Presentation on theme: "Carboxylic Acids and the Acidity of the O—H Bond"— Presentation transcript:
1Carboxylic Acids and the Acidity of the O—H Bond Structure and BondingCarboxylic acids are compounds containing a carboxy group (COOH).The structure of carboxylic acids is often abbreviated as RCOOH or RCO2H, but keep in mind that the central carbon atom of the functional group is doubly bonded to one oxygen atom and singly bonded to another.
2Structure and BondingThe C—O single bond of a carboxylic acid is shorter than the C—O bond of an alcohol.This can be explained by looking at the hybridization of the respective carbon atoms.Because oxygen is more electronegative than either carbon or hydrogen, the C—O and O—H bonds are polar.
3Nomenclature—The IUPAC System In the IUPAC system, carboxylic acids are identified by a suffix added to the parent name of the longest chain with different endings being used depending on whether the carboxy group is bonded to a chain or a ring.If the COOH is bonded to a chain, find the longest chain containing the COOH, and change the “e” ending of the parent alkane to the suffix “oic acid”.If the COOH is bonded to a ring, name the ring and add the words “carboxylic acid”.Number the carbon chain or ring to put the COOH group at C1, but omit this number from the name.Apply all the other usual rules of nomenclature.
5Greek letters are used to designate the location of substituents in common names. The carbon adjacent to the COOH is called the carbon, followed by the carbon, followed by the carbon, the carbon and so forth down the chain.The last carbon in the chain is sometimes called the carbon.The carbon in the common system is numbered C2 in the IUPAC system.
6Compounds containing two carboxy groups are called diacids Compounds containing two carboxy groups are called diacids. Diacids are named using the suffix –dioic acid.Metal salts of carboxylate anions are formed from carboxylic acids in many reactions. To name the metal salt of a carboxylate anion, put three parts together:
7Figure 19.2Naming the metal salts ofcarboxylate anions
8Physical PropertiesCarboxylic acids exhibit dipole-dipole interactions because they have polar C—O and O—H bonds.They also exhibit intermolecular hydrogen bonding.Carboxylic acids often exist as dimers held together by two intermolecular hydrogen bonds.Figure 19.3Two molecules of acetic acid(CH3COOH) held together bytwo hydrogen bonds
9Spectroscopic Properties Carboxylic acids have very characteristic IR and NMR absorptions.In the IR:-The C=O group absorbs at ~ 1710 cm-1.-The O—H absorption occurs from cm-1.In the 1H NMR:-The O—H proton absorbs between ppm.-The protons absorb between ppm.In the 13C NMR, the C=O appears at ppm.
10Figure 19.4The IR spectrum of butanoicacid, CH3CH2CH2COOH
11Preparation of Carboxylic Acids  Oxidation of 1° alcohols Oxidation of alkyl benzenes
13Reactions of Carboxylic Acids The most important reactive feature of a carboxylic acid is its polar O—H bond, which is readily cleaved with base.
14The nonbonded electron pairs on oxygen create electron-rich sites that can be protonated by strong acids (H—A).Protonation occurs at the carbonyl oxygen because the resulting conjugate acid is resonance stabilized (Possibility ).The product of protonation at the OH group (Possibility ) cannot be resonance stabilized.
15The polar C—O bonds make the carboxy carbon electrophilic The polar C—O bonds make the carboxy carbon electrophilic. Thus, carboxylic acids react with nucleophiles.Nucleophilic attack occurs at an sp2 hybridized carbon atom, so it results in the cleavage of the bond as well.
16Carboxylic Acids—Strong Organic BrØnsted-Lowry Acids Carboxylic acids are strong organic acids, and as such, readily react with BrØnsted-Lowry bases to form carboxylate anions.
17An acid can be deprotonated by a base that has a conjugate acid with a higher pKa. Because the pKa values of many carboxylic acids are ~5, bases that have conjugate acids with pKa values higher than 5 are strong enough to deprotonate them.
19Carboxylic acids are relatively strong acids because deprotonation forms a resonance-stabilized conjugate base—a carboxylate anion.The acetate anion has two C—O bonds of equal length (1.27 Å) and intermediate between the length of a C—O single bond (1.36 Å) and C=O (1.21 Å).
20Resonance stabilization accounts for why carboxylic acids are more acidic than other compounds with O—H bonds—namely alcohols and phenols.To understand the relative acidity of ethanol, phenol and acetic acid, we must compare the stability of their conjugate bases and use the following rule:- Anything that stabilizes a conjugate base A:¯ makes the starting acid H—A more acidic.
21Ethoxide, the conjugate base of ethanol, bears a negative charge on the O atom, but there are no additional factors to further stabilize the anion. Because ethoxide is less stable than acetate, ethanol is a weaker acid than acetic acid.Phenoxide, the conjugate base of phenol, is more stable than ethoxide, but less stable than acetate because acetate has two electronegative O atoms upon which to delocalize the negative charge, whereas phenoxide has only one.
22Figure 19.7Summary: The relationshipbetween acidity and conjugatebase stability for acetic acid,phenol, and ethanolNote that although resonance stabilization of the conjugate base is important in determining acidity, the absolute number of resonance structures alone is not what is important!
23The Inductive Effect in Aliphatic Carboxylic Acids
25Substituted Benzoic Acids Recall that substituents on a benzene ring either donate or withdraw electron density, depending on the balance of their inductive and resonance effects. These same effects also determine the acidity of substituted benzoic acids. Electron-donor groups destabilize a conjugate base, making an acid less acidic—The conjugate base is destabilized because electron density is being donated to a negatively charged carboxylate anion.
26 Electron-withdrawing groups stabilize a conjugate base, making an acid more acidic. The conjugate base is stabilized because electron density is removed from the negatively charged carboxylate anion.
27Figure 19.8 How common substituents affect the reactivity of a benzene ring towardselectrophiles and the acidity ofsubstituted benzoic acids
28Sulfonic Acids Sulfonic acids have the general structure RSO3H. The most widely used sulfonic acid is p-toluenesulfonic acid.Sulfonic acids are very strong acids because their conjugate bases (sulfonate anions) are resonance stabilized, and all the resonance structures delocalize negative charge on oxygen.
29Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation and Reduction Two broad classes of compounds contain the carbonyl group: Compounds that have only carbon and hydrogen atoms bonded to the carbonyl Compounds that contain an electronegative atom bonded to the carbonyl
30The presence or absence of a leaving group on the carbonyl determines the type of reactions the carbonyl compound will undergo.Carbonyl carbons are sp2 hybridized, trigonal planar, and have bond angles that are ~1200. In these ways, the carbonyl group resembles the trigonal planar sp2 hybridized carbons of a C=C.
31In one important way, the C=O and C=C are very different. The electronegative oxygen atom in the carbonyl group means that the bond is polarized, making the carbonyl carbon electron deficient.Using a resonance description, the carbonyl group is represented by two resonance structures.
32General Reactions of Carbonyl Compounds Carbonyls react with nucleophiles.
33Aldehydes and ketones react with nucleophiles to form addition products by a two-step process: nucleophilic attack followed by protonation.
34The net result is that the bond is broken, two new bonds are formed, and the elements of H and Nu are added across the bond.Aldehydes are more reactive than ketones towards nucleophilic attack for both steric and electronic reasons.
35Carbonyl compounds with leaving groups react with nucleophiles to form substitution products by a two-step process: nucleophilic attack, followed by loss of the leaving group.The net result is that Nu replaces Z, a nucleophilic substitution reaction. This reaction is often called nucleophilic acyl substitution.
37Nucleophilic addition and nucleophilic acyl substitution involve the same first step—nucleophilic attack on the electrophilic carbonyl carbon to form a tetrahedral intermediate.The difference between the two reactions is what then happens to the intermediate.Aldehydes and ketones cannot undergo substitution because they do not have a good leaving group bonded to the newly formed sp3 hybridized carbon.
38Preview of Oxidation and Reduction Carbonyl compounds are either reactants or products in oxidation-reduction reactions.
39The three most useful oxidation and reduction reactions of carbonyl starting materials can be summarized as follows:
40Reduction of Aldehydes and Ketones The most useful reagents for reducing aldehydes and ketones are the metal hydride reagents.Treating an aldehyde or ketone with NaBH4 or LiAlH4, followed by H2O or some other proton source affords an alcohol.
41The net result of adding H:¯ (from NaBH4 or LiAlH4) and H+ (from H2O) is the addition of the elements of H2 to the carbonyl bond.
42Catalytic hydrogenation also reduces aldehydes and ketones to 1° and 2° alcohols respectively, using H2 and a catalyst.When a compound contains both a carbonyl group and a carbon—carbon double bond, selective reduction of one functional group can be achieved by proper choice of the reagent.A C=C is reduced faster than a C=O with H2 (Pd-C).A C=O is readily reduced with NaBH4 and LiAlH4, but a C=C is inert.
43Thus, 2-cyclohexenone, which contains both a C=C and a C=O, can be reduced to three different compounds depending upon the reagent used.
44The Stereochemistry of Carbonyl Reduction Hydride converts a planar sp2 hybridized carbonyl carbon to a tetrahedral sp3 hybridized carbon.
45Enantioselective Carbonyl Reductions Selective formation of one enantiomer over another can occur if a chiral reducing agent is used.A reduction that forms one enantiomer predominantly or exclusively is an enantioselective or asymmetric reduction.An example of chiral reducing agents are the enantiomeric CBS reagents.
46CBS refers to Corey, Bakshi and Shibata, the chemists who developed these versatile reagents. One B—H bond serves as the source of hydride in this reduction.The (S)-CBS reagent delivers H:- from the front side of the C=O. This generally affords the R alcohol as the major product.The (R)-CBS reagent delivers H:- from the back side of the C=O. This generally affords the S alcohol as the major product.
47These reagents are highly enantioselective These reagents are highly enantioselective. For example, treatment of propiophenone with the (S)-CBS reagent forms the R alcohol in 97% ee.
48Reduction of Carboxylic Acids and Their Derivatives LiAlH4 is a strong reducing agent that reacts with all carboxylic acid derivatives.Diisobutylaluminum hydride ([(CH3)2CHCH2]2AlH, abbreviated DIBAL-H, has two bulky isobutyl groups which makes this reagent less reactive than LiAlH4.Lithium tri-tert-butoxyaluminum hydride, LiAlH[OC(CH3)3]3, has three electronegative O atoms bonded to aluminum, which makes this reagent less nucleophilic than LiAlH4.
49Acid chlorides and esters can be reduced to either aldehydes or 1° alcohols depending on the reagent.
50In the reduction of an acid chloride, Cl¯ comes off as the leaving group. In the reduction of the ester, CH3O¯ comes off as the leaving group, which is then protonated by H2O to form CH3OH.
51The mechanism illustrates why two different products are possible.
52Carboxylic acids are reduced to 1° alcohols with LiAlH4. LiAlH4 is too strong a reducing agent to stop the reaction at the aldehyde stage, but milder reagents are not strong enough to initiate the reaction in the first place.
53Unlike the LiAlH4 reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlH4 reduction of amides forms amines.Since ¯NH2 is a very poor leaving group, it is never lost during the reduction, and therefore an amine is formed.
56Oxidation of Aldehydes A variety of oxidizing agents can be used, including CrO3, Na2Cr2O7, K2Cr2O7, and KMnO4.Aldehydes can also be oxidized selectively in the presence of other functional groups using silver(I) oxide in aqueous ammonium hydroxide (Tollen’s reagent). Since ketones have no H on the carbonyl carbon, they do not undergo this oxidation reaction.
57Organometallic Reagents Other metals in organometallic reagents are Sn, Si, Tl, Al, Ti, and Hg. General structures of the three common organometallic reagents are shown:
58Since both Li and Mg are very electropositive metals, organolithium (RLi) and organomagnesium (RMgX) reagents contain very polar carbon—metal bonds and are therefore very reactive reagents.Organomagnesium reagents are called Grignard reagents.Organocopper reagents (R2CuLi), also called organocuprates, have a less polar carbon—metal bond and are therefore less reactive. Although they contain two R groups bonded to Cu, only one R group is utilized in the reaction.In organometallic reagents, carbon bears a - charge.
59Organolithium and Grignard reagents are typically prepared by reaction of an alkyl halide with the corresponding metal.With lithium, the halogen and metal exchange to form the organolithium reagent. With Mg, the metal inserts in the carbon—halogen bond, forming the Grignard reagent.
60Grignard reagents are usually prepared in diethyl ether (CH3CH2OCH2CH3) as solvent. It is thought that two ether O atoms complex with the Mg atom, stabilizing the reagent.
61Organocuprates are prepared from organolithium reagents by reaction with a Cu+ salt, often CuI.
62Acetylide ions are another example of organometallic reagents. Acetylide ions can be thought of as “organosodium reagents”.Since sodium is even more electropositive than lithium, the C—Na bond of these organosodium compounds is best described as ionic, rather than polar covalent.
63An acid-base reaction can also be used to prepare sp hybridized organolithium compounds. Treatment of a terminal alkyne with CH3Li affords a lithium acetylide.The equilibrium favors the products because the sp hybridized C—H bond of the terminal alkyne is more acidic than the sp3 hybridized conjugate acid, CH4, that is formed.
64Organometallic reagents are strong bases that readily abstract a proton from water to form hydrocarbons.Similar reactions occur with the O—H proton of alcohols and carboxylic acids, and the N—H protons of amines.
65Since organolithium and Grignard reagents are themselves prepared from alkyl halides, a two-step method converts an alkyl halide into an alkane (or other hydrocarbon).Organometallic reagents are also strong nucleophiles that react with electrophilic carbon atoms to form new carbon—carbon bonds.These reactions are very valuable in forming the carbon skeletons of complex organic molecules.
66Examples of functional group transformations involving organometallic reagents:  Reaction of R—M with aldehydes and ketones to afford alcohols Reaction of R—M with carboxylic acid derivatives
67 Reaction of R—M with other electrophilic functional groups
68Reaction of Organometallic Reagents with Aldehydes and Ketones. Treatment of an aldehyde or ketone with either an organolithium or Grignard reagent followed by water forms an alcohol with a new carbon—carbon bond.This reaction is an addition because the elements of R’’ and H are added across the bond.
69This reaction follows the general mechanism for nucleophilic addition—that is, nucleophilic attack by a carbanion followed by protonation.Mechanism 20.6 is shown using R’’MgX, but the same steps occur with RLi reagents and acetylide anions.
70Note that these reactions must be carried out under anhydrous conditions to prevent traces of water from reacting with the organometallic reagent.
71This reaction is used to prepare 1°, 2°, and 3° alcohols.
72Protecting GroupsAddition of organometallic reagents cannot be used with molecules that contain both a carbonyl group and N—H or O—H bonds.Carbonyl compounds that also contain N—H or O—H bonds undergo an acid-base reaction with organometallic reagents, not nucleophilic addition.
73Solving this problem requires a three-step strategy:  Convert the OH group into another functional group that does not interfere with the desired reaction. This new blocking group is called a protecting group, and the reaction that creates it is called “protection.” Carry out the desired reaction. Remove the protecting group. This reaction is called “deprotection.”A common OH protecting group is a silyl ether.
74tert-Butyldimethylsilyl ethers are prepared from alcohols by reaction with tert-butyldimethylsilyl chloride and an amine base, usually imidazole.The silyl ether is typically removed with a fluoride salt such as tetrabutylammonium fluoride (CH3CH2CH2CH2)4N+F¯.
75The use of tert-butyldimethylsilyl ether as a protecting group makes possible the synthesis of 4-methyl-1,4-pentanediol by a three-step sequence.
76Figure 20.7General strategy for using aprotecting group
77Reaction of Organometallic Reagents with Carboxylic Acid Derivatives. Both esters and acid chlorides form 3° alcohols when treated with two equivalents of either Grignard or organolithium reagents.
79To form a ketone from a carboxylic acid derivative, a less reactive organometallic reagent—namely an organocuprate—is needed.Acid chlorides, which have the best leaving group (Cl¯) of the carboxylic acid derivatives, react with R’2CuLi to give a ketone as the product.Esters, which contain a poorer leaving group (¯OR), do not react with R’2CuLi.
80Reaction of Organometallic Reagents with Other Compounds Grignards react with CO2 to give carboxylic acids after protonation with aqueous acid.This reaction is called carboxylation.The carboxylic acid formed has one more carbon atom than the Grignard reagent from which it was prepared.
81The mechanism resembles earlier reactions of nucleophilic Grignard reagents with carbonyl groups.
82Like other strong nucleophiles, organometallic reagents—RLi, RMgX, and R2CuLi—open epoxide rings to form alcohols.
83The reaction follows the same two-step process as opening of epoxide rings with other negatively charged nucleophiles—that is, nucleophilic attack from the back side of the epoxide, followed by protonation of the resulting alkoxide.In unsymmetrical epoxides, nucleophilic attack occurs at the less substituted carbon atom.
84,-Unsaturated Carbonyl Compounds ,-Unsaturated carbonyl compounds are conjugated molecules containing a carbonyl group and a C=C separated by a single bond.Resonance shows that the carbonyl carbon and the carbon bear a partial positive charge.
85This means that ,-unsaturated carbonyl compounds can react with nucleophiles at two different sites.
86The steps for the mechanism of 1,2-addition are exactly the same as those for the nucleophilic addition of an aldehyde or a ketone—that is, nucleophilic attack, followed by protonation.
88Consider the conversion of a general enol A to the carbonyl compound B Consider the conversion of a general enol A to the carbonyl compound B. A and B are tautomers: A is the enol form and B is the keto form of the tautomer.Equilibrium favors the keto form largely because the C=O is much stronger than a C=C. Tautomerization, the process of converting one tautomer into another, is catalyzed by both acid and base.
92Summary of the Reactions of Organometallic Reagents  Organometallic reagents (R—M) attack electrophilic atoms, especially the carbonyl carbon.
93 After an organometallic reagent adds to the carbonyl group, the fate of the intermediate depends on the presence or absence of a leaving group. The polarity of the R—M bond determines the reactivity of the reagents:—RLi and RMgX are very reactive reagents.—R2CuLi is much less reactive.
94SynthesisFigure 20.8Conversion of 2–hexanol intoother compounds
95Give the IUPAC name for each compound. 3,3’-dimethylhexanoic acidb)4-chloropetanoic acidc)2,4-diethylhexanoic acid
10619.13) Which of the following bases are strong enough to deprotonate CH3COOH? a) F-pka of CH3COOH is 4.8.b) (CH3)3CO-b) has a pka of 18c) has a pka of 50d) has a pka of 38c) CH3-d) NH2-pka of conjugate acid must be greater than that of the carboxylic acid being deprotonated.e) Cl-
10719.14) Rank the labeled protons in order of increasing acidity. Ha<Hb<HcThe more stable the conjugate base the more acidic the proton.
10819. 15) Match each pka value with each carboxylic acid. (3. 2, 4 19.15) Match each pka value with each carboxylic acid.(3.2, 4.9 and 0.2)CH3CH2COOHCF3COOHICH2COOH220.127.116.11Electron withdrawing groups make acids more acidic.
10919.16) Why is formic acid more acidic than acetic acid? The methyl group is electron donating and stabilizes the acid while destabilizing the conjugate base thus making it less acidic.
11019.17) Rank the compounds within each group in order of decreasing acidity. a) CH3COOH, HSCH2COOH, HOCH2COOHb) ICH2COOH, I2CHCOOH, ICH2CH2COOh
11119.18) Rank each group of compounds in order of decreasing acidity. b)
11219.19) Is the following compound more or less acidic than phenol? The more electron donating groups present, the less acidic a compound is. This compound has an additional hydroxy and alkyl group, both electron donating. So it is less acidic.
11319.22) Comparing CF3SO3H and CH3SO3H, which has the weaker conjugate base? Which conjugate base is the better leaving group? Which of these acids has the higher pka?CF3SO3H is the weaker conjugate base.CF3SO3H is the better leaving group because it is the weaker conjugate base.CH3SO3H, with the electron donating methyl group, has the higher pka and is thus a weaker acid.
11420. 1) What type of orbitals make up the indicated bonds 20.1) What type of orbitals make up the indicated bonds? And in what orbitals do the lone pairs on the oxygen lie?a. sp3-sp2b. sp2-sp2, p-pc. sp3-sp2The lone pairs lie in sp2 hybridized orbitals.
11520.2) Which compounds undergo nucleophilic addition and which substitution?
11620.3) Which compound in each pair is more reactive toward nucleuphilic attack? b)c)d)
11720.4) What alcohol is formed when each compound is treated with NaBH4 in MeOH?
11820.5) What aldehyde or ketone is needed to synthesize each alcohol by metal hydride reduction?
11920.6) Why can’t 1-methylcyclohexanol be prepared from a carbonyl by reduction? Tertiary alcohols can not be made by reduction of a carbonyl because there are no hydrogens on the carbon with the -OH.
12020.7) Draw the products of the following reactions? b)c)d)
12220.8) Draw the products when the following compounds are treated with NaBH4 in MeOH.
12320.9) What reagent is needed to carry out the reaction below? Two reagents are needed to carry out this reaction. First, the (S)-CBS reagent to produce the R-enantiomer. Followed by H2O to protonate the alcohol.
12420.10) Draw a stepwise mechanism for the following reaction.
12520.11) Draw an acid chloride and an ester that can be used to produce each product.
12620.12) Draw the products of LiAlH4 reduction of each compound. b)c)
13420.17) Write out the rea tions needed to convert CH3CH2Br to each of the following reagents.
13520.18) 1-octyne reacts readily with NaH, forming a gas that bubbles out of the reaction mixture. 1-octyne also reacts with CH3MgBr and a different gas is produced. Write out balanced equations for each reaction.
13620.19) Draw the product of the following reactions. b)c)