Carboxylic Acids. Carboxylic acid groups are always terminal groups with a carbonyl carbon also bound to a hydroxyl For example:

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1 Carboxylic Acids The functional group of carboxylic acids consists of a C=O with -OH bonded to the same carbon. Structure of Carboxyl Carbon is sp 2 hybridized. Bond angles are close to 120. O-H eclipsed with C=O, to get overlap of π orbital with orbital of lone pair on oxygen. Carboxyl group is usually written -COOH. Aliphatic acids have an alkyl group bonded to -COOH. Aromatic acids have an aryl group. Fatty acids are long- chain aliphatic acids. Almost all naturally occurring acids are carboxylic acids (-CO 2 H). Carboxylic acid groups are always terminal groups with a carbonyl carbon also bound to a hydroxyl group. For example: Formic acid is the principal ingredient and stinging agent of most ant bites. Benzoic acid is found in many plants: for example, the Voodoo lily uses it to attract insects needed for pollination. Stearic acid is found in beef tallow (fat) and (after reaction with NaOH) is one of the active components in old lye soap as well as modern soaps (sodium tallowate appears on the ingredient labels of soaps, it is a mixture of several similar sodium salts of carboxylic acids, one of which is sodium stearate). 112

2 Dicarboxylic acids have 2 -CO 2 H groups and tricarboxylic acids have 3 -CO 2 H groups (citric acid has 3 -CO 2 H groups). Nomenclature 1. Common Names Many aliphatic acids have historical names. Some common names HCO 2 H formic acid L. formica ant CH 3 CO 2 H acetic acid L. acetum vinegar CH 3 CH 2 CO 2 H propionic acid G. first salt CH 3 CH 2 CH 2 CO 2 H butyric acid L. butyrum butter CH 3 CH 2 CH 2 CH 2 CO 2 H valeric acid L. valerans Positions of substituents on the chain are labeled with Greek letters Cl O CH 3 CH 2 CHC OH α-chlorobutyric acid 113

3 IUPAC Names 1-Remove -e from alkane (or alkene) name, add -oic acid.the carbon of the carboxyl group is #1. HCOOH CH 3 CO 2 H CH 3 CH 2 CO 2 H methanoic acid ethanoic acid propanoic acid CH 3 CH 3 CHCOOH 2-methylpropanoic acid Br CH 3 CH 2 CHCO 2 H 2-bromobutanoic acid Cl O CH 3 CH 2 CHC OH 2-chlorobutanoic acid 2-Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids. 3-Aromatic acids are named as benzoic acids. C O O H COOH C H (C H 3 ) 2 2-isopropylcyclopentanecarboxylic acid OH o-hydroxybenzoic acid (Salicylic acid) 114

4 Some Important Acids Acetic acid is in vinegar and other foods, used industrially as solvent, catalyst, and reagent for synthesis. Fatty acids from fats and oils. Benzoic acid in drugs, preservatives. Adipic acid used to make nylon 66. Phthalic acid used to make polyesters Physical properties Carboxylic acids hydrogen bond to themselves to form a dimer: Carboxylic acids also form hydrogen bonds to water molecules: Since carboxylic acids can form more than one set of hydrogen bonds, their boiling points are usually higher than those of other molecules of the same molecular weight (MW). Low-MW carboxylic acids are generally liquids at room temp. (often, they are somewhat oily); higher- MW carboxylic acids are generally waxy solids. Carboxylic acids with 12 to 20 carbon atoms are often referred to as fatty acids, since they are found in the triglycerides in fats and oils (more later). Short-chain carboxylic acids are also generally more soluble in water than compounds of similar MW, since they can hydrogen bond to more than one water molecule. As the number of carbons in a carboxylic acid series becomes greater, the boiling point increases and the solubility in water decrease. Many carboxylic acids that are liquids at room temperature have characteristically sharp or unpleasant odors. 115

5 Ethanoic acid/acetic acid is the main ingredient in vinegar. Butanoic acid is partially responsible for the odor of locker rooms and unwashed socks. Hexanoic acid is responsible for the odor of Limburger cheese. Like most acids, carboxylic acids tend to have a sour taste (e.g., vinegar, citric acid, etc.) Acidity of Carboxylic Acids Since all carboxylic acids are weak acids, all exist in equilibrium in water. The generic equilibrium equation is: Where [H 3 O + ] [H + ]. (Recall that the water does not change concentration and therefore is incorporated into the Ka constant.) Most simple carboxylic acids have acid dissociation constants equal to about Such a small K a means that very little of the acid is ionized in water. Nonetheless, carboxylic acids are much stronger acids than phenols (typical K a = ). Carboxylic acids react with bases, but only strong bases completely remove the proton (hydrogen ion) from the acid group. The resulting carboxylate ion is then a weak base. When a strong acid is added to a solution containing carboxylate ions, the acid protonates it, regenerating the parent carboxylic acid. As we saw earlier, small carboxylic acids are quite water soluble. However, these acids don t normally reside in our bodies (except sometimes as food, e.g. acetic acid (vinegar)). The carboxylic acids that are found in human tissue are typically fatty acids. These are acids with long carbon chains that cause them to have very low solubility. When a proton is removed from a fatty acid, the resulting carboxylate ion will always have a significantly higher solubility (even if in absolute terms the solubility is still low). 116

6 Preparation of acids 1- From the oxidation of alkylbenzenes 2- from the oxidation of the alkenes and alkynes 117

7 3- from the oxidation of aldehydes 4- From the oxidation of the primary alcohols 5- from hydrolysis of nitriles 118

8 6- From the carboxylation of the Grignards Carboxylic acids, reactions: 1. as acids 2. conversion into functional derivatives a) acid chlorides b) esters c) amides d) anhydrides 3. reduction 4. alpha-halogenation 5. EAS 1. as acids: a) with active metals RCO 2 H + Na RCO - 2 Na + + H 2 (g) b) with bases RCO 2 H + NaOH RCO - 2 Na + + H 2 O c) Relative acid strength? 119

9 CH 4 < NH 3 < HC CH < ROH < HOH < H 2 CO 3 < RCO 2 H < HF d) quantitative HA + H 2 O H 3 O + + A - ionization in water Ka = [H 3 O + ][A - ]/[HA] 2. Conversion into functional derivatives: The group bonded to the acyl carbon determines the class of compound: a -OH, carboxylic acid b -Cl, acid chloride c -OR, ester d -NH 2, amide e- OCOR acid anhydride These interconvert via nucleophilic acyl substitution. Esterification Acid + alcohol yields ester + water. Acid catalyzed for weak nucleophile. All steps are reversible. Reaction reaches equilibrium. 120

10 Amides are synthesized by first reacting a carboxylic acid with ammonia, NH 3. The product, an ammonium carboxylate salt, when heated releases water: Acid Chlorides An activated form of the carboxylic acid. Chloride is a good leaving group, so undergoes acyl substitution easily. To synthesize acid chlorides use thionyl chloride, oxalyl chloride or phosphorous pentachloride with the acid. Anhydrides Removing water from a carboxylic acid can make an anhydride. 121

11 3- Reduc!on to 1 Alcohols Use strong reducing agent, LiAlH4. Borane, BH3 in THF, reduces carboxylic acid to alcohol, but does not reduce ketone 4. Alpha-halogenations halogenations: (Hell-Volhard-Zelinsky reaction) RCH2COOH + X2, P RCHCOOH + HX X α-haloacid X2 = Cl2, Br2 5. EAS: (-COOH COOH is deactivating and meta- directing) 122

12 Phenols Ar-OH Phenols are compounds with an OH group attached to an aromatic carbon. Although they share the same functional group with alcohols, where the OH group is attached to an aliphatic carbon, the chemistry of phenols is very different from that of alcohols. Nomenclature. Phenols are usually named as substituted phenols. The methylphenols are given the special name, cresols. Some other phenols are named as hydroxy compounds. Physical properties Phenols are polar and can hydrogen bond. Phenols are water insoluble. Phenols are stronger acids than water and will dissolve in 5% NaOH. Phenols are weaker acids than carbonic acid and do not dissolve in 5% NaHCO 3. Intramolecular hydrogen bonding is possible in some orthosubstituted phenols. This intramolecular hydrogen bonding reduces water solubility and increases volatility. Thus, o-nitrophenol is steam distillable while the isomeric p-nitrophenol is not. 123

13 Reactions: alcohols phenols 1. HX NR 2. PX 3 NR 3. dehydration NR 4. as acids phenols are more acidic 5. ester formation similar 6. oxidation NR 124

14 Phenols, reactions: 1. as acids 2. ester formation 3. ether formation 4. EAS a) nitration f) nitrosation b) sulfonation g) coupling with diaz. salts c) halogenation h) Kolbe d) Friedel-Crafts alkylation i) Reimer-Tiemann e) Friedel-Crafts acylation 125

15 We use the ionization of acids in water to measure acid strength (Ka): HBase + H 2 O H 3 O + + Base - Ka = [H 3 O + ][ Base ]/[ HBase] ROH Ka ~ ArOH Ka ~ Why are phenols more acidic than alcohols? 126

16 Resonance stabilization of the phenoxide ion, lowers the PE of the products of the ionization, decreases the ΔH, shifts the equal farther to the right, makes phenol more acidic than an alcohol Effect of substituent groups on acid strength? Electron withdrawing groups will decrease the negative charge in the phenoxide, lowering the PE, decreasing the ΔH, shifting the equal farther to the right, stronger acid. Electron donating groups will increase the negative charge in the phenoxide, increasing the PE, increasing the ΔH, shifting the equilibrium to the left, weaker acid. Number the following acids in decreasing order of acid strength (let # 1 = most acidic, etc.) 127

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19 At low temperature the reaction is non-reversible and the lower Eact orthoproduct is formed (rate control). At high temperature the reaction is reversible and the more stable paraproduct is formed (kinetic control). 130

20 f) nitrosation g) coupling with diazonium salts (EAS with the weak electrophile diazonium) 131

21 h) Kolbe reaction (carbonation) i) Reimer-Tiemann reaction 132

22 Amines Structure, Naming, and Physical Properties Amines are one of the six nitrogen-containing functional groups we use (amide, nitrile, imine, azide, and nitro are the others.) Structure An amine has an sp3-hybridized nitrogen with three bonds and a lone pair of electrons. As a result of the sp3-hybridization, bond angles around the nitrogen are approximately 109.5º (typically a li le smaller, such as 107º). Amines exhibit an unusual inversion at room temperature, so we will not observe chirality at the nitrogen of a neutral amine. Besides ammonia, which is the simplest amine, substituted amines are categorized as: Primary if they have one bond from nitrogen to carbon (H 2 NR) Secondary if they have two bonds from nitrogen to carbon (HNR 2 ), and Tertiary if they have three bonds from nitrogen to carbon (NR 3 ). Naming Official IUPAC name is based on analogous alcohol. The -ol ending gets replaced by -amine. 133

23 Two common naming systems: 1) alkyl precedes the word amine 2) amino (-NH 2 ) substituent on a parent alkane. For secondary and tertiary amines, the longest continuous carbon chain acts as the parent, and an N locant is used to describe the position of the extra alkyl groups, which are listed in alphabetical order at the beginning of the name. (In the common system, simply list the alkyl groups before the word amine. ) Aniline is the IUPAC and common name for the aromatic amine C 6 H 5 NH 2, which is used a parent compound for other aromatic amines. Ammonium salts are tetrasubstituted, cationic versions of amines: 134

24 Physical Properties Amines are slightly basic. This because they have a lone pair of electrons to donate to a proton. This same feature makes them nucleophiles. RNH 2 + H OH RNH 3 + OH Kb = [RNH 3 ] [OH ] [RNH 2 ] Typical amines have K b values = 10-3 to 10-4 Water solubility: Amines are mostly insoluble in water; however, those with fewer than ~5 carbon atoms are water soluble. (With fewer than ~5 carbon atoms, the polarity of the N-part of the molecule dominates over the nonpolar hydrocarbon part of the molecule.) Boiling point/melting point. Hydrogen bonding is possible in amines that contain NH or NH 2 groups. An NH 2 exhibits stronger hydrogen bonding than an NH. However, when comparing amines to alcohols, an OH group exhibits stronger hydrogen bonding than an NH 2, since oxygen is more electronegative than nitrogen. Preparation of amines 1-Reduction of Nitriles Nitriles may be reduced with lithium aluminum hydride to generate primary amines. 135

25 2- Reduction of Amides Amides may be reduced with LiAlH4 to generate subs tuted amines. 3-Reduction of Nitro Compounds Nitro groups may be reduced by H 2 and palladium on carbon to generate amines. This reaction is particularly useful for aromatic systems because of the ease of installing a nitro group selectively. 4-The Hofmann Rearrangement The Hofmann rearrangement allows us to shorten a chain by one carbon by the conversion of an amide to a primary amine. The overall conversion and the mechanism are given below. 5-The Gabriel Amine Synthesis 136

26 This phthalimide derivative may then be hydrolyzed with aqueous base to generate phthalic acid and the desired primary amine. Alternatively, the phthalimide may be heated with hydrazine to generate the free amine. 137