this mechanism typically occurs for Esters, Amides, and Carboxylic acids, which are less reactive than Acid Chlorides and Anhydrides. Once the oxygen is protonated, the nucleophile will attack, and a tetrahedral compound will form. In this case, the OH will be protonated to form water, and will be kicked off. The oxygen will reform the carbonyl again, and a hydrogen will be extracted to form the ester. -Below is a diagram from the book that shows the reactivity of the carboxylic acid derivatives. The reactivity of the carboxylic acid/derivate is dictated by the substituent attached on the acyl group. The more stable the leaving group is on the carboxylic acid derivative, the faster the reaction will occur in a nucleophilic substitution reaction. The leaving group of an acid chloride is a chloride ion, which is a very weak base, and is very stable by itself. Therefore, it will readily be kicked off, and will be the most reactive carboxylic acid derivative. Essentially, carboxylic acid derivates can ONLY react to form less reactive derivatives. Therefore, though an Acid Chloride can directly convert to an amide, an Amide can’t be directly converted into an acid chloride since the amine ion is much more reactive than a chloride ion. Know this reactivity chart really well! You may be asked to rankcarboxylic acid derivatives by their reactivity, which is dictated by the stability of their leaving group! It is also very important to consider when approaching reaction questions! Below I have drawn a general flowchart of the conversion of the various forms. This is probably the most important aspect of Chapter 20 & 21, so know which derivatives can be converted to which another form and the reagents needed to perform the reaction! Basically, if you want to form an acid chloride, use SOCl . I2 you want to form an anhydride, add a carboxylic acid. If you want to form an ester, add an alcohol. If you want to form an amide, add an amine, and if you want to reform a carboxylic acid, add water and H+. -There are many review reactions from previous Chapters that are on this chart. You should already have a good understanding of those reactions, so I will try to emphasize the new reactions you should know. Synthesis of Carboxylic acids Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Oxidation of -From Chapter 11, a primary alcohol can be oxidized with a chromium reagent, which will first Reactant– Primary Alcohol - Won’t be directly asked Primary oxidize the alcohol to an aldehyde. However, since chromium is a strong oxidizing agent, it will or aldehydes this, but know this reaction alcohols/alde continue to oxidize the aldehyde into a carboxylic acid. Reagent: A Chromium (VI) because it is useful for -hydes reagent – Cr(VI) (Na2Cr 2 7 synthesis questions! (Ch 11) or CrO3in H 2O )4 or KMnO 4 Product – A carboxylic acid Oxidative -From O.Chem 1, an Alkene can react with warm, acidic, and concentrated KMnO to form 4 Reactant- An Alkene - Shouldn’t be asked this, Cleavage of ketones/aldehydes. Any aldehydes present will oxidize further to carboxylic acids. Reagent – Warm, acidic, or know in case, specifically for Alkenes (Ch concentrated KMnO synthesis questions! 4 8) Product – Mixtures of -Remember, the permangate ketones, or carboxylic acids has to be in warm, concentrated, or acidic conditions to form ketones/carboxylic acids Oxidation of -From O.Chem 1, an alkyne can react with warm, basic, concentrated KMnO to cleave the Reactant An Alkyne - Shouldn’t be asked this, 4 alkynes (Ch 9) triple bond to form carboxylate salts, which can be protonated to form carboxylic acids (terminal or internal) know in case, specifically for Reagent: Warm, basic, synthesis questions! concentrated KMnO or O - Warm,concentrated, and 4 3 and H 2 basic, NOT acidic KMnO is4 Product: Multiple needed to form carboxylic Carboxylic acids acid -An alkyne can also react with ozone and H O t2at will cleave the triple bond to form 2 carboxylic acids as well Oxidation of -Remember from Ch 17 that KMnO or ho4 chromic acid can be used to oxidize carbon groups Reactant- Benzene ring - Won’t be directly asked alkylbenzene on benzene rings to carboxylic acids. Only alkane carbon groups will react, any other group will with carbon (alkane) this, but know this reaction (Ch 17) not be reacted! substituents because it is useful for Reagent – KMnO , N4OH synthesis questions! (basic conditions), or -Will oxidize any adjacent Chromic acid and heat carbon group (alkyl groups, Product – carboxylic acids carbonyl groups, etc…) on benzene rings Carboxylatio Remember from O.Chem 1 that Grignard reagents are very strong nucleophilies. Therefore, a Reactant: A Grignard -Know this reaction! Not n of Grignard Grignard reagent can react with CO ,2and can form a carboxylic acid. reagent (R-MgBr) really a new reaction, but a reagent Reagent: Carbon dioxide good reaction to synthesis (CO2) carboxylic acids with. Product: A carboxylic acid Hydrolysis of -Nitriles (-CN) can be hydrolyzed under acidic conditions. The nitrile will first be hydrated to Reactant: A Nitrile (R-CN) -Know this reaction! It is a Nitriles form an amide, which will be hydrated again to form a carboxylic acid. Note that for the Reagent: H+ and H O2 useful reaction for (Ch 18) reaction, you can just write H+, water is assumed to be present Product: A Carboxylic acid converting cyanides to carboxylic acids Reactions of Carboxylic Acids Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products The Fischer -A carboxylic acid can be reacted with an alcohol. Since the carboxylic acid is not a good Reactant– Carboxylic acid -Know this reaction and the Esterification electrophilie, it will be protonated first to make it more electrophilic. After protonation, the Reagent: An Alcohol in mechanism! It essentially (Ch 11) alcohol will attack, and a tetrahedral intermediate will form acidic conditions follows the acid catalyzed Product – Ester, with the mechanism. alcohol R group attached to -Remember, the carboxylic the O acid has to be reacted in acidic conditions to protonate the oxygen to make it more electrophilic! -One of the alcohols will be protonated, leaving as water, forming an ester with the alcohol attached to the carbonyl carbon. The overall reaction is shown below Esterfication -A carboxylic acid can react with Diazomethane (Diazonium with a methyl attached) to form an Reactant- Carboxylic acid -Don’t need to know the using ester. The negatively charged carbon will first extract the carboxylic acid hydrogen, now forming Reagent – Diazomethane mechanism, but know the Diazomethan a negative charge on the oxygen, which will then attack the methyl group, with N l2aving, (CH 2 2 reaction! e forming the ester. Product – An ester, with -Usually only uses the methyl group attached diazomethane (CH N 3. 2 to the oxygen Direct -Similar to the reaction of the diazomethane, the carboxylic acid hydrogen will first be Reactant: Carboxylic acid -Don’t need to know the synthesis of extracted by the amine, forming the carboxylate ion. Under heated conditions, this will react Reagent: An amine (can be mechanism, but know the Amides (Ch with the amine to form an amide. ammonia, primary or reaction! 19) secondary), and heat -Usually better to convert Product: An Amide, with carboxylic acid to an acid the amine replacing the OH chloride, then form the amide -Though a carboxylic acid can be converted straight to an amide, it is usually preferred to convert the carboxylic acid to an acid chloride, then to the amide since weaker conditions can be used Reduction of -Remember that carboxylic acids can react with LAH to form primary alcohols. The first Reactant- Carboxylic acids - Don’t need to know the Carboxylic addition will actually form an aldehyde, and the second addition will form the primary alcohol. Reagent – LiAlH (LAH) or mechanism, but know the 4 Acids to BH 3THF reaction! alcohols (Ch Product – Primary alcohols -Remember, LiAlH is4 10) reactive, not selective, while BH 3THF is selective for carboxylic acids - BH 3THF can also be used to reduce carboxylic acids to primary alcohols, but will preferentially react with carboxylic acids over any other carbonyl group. Therefore, with only 1 addition, will only reduce the carboxylic acid Synthesis of -Acarbonyl oxygen of the carboxylic acid can react with SOCl to2form a resonance stabilized Reactant: Carboxylic acids -Don’t need to know the Acid compound shown below Reagent: SOCl o2 (COCl) 2 mechanism, but know the Chlorides Product: Acid chlorides reaction! -One of the only reactions to form acid chlorides! They are the most reactive carboxylic acid derivatives, and essentially form every -The chloride will then leave, and the carbonyl on the sulfur will reform, with the chloride single carboxylic acid extracting a hydrogen from the carbonyl oxygen, forming a chlorosulfite anhydride derivative. -SOCl 2an only be reacted on carboxylic acids to form acid chlorides. It will not work with anhydrides, esters, and amides! -Chloride will then attack the anhydride, preferentially the carbon instead of the sulfur. The ester substituent will then be removed, now forming the acid chloride. You don’t need to know the mechanism! -The overall reaction is shown below Reduction of There is no direct way to convert a carboxylic acid into an aldehyde. It must be converted to an Reactant: An acid chloride -Don’t need to know the carboxylic acid chloride first by reacting a carboxylic acid can be reacted with SOCl 2o attach a chlorine (can be generated by mechanism, but know the acids to on the carbonyl carbon. adding a carboxylic acid reaction! aldehydes with a thionyl chloride -LiAlH(O t-Bu)3is a weaker (Ch 18) (SOCl ) reducing agent and can 2 Reagent: Lithium tri-tert- reduce the acid chloride to butoxyaluminum hydride the aldehyde form, while (LiAlH(O t-Bu)3) LiAlH4would reduce it all the The acid chloride can then be reduced by Lithium tri-tert-butoxyaluminum hydride (LiAlH(O-t- Product: An aldehyde, way to an alcohol bu)3). This is a weaker reducing agent than LAH, so will only reduce the acid chloride to the aldehyde and not the alcohol. Notice that this only forms aldehydes, not ketones! Alkylation of From Ch 18, to convert a carboxylic acid into a ketone, 2 additions of a organolithium are Reactant- A carboxylic acid -Don’t need to know the Carboxylic needed(any R group can be used for the organolithium compound). The first organolithium Reagent – 2 organolithium mechanism, but know the Acids to form reagent is used to deprotonate the acidic carboxylic hydrogen to form a carboxylate ion. The compounds (any R group reaction! Keep in mind you ketones (Ch second addition will be used to form a dianion. can be used). Notice that in need 2 organolithium 18) the first deprotonation, a reagents to form the weaker base such as –OH ketone! can be used -One of the only reactions Product – A ketone with that directly converts an another R group attached carboxylic acid to a ketone replacing the OH. Protonation of the dianion will cause a dehydration, and reformation of the carbonyl, now forming a ketone The overall reaction is shown below Reactions involving Acid Chlorides Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Interconvers- -Remember that acid chlorides react under basic catalyzed mechanisms since they are more Reactant– An Acid Chloride - Know this reaction and the ions of Acid reactive than other derivatives. Therefore, nucleophilies can directly attack the carbonyl Reagent: Depends on what mechanism! Chloride to carbon without protonation of the oxygen. Below are different reactions of acid chlorides to derivative is formed -Essentially follows the basic Carboxylic convert to different carboxylic acid derivatives. -Formation of anhydride – catalyzed mechanism, acid -Acid chloride can react with with a carboxylic acid (or carboxylate ion), forming a tetrahedral carboxylic acid or the salt where the nucleophile derivative intermediate, and the loss of chloride, forming an anhydride form attacks first, forms the (anhydride, -Formation of an ester – an tetrahedral intermediate, ester, amide, alcohol and kicks off chloride carboxylic -Formation of an amide – -Remember the reactivity acid) ammonia, primary or chart! Since acid chlorides secondary amine are the most reactive, with – -Formation of a carboxylic Cl being a good leaving acid –water group, it can interconvert to Product – Anhydride, ester, all the different derivatives: -If an Acid chloride reacts with an alcohol, it will follow the same mechanism, with the –Cl amide, or carboxylic acid anhydrides, ester, amide, or leaving, forming an ester carboxylic acid again. -If an Acid chloride reacts with an amine, it will form an amide -Acid chlorides can also react with water (no acidic conditions needed), to reform carboxylic acid. Reduction of Acid chlorides can be reduced by different reagents to form different products, all listed below. Reactant An acid chloride - Don’t need to know the Acid -The acid chloride can then be reduced by Lithium tri-tert-butoxyaluminum hydride (LiAlH(O-t- Reagent: mechanism, but know the Chlorides bu)3). This is a weaker reducing agent than LAH, so will only reduce the acid chloride to the Formation of an aldehyde - reaction! (Ch 10, 18) aldehyde and not the alcohol. Notice that this only forms aldehydes, not ketones! (LiAlH(O t-Bu)3 -The strength of the Formation of an alcohol - reducing agent dictates the LAH product form. A weaker -Formation of a ketone – reducing agent such as the R2CuLi hindered LAH will only form Product: An aldehyde, the aldehyde, while -If LiAl4 is used, it will reduce the acid chloride all the way to a primary alcohol. Remember LAH alcohol,or ketone unhindered LAH will react to adds twice, with the first time forming the aldehyde, and the second forming the alcohol. reduce the acid chloride all the way to an alcohol -To convert an acid chloride into a ketone, A lithium dialkylcuprate (Gilman reagent) is needed to add an R group to the acid chloride. Notice that 2 R groups are attached to the reagent in order for just one to attach onto the carbonyl to form the ketone Grignard -An acid chloride will react with a Grignard reagent 1 time to form a ketone, which will react Reactant: An Acid Chloride -Don’t need to know the reactions of again with the Grignard reagent for form a tertiary alcohol, with 2 additions of the Grignard on Reagent: Grignard reagent mechanism, but know the acid chlorides the carbonyl group. A tertiary alcohol is always formed, with 2 additions of Grignards! (R-MgBr) reaction! (Ch 10) Product: A tertiary alcohol, -A ketone will form with 1 with 2 additions of the equivalent addition, but an Grignard reagent additional equivalent will form the 3 alcohol with 2 additions of grignards Reactions involving Anhydrides Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Formation of -Under acidic conditions, a compound with 2 carboxylic acids in a chain can cyclize. One of the Reactant– A dicarboxylic - Know this reaction and the a cyclic carbonyl oxygens will get protonated, allowing for the opposite carboxylic acid to attack the acid mechanism! You will be anhydride more electrophilic carbon, forming a cyclic tetrahedral shown below. Reagent: Acidic (H+) given several questions that conditions involves the formation of Product – A cyclic cyclic carboxylic acid anhydride (2 carbonyl derivatives! groups adjacent to a cyclic O), which can be reacted -Under acidic conditions, one of the alcohols will get protonated, and leave as water, further to form multiple carboxylic acid derivatives reforming the carbonyl and forming the cyclic anhydride -The cyclic anhydride can react with a nucleophile, breaking the ring and reacting with 1 side of the carboxylic acid, forming unsymmetrical carboxylic acid derivative compounds. Notice that the side that kicks off the most stable leaving group is reacted. The carboxylic acid with the fluorines attached is more stable because it helps to stabilize the excess electron density Interconversi -Like acid chlorides, an anhydride reacts in a basic catalyzed mechanism involved a direct Reactant: Anhydride - Know this reaction and the -on of nucleophilic attack onto the electrophilic carbon, forming the tetrahedral intermediate, and Reagent: mechanism! Anhydrides kicking off the carboxylate ion, forming the new carboxylic acid derivative. -Formation of an ester – an -Essentially follows the basic to other alcohol catalyzed mechanism, carboxylic -Formation of an amide – where the nucleophile acid ammonia, primary or attacks first, forms the derivatives secondary amine tetrahedral intermediate, (esters, -Formation of a carboxylic and kicks off a carboxylate amides, and acid – add water ion carboxylic Product: ester, amide, or -Remember the reactivity acids) carboxylic acid chart! Since anhydrides are -Besides being able to react with an alcohol to form an ester, anhydrides can react with an less reactive than acid amine, to form an amide. chlorides, anhydrides are unable to be directly converted to an acid chloride. It can only react with a nucleophile that forms a less stable carboxylic acid derivate. Therefore, it can only react with alcohols, amines, and water to form esters, -Anhydrides can also react with water, to form 2 carboxylic acids. The other carboxylic acids is not drawn below amides, and carboxylic acids! Reactions with Esters Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Interconversi -An ester can react with an amine in an acid catalyzed mechanism. The ester will be Reactant– An ester -Know this reaction and the -on of esters protonated first to form a more electrophilic compound. Then the amine can attack the Reagent: mechanism! (amides, carbonyl carbon, forming the tetrahedral intermediate below. The alcohol will then be kicked -Formation of an amide – -Essentially follows the carboxylic off (it will be protonated first, then leave, not shown below), forming the amide. ammonia, primary or acidic catalyzed mechanism, acids secondary amine where the nucleophile -Formation of a carboxylic attacks first, forms the acid – H+ and H 2 tetrahedral intermediate, Product – either an amide and kicks off an alcohol or a carboxylic acid -Esters are relatively unreactive. They can react to form only amides, -An ester can react with acidic water, forming the similar tetrahedral intermediate. The alcohol will then leave (protonated first), and then form the carboxylic acid carboxylic acids, and other esters, which is shown below. Transesterfic -An ester can react with an alcohol under acidic conditions, to form a new ester, with a different Reactant An ester - Know this reaction and the -ation substituent attached to the alcohol. It will undergo the same acid-catalyzed mechanism, form Reagent: An alcohol and H+ mechanism! (switch R the tetrahedral intermediate, and kick off the initial alcohol attached Product: An ester, with a -The easiest way of switch a groups on an different R group attached R group on an ester ester) to the oxygen atom -Essentially follows the acidic catalyzed mechanism, where the nucleophile attacks first, forms the tetrahedral intermediate, and kicks off an alcohol Reaction of -A thiolester (S instead of O), has very similar reactivity to an ester. It is actually more reactiveReactant An thiolester -Know this reaction and the thiolesters than an ester and amide, but less reactive than an acid chloride and an anhydride. Therefore, a Reagent:-Formation of an mechanism! It is essentially thiolester can be converted into an ester, amide, or carboxylic acid. It will follow a similar ester – an alcohol the same as an ester, but mechanism of an ester. Below is a thiolester reacting with an amine, forming an amide -Formation of an amide – with a sulfur instead of a ammonia, primary or oxygen secondary amine -Thiolsulfurs are more -Formation of a carboxylic reactive than esters, but less acid – add water reactive than anhydrides Product: An ester, amide, and acid chlorides. or carboxylic acid Reaction of -Similar to acid chlorides, esters can react with Grignard reagents twice, similar to acid chlorides,Reactant An ester -Don’t need to know the Grignard’s to to form a tertiary alcohol with 2 addition of Grignards Reagent: mechanism, but know the o esters, and -Formation of 3 alcohol – reaction! reduction of Grignards -Know these reaction for esters -Formation of 1 alcohol - synthesis questions, just in LAH case Product: An ester, with a different R group attached to the oxygen atom -Similar to Carboxylic acids, esters can react with LAH to form primary alcohols. Two additions of LAH are needed to form the primary alcohol Reactions involving Amides Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Hydrolysis of -Amides are the least reactive out of all of the carboxylic acid derivatives. Therefore, an amide Reactant– An Amide - Know this reaction and the Amides can’t directly convert to an acid chloride, anhydride, thiolester, or ester. It can be converted Reagent: H+ and water mechanism! (forms back to a carboxylic acid through an acid catalyzed mechanism that requires the protonation Product – Carboxylic Acids - Can’t directly convert to an Carboxylic of the carbonyl oxygen. After formation of the tetrahedral intermediate, the amine will get acid chloride, anhydride, acid) kicked off, forming the carboxylic acid. thiolester, or ester! Can only be converted into a carboxylic acid Dehydration -Primary amides can be dehydrated using a strong dehydrating agent such as POCl or P 3 to 2 5 Reactant Amide - Don’t need to know the of Amides to form a nitrile. Amides are the only carboxylic acid derivative that can convert into an nitrile Reagent: - POCl 3r P O2 5 mechanism, but know the Nitriles Product: A nitrile reaction! - The only carboxylic acid derivative that can convert into an nitrile Review From Ch 19, Primary, Secondary or tertiary amides can be reduced by LiAlH to f4rm an amine Reactant Amide - Don’t need to know the reactions of Reagent: - LAH, or NaOH, mechanism, but know the amides (Ch and a halogen reaction! 19) Product: Amines -See the chapter 19 chart for more information. Again the mechanism is not -Primary amides can also react with halogens, -OH and water, which undergoes a important, just know the reagents, what they do and rearrangement of the carbonyl substituent so that it then attaches to the amine, forming a substituted amine. See the Ch 19 chart for more details on the mechanism what is formed Reactions with Nitriles Reaction Example (Mechanism) Reactants, Reagent, Important things to note Products Hydrolysis of -Nitriles can react under acidic hydrolysis to form carboxylic acids. Under weak conditions, it Reactant– A nitrile -Don’t need to know the Nitriles will only go to the amide form, but under strong conditions or acidic), will continue to go to Reagent: H+ and water mechanism, but know the (forming the carboxylic acid form Product – Carboxylic Acid reaction! Carboxylic -When doing this reaction, acids) will usually always go to form the carboxylic acid! Review -From Ch 19, Nitriles can react with LiAlH4to form amines Reactant– A nitrile -Don’t need to know the reactions of Reagent: mechanism, but know the Nitriles (Ch -Formation of an Amine – reaction! 19) LAH -See Ch 19 notes for more -Nitriles can also react with Grignards forming an imine first, but with further reaction under -Formation of a ketone – details acidic conditions, will form a ketone Grignards, then H+ Product – Amine or Ketone Chapter 19 – Amines Chapter 19 deals with Amines. Again, it’s a lot of reactions, but they should be too hard to understand. You will also need to be able to predict basicity, which is mentioned below. Basicity In Organic Chemistry, we can refer to basicity as how readily the base will extract a hydrogen from an acid. Essentially, the strength of the base directly relates to the stability of the conjugate acid. There are many factors to consider when dealing with the basicity of compounds. A good way to remember many of the basicity rules is that it is the OPPOSITE OF ACIDITY RULES!!! Resonance: Remember in Acidity that resonance will stabilize the carboanion formed, making the conjugate base more stable. However, in basicity, resonance will actually decrease the strength of a base. Since a base is utilizing a lone pair of electrons to extract a hydrogen, the location of the lone pair wants to remain constant. With resonance, the electrons are being delocalized around the compound, and it makes it harder for a hydrogen to be extracted because of the constant lone pair movement. o Inductive Effect: Opposite of acidity, electron-donating groups will stabilize the cation that forms as a result of extraction of a hydrogen, making the conjugate acid more stable. Electron- withdrawing groups, or very electronegative atoms will destabilize the cation formed, making the conjugate acid less stable. o Aromaticity: Don’t forget about the aromaticity of the compound/conjugate acid. If you form aromaticity after extraction of the hydrogen, the conjugate acid is stabilized by the aromaticity, increasing the strength of the base. However, if you break aromaticity after extraction of a hydrogen, the conjugate acid is now destabilized. Therefore, the compound will be unwilling to give up the hydrogen if it destroys the aromaticity of the compound. o Reactions of Amines Reaction Example (Mechanism) Reactants, Reagent, Important things to Products note Electrophili Just like benzene rings, a pyridine is another aromatic compound that can Reactant– Pyridine -Don’t need to know c Aromatic undergo electrophilic aromatic substitutions; however, pyridine is a very (similar to benzene, the mechanism, but Substitutio deactivated compound. Below is a nitration reaction with pyridine. except a Nitrogen know the reaction! n of The nitro group will preferentially be placed meta to the nitrogen to preventreplaces one of the -The mechanism is Pyridine the carbocation from forming on the nitrogen. Notice below that if a cation carbons) similar to reactions (Ch 17) does form on the nitrogen, it forms a very unstable cation because the octet Reagent: Any with benzene, but all rule is not obeyed. Therefore, any electrophilic substitution on pyridine electrophile + its electrophiles when will be place meta preferentially. lewis acid catalyst reacted with Product – pyridine will always Substituted be placed meta to pyridine, with the nitrogen! electrophile -Don’t forget the placed meta electrophiles and their lewis acid catalyst (see Ch 17 chart) Nucleophili Because pyridine is very deactivated, it is able to react in a nucleophilic Reactant- Pyridine -Don’t need to know c aromatic aromatic substitution without any more deactivating groups. A leaving group with a leaving the mechanism, but substitutio is still needed though, preferentially in the ortho/para position. This allogroup placed know the reaction! n of for stabilization of the anion, which is more stable on the nitrogen ortho/para to the -Favors ortho/para Pyridine because now it has a full octet, which is also stabilize by the more nitrogen positions (opposite electronegative nitrogen. Reagent – Any of electrophilic nucleophile (-OCH ,3 addition) which -OH, -CN, NH 3 etc…) allows the more Product – A stable carboanion Pyridine with a (nitrogen is more nucleophile electronegative than attached carbon) ortho/para, -Remember the replacing the leaving group leaving group follows electronegativity trends (F>Cl>Br>I) Alkylatio -Amines react readily with alkyl halides to form more substituted amines in Reactant: Any -Know the reaction n of SN2 reaction. Keep in mind that because the reaction is going to a SN2 unsaturated and the mechanism! amines reaction, be sure the electrophile is not attached to a tertiary carbon amine (Ammonia, -Basically a SN2 by alkyl or adjacent to a quartenary carbon. Also, if the reaction specified 1 , 2 , 3 ) reaction, but will halides stereochemistry, be sure to show the inversion of stereochemistry. Reagent: Excess of continue to react Alkyl halide (Must with excess amounts be able to react in a of alkyl halides to SN2 reaction!) form the quartenary Product: Fully amine alkylated amine -Don’t forget about (quartenary) the stereochemistry -However, after one SN2 reaction, the amine product that is formed is (Inversion of now more nucleophilic (more electron density on nitrogen), and continue configuration), if to react until it is completely alkylated. asked! -Alkyl halide must be able to react in a SN2 reaction! -The overall reaction is shown below Hofmann -As seen previously, an amine can react with an alkyl halide in a SN2 reactReactant A -Know the reaction Elminatio With excess alkyl halides, it will completely alkylate until the amine quaternary amine and the mechanism! n (E2, Ch is completely saturated (formed by -Essentially an E2 6) alkylation a reaction, but favors unsaturated amine) the Hofmann Reagent: A base product instead of (Ag 2 commonly Zaitsev’s product! used to produce – -Must have a OH ions in situ) quartenary amine Product: The least for this E2 reaction - After alkylating an amine to a quartenary amine, the amine can now react substituted alkene to occur! with a base and undergo an E2 reaction. A common reagent used is Ag O,2 (Hofmann product) which produces –OH ions which will extract an adjacent hydrogen to form an alkene. Notice that the hydrogen that is extract forms the least substituted alkene. This is because of sterics that prevents the anti- coplanar stereochemistry when trying to form the Zaitsev's product from extraction of the hydrogen from the more substituted carbon. Therefore, the only hydrogen that can be placed 180 from the amine is from the least substituted carbon, forming the least substituted alkene. This is known as the Hofmann product. -The overall reaction is shown below Oxidation Amines can be oxidized by peroxides. Depending on the saturation of the Reactant: Tertiary -Know the reaction of amine, different products can form. A primary amine can be saturated to amine (only tertiary and the mechanism! Amines: form a nitro group (Exact opposite from reducing a nitro group to amine can undergo -Must have a tertiary Cope form an amine) a Cope Elimination) amine to undergo a Eliminati Reagent: An Cope Elimination on
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