8● CHAPTER 22 AMINES itrogen-containing compounds are essential to life. Their ultimate source is atmo- spheric nitrogen which, by a process known as nitrogen fixation, is reduced to ammonia, then converted to organic nitrogen compounds. This chapter describes the chemistry of amines, organic derivatives of ammonia. Alkylamines have their nitro- gen attached to sp-hybridized carbon; arylamines have their nitrogen attached to an sp--hybridized carbon of a benzene or benzene-like ring R=alkyl group Ar= aryl group Amines, like ammonia, are weak bases. They are, however, the strongest uncharged bases found in significant quantities under physiological conditions. Amines are usually the bases involved in biological acid-base reactions; they are often the nucleophiles in biological nucleophilic substitutions Our word""was coined in 1912 in the belief that the substances present in the diet that prevented scurvy, pellagra, beriberi, rickets, and other diseases were"vital amines. "In many cases, that belief was confirmed; certain vitamins did prove to amines. In many other cases, however, vitamins were not amines. Nevertheless, the name vitamin entered our language and stands as a reminder that early chemists recognized the crucial place occupied by amines in biological processes. 858 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
CHAPTER 22 AMINES Nitrogen-containing compounds are essential to life. Their ultimate source is atmospheric nitrogen which, by a process known as nitrogen fixation, is reduced to ammonia, then converted to organic nitrogen compounds. This chapter describes the chemistry of amines, organic derivatives of ammonia. Alkylamines have their nitrogen attached to sp3 -hybridized carbon; arylamines have their nitrogen attached to an sp2 -hybridized carbon of a benzene or benzene-like ring. Amines, like ammonia, are weak bases. They are, however, the strongest uncharged bases found in significant quantities under physiological conditions. Amines are usually the bases involved in biological acid–base reactions; they are often the nucleophiles in biological nucleophilic substitutions. Our word “vitamin” was coined in 1912 in the belief that the substances present in the diet that prevented scurvy, pellagra, beriberi, rickets, and other diseases were “vital amines.” In many cases, that belief was confirmed; certain vitamins did prove to be amines. In many other cases, however, vitamins were not amines. Nevertheless, the name vitamin entered our language and stands as a reminder that early chemists recognized the crucial place occupied by amines in biological processes. R N R alkyl group: alkylamine Ar N Ar aryl group: arylamine 858 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
22.1 Amine Nomenclature 22.1 AMINE NOMENCLATURE Unlike alcohols and alkyl halides, which are classified as primary, secondary, or tertiary according to the degree of substitution at the carbon that bears the functional group, amines are classified according to their degree of substitution at nitrogen. An amine with one carbon attached to nitrogen is a primary amine, an amine with two is a secondary amine, and an amine with three is a tertiary amine Teri The groups attached to nitrogen may be any combination of alkyl or aryl groups Amines are named in two main ways, in the IUPAC system: either as alkylamines or as alkanamines. When primary amines are named as alkylamines, the ending -amine is added to the name of the alkyl group that bears the nitrogen. When named as alkan- amines, the alkyl group is named as an alkane and the -e ending replaced by -amine CH3CHNH CH3CHCH,CH,CH3 Ethylamine Cyclohexylamine I-Methylbutylamine (ethanamine) (cyclohexanamine) (2-pentanamine) PROBLEM 22 1 Give an acceptable alky lamine or alkanamine name for each of the following amines: (a)CH5 CH2NH (b)CsHs CHNH2 (c CH2=CHCH2NH SAMPLE SOLUTION (a)The amino substituent is bonded to an ethyl group that ears a phenyl substituent at C-2. the compound CsHs CH2 CH2 NH2 may be named as either 2-phenylethylamine or 2-phenylethanamine Aniline is the parent IUPAC name for amino-substituted derivatives of benzene Substituted derivatives of aniline are numbered beginning at the carbon that bears the 1826 as a degradation prod amino group. Substituents are listed in alphabetical order, and the direction of number- uct of indigo, a dark blue g is governed by the usual"first point of difference"rule. ye obtained from the West from which the name aniline NH NH, Br CHCH p-Fluoroaniline 5-Bromo-2-ethylaniline Arylamines may also be named as arenamines. Thus, benzenamine is an alterna tive, but rarely used, name for aniline. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
22.1 AMINE NOMENCLATURE Unlike alcohols and alkyl halides, which are classified as primary, secondary, or tertiary according to the degree of substitution at the carbon that bears the functional group, amines are classified according to their degree of substitution at nitrogen. An amine with one carbon attached to nitrogen is a primary amine, an amine with two is a secondary amine, and an amine with three is a tertiary amine. The groups attached to nitrogen may be any combination of alkyl or aryl groups. Amines are named in two main ways, in the IUPAC system: either as alkylamines or as alkanamines. When primary amines are named as alkylamines, the ending -amine is added to the name of the alkyl group that bears the nitrogen. When named as alkanamines, the alkyl group is named as an alkane and the -e ending replaced by -amine. PROBLEM 22.1 Give an acceptable alkylamine or alkanamine name for each of the following amines: (a) C6H5CH2CH2NH2 (b) (c) CH2œCHCH2NH2 SAMPLE SOLUTION (a) The amino substituent is bonded to an ethyl group that bears a phenyl substituent at C-2. The compound C6H5CH2CH2NH2 may be named as either 2-phenylethylamine or 2-phenylethanamine. Aniline is the parent IUPAC name for amino-substituted derivatives of benzene. Substituted derivatives of aniline are numbered beginning at the carbon that bears the amino group. Substituents are listed in alphabetical order, and the direction of numbering is governed by the usual “first point of difference” rule. Arylamines may also be named as arenamines. Thus, benzenamine is an alternative, but rarely used, name for aniline. F 4 NH2 1 p-Fluoroaniline NH2 Br CH2CH3 5 1 2 5-Bromo-2-ethylaniline C6H5CHNH2 CH3 CH3CH2NH2 Ethylamine (ethanamine) NH2 Cyclohexylamine (cyclohexanamine) CH3CHCH2CH2CH3 NH2 1-Methylbutylamine (2-pentanamine) R N H H Primary amine N R H R Secondary amine N R R R Tertiary amine 22.1 Amine Nomenclature 859 Aniline was first isolated in 1826 as a degradation product of indigo, a dark blue dye obtained from the West Indian plant Indigofera anil, from which the name aniline is derived. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-TWo Amines Compounds with two amino groups are named by adding the suffix -diamine to the name of the corresponding alkane or arene. The final -e of the parent hydrocarbon H2NCH, CHCH3 H, CH, CH2CH, CH,CH,, H,N 1. 6-Hexanediamine 14-Benzenediamine for a. Amino groups rank rather low in seniority when the parent compound is identified naming purposes. Hydroxyl and carbonyl groups outrank amino groups. In these cases, the amino group is as a substituent HOCH, CHNH NH2 (4-Aminobenzenecarbaldehyde) Secondary and tertiary amines are named as N-substituted derivatives of primary mines.The parent primary amine is taken to be the one with the longest carbon chain. The prefix N- is added as a locant to identify substituents on the amino nitrogen as NHCH,CH3 N(CH3h2 CHANHCHCH N-Methylethylamine 4-Chloro-N-ethyl-3- N, N-Dimethylcyclo- nitroaniline (a secondary amine) (a secondary amine) (a tertiary amine) TPROBLEM 22.2 Assign alkanamine names to N-methylethylamine and to N, N- methylcycloheptylamine SAMPLE SOLUTION N-Methylethylamine (given as CH3NHCH2 CH3 in the pre ceding example)is an N-substituted derivative of ethanamine; it is N- PROBLEM 22.3 Classify the following amine as primary, secondary, or tertiary, and give it an acceptable IUPAC nam CH)2CH→ CHCH A nitrogen that bears four substituents is positively charged and is named as an ammonium ion. The anion that is associated with it is also identified in the name Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Compounds with two amino groups are named by adding the suffix -diamine to the name of the corresponding alkane or arene. The final -e of the parent hydrocarbon is retained. Amino groups rank rather low in seniority when the parent compound is identified for naming purposes. Hydroxyl groups and carbonyl groups outrank amino groups. In these cases, the amino group is named as a substituent. Secondary and tertiary amines are named as N-substituted derivatives of primary amines. The parent primary amine is taken to be the one with the longest carbon chain. The prefix N- is added as a locant to identify substituents on the amino nitrogen as needed. PROBLEM 22.2 Assign alkanamine names to N-methylethylamine and to N,Ndimethylcycloheptylamine. SAMPLE SOLUTION N-Methylethylamine (given as CH3NHCH2CH3 in the preceding example) is an N-substituted derivative of ethanamine; it is Nmethylethanamine. PROBLEM 22.3 Classify the following amine as primary, secondary, or tertiary, and give it an acceptable IUPAC name. A nitrogen that bears four substituents is positively charged and is named as an ammonium ion. The anion that is associated with it is also identified in the name. (CH3)2CH N CH2CH3 CH3 CH3NHCH2CH3 N-Methylethylamine (a secondary amine) NO2 Cl 4 1 3 NHCH2CH3 4-Chloro-N-ethyl-3- nitroaniline (a secondary amine) N(CH3)2 N,N-Dimethylcycloheptylamine (a tertiary amine) HOCH2CH2NH2 2-Aminoethanol HC NH2 O 1 4 p-Aminobenzaldehyde (4-Aminobenzenecarbaldehyde) H2NCH2CHCH3 NH2 1,2-Propanediamine H2NCH2CH2CH2CH2CH2CH2NH2 1,6-Hexanediamine H2N NH2 1,4-Benzenediamine 860 CHAPTER TWENTY-TWO Amines Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
22.2 Structure and Bonding 861 47 ppm GURE 22.1A ball- and-stick model of methyl- pyramidal arrangement of stable conformation has the staggered arrangement of bonds shown. Other alkyl- CH CHINH2 CI chacha cfco CHS CH,N(CH3)3 I Methylammonium N-Ethyl-N-methylcyclopentyl Benzyltrimethyl chloride ammonium trifluoroacetate ammonium iodide Ammonium salts that have four alkyl groups bonded to nitrogen are called quaternary ammonium salts 22.2 STRUCTURE AND BONDING Alkylamines: As shown in Figure 22 1 methylamine, like ammonia, has a pyramidal arrangement of bonds to nitrogen. Its H-N-H angles(106)are slightly smaller than the tetrahedral value of 109.5, whereas the C-N-H angle (112 )is slightly larger The C-N bond distance of 147 pm lies between typical C-C bond distances in alkanes (153 pm)and C-O bond distances in alcohols(143 pm) An orbital hybridization description of bonding in methylamine is shown in Fig- ure 22.2. Nitrogen and carbon are both sp-hybridized and are joined by a o bond. The FIGURE 22.2 Orbital hybridization description of bonding in methylamine. (a)Carbon has four valence electrons; each of four equivalent sp-hybridized orbitals contains one electron Nitrogen has five valence electrons. Three of its sp hybrid orbitals contain one electron each; the fourth sp hybrid orbital contains two electrons. (b)Nitrogen and carbon are connected by a o bond in methylamine. This o bond is formed by overlap of an sp hybrid orbital on each atom. the five hy drogen atoms of methylamine are joined to carbon and nitrogen by o bonds. The two remaining electrons of nitrogen occupy an sp-hybridized orbital Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Ammonium salts that have four alkyl groups bonded to nitrogen are called quaternary ammonium salts. 22.2 STRUCTURE AND BONDING Alkylamines: As shown in Figure 22.1 methylamine, like ammonia, has a pyramidal arrangement of bonds to nitrogen. Its H±N±H angles (106°) are slightly smaller than the tetrahedral value of 109.5°, whereas the C±N±H angle (112°) is slightly larger. The C±N bond distance of 147 pm lies between typical C±C bond distances in alkanes (153 pm) and C±O bond distances in alcohols (143 pm). An orbital hybridization description of bonding in methylamine is shown in Figure 22.2. Nitrogen and carbon are both sp3 -hybridized and are joined by a bond. The CH3NH3 Cl Methylammonium chloride NCH2CH3 CH3 H CF3CO2 N-Ethyl-N-methylcyclopentylammonium trifluoroacetate C6H5CH2N(CH3)3 I Benzyltrimethylammonium iodide (a quaternary ammonium salt) 22.2 Structure and Bonding 861 147 ppm 112 106 C N H H H H H (a) (b) FIGURE 22.1 A balland-stick model of methylamine showing the trigonal pyramidal arrangement of bonds to nitrogen. The most stable conformation has the staggered arrangement of bonds shown. Other alkylamines have similar geometries. FIGURE 22.2 Orbital hybridization description of bonding in methylamine. (a) Carbon has four valence electrons; each of four equivalent sp3 -hybridized orbitals contains one electron. Nitrogen has five valence electrons. Three of its sp3 hybrid orbitals contain one electron each; the fourth sp3 hybrid orbital contains two electrons. (b) Nitrogen and carbon are connected by a bond in methylamine. This bond is formed by overlap of an sp3 hybrid orbital on each atom. The five hydrogen atoms of methylamine are joined to carbon and nitrogen by bonds. The two remaining electrons of nitrogen occupy an sp3 -hybridized orbital. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-TWo Amines unshared electron pair on nitrogen occupies an sp-hybridized orbital. This lone pair is involved in reactions in which amines act as bases or nucleophiles. The graphic that You can opened this chapter is an electrostatic potential map that clearly shows the concentration cluding its electros of electron density at nitrogen in methylamine tial, in more detail By Modeling Arylamines: Aniline, like alkylamines, has a pyramidal arrangement of bonds around nitrogen, but its pyramid is somewhat shallower. One measure of the extent of this flat tening is given by the angle between the carbon-nitrogen bond and the bisector of the l80° Methylamine O=cHNH) For sp-hybridized nitrogen, this angle(not the same as the c-N--H bond angle)is 125, and the measured angles in simple alkylamines are close to that. The correspond ing angle for sp- hybridization at nitrogen with a planar arrangement of bonds, as in amines is discussed in an arti. amides, for example, is 180. The measured value for this angle in aniline is 142.5, sug cle entitled "What Is the gesting a hybridization somewhat closer to sp than to sp Geometry at Trigonal Nitro. gen?in the January 1998 is- The structure of aniline reflects a compromise between two modes of binding the nitrogen lone pair(Figure 22.3). The electrons are more strongly attracted to nitrogen Chemical Education, pp when they are in an orbital with some s character--an sp-hybridized orbital, for exam- ple--than when they are in a p orbital. On the other hand, delocalization of these elec trons into the aromatic T system is better achieved if they occupy a p orbital. A p orbital of nitrogen is better aligned for overlap with the p orbitals of the benzene ring to form a) FIGURE 22. 3 Electrostatic potential maps of the aniline in which the geometry at nitrogen is(a)nonplanar and(b)planar. In the nonplanar geometry, the unshared pair occupies an brid orbital of nitrogen. The region of highest In the planar geometry, nitrogen is sp 2-hybridize the electron pair is delocalized between p orbital of nitrogen and the t system of the he region of highest electron density in( b) encompasses both the ring and nitrogen the actual structure combines features of both; nitro- n adopts a hybridization state between sp and Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
unshared electron pair on nitrogen occupies an sp3 -hybridized orbital. This lone pair is involved in reactions in which amines act as bases or nucleophiles. The graphic that opened this chapter is an electrostatic potential map that clearly shows the concentration of electron density at nitrogen in methylamine. Arylamines: Aniline, like alkylamines, has a pyramidal arrangement of bonds around nitrogen, but its pyramid is somewhat shallower. One measure of the extent of this flattening is given by the angle between the carbon–nitrogen bond and the bisector of the H±N±H angle. For sp3 -hybridized nitrogen, this angle (not the same as the C±N±H bond angle) is 125°, and the measured angles in simple alkylamines are close to that. The corresponding angle for sp2 hybridization at nitrogen with a planar arrangement of bonds, as in amides, for example, is 180°. The measured value for this angle in aniline is 142.5°, suggesting a hybridization somewhat closer to sp3 than to sp2 . The structure of aniline reflects a compromise between two modes of binding the nitrogen lone pair (Figure 22.3). The electrons are more strongly attracted to nitrogen when they are in an orbital with some s character—an sp3 -hybridized orbital, for example—than when they are in a p orbital. On the other hand, delocalization of these electrons into the aromatic system is better achieved if they occupy a p orbital. A p orbital of nitrogen is better aligned for overlap with the p orbitals of the benzene ring to form ≈125 Methylamine (CH3NH2) Aniline (C6H5NH2) Formamide (OœCHNH2) 142.5 180 862 CHAPTER TWENTY-TWO Amines The geometry at nitrogen in amines is discussed in an article entitled “What Is the Geometry at Trigonal Nitrogen?” in the January 1998 issue of the Journal of Chemical Education, pp. 108–109. (a) (b) FIGURE 22.3 Electrostatic potential maps of the aniline in which the geometry at nitrogen is (a) nonplanar and (b) planar. In the nonplanar geometry, the unshared pair occupies an sp3 hybrid orbital of nitrogen. The region of highest electron density in (a) is associated with nitrogen. In the planar geometry, nitrogen is sp2 -hybridized and the electron pair is delocalized between a p orbital of nitrogen and the system of the ring. The region of highest electron density in (b) encompasses both the ring and nitrogen. The actual structure combines features of both; nitrogen adopts a hybridization state between sp3 and sp2 . You can examine the structure of methylamine, including its electrostatic potential, in more detail on Learning By Modeling. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
22.3 Physical Properties an extended T system than is an sp-hybridized orbital. As a result of these two oppos- ing forces, nitrogen adopts an orbital hybridization that is between sp' and sp The corresponding resonance description shows the delocalization of the nitrogen lone-pair electrons in terms of contributions from dipolar structures NH2 NH2 NH2 JHa H < H H Lewis structure The orbital and resonance models for bonding in arylamines are simply alternative ways of describing the same phenomenon. Delocalization of the nitrogen lone pair decreases the electron density at nitrogen while increasing it in the Tr system of the aro- matic ring. Weve already seen one chemical consequence of this in the high level of reactivity of aniline in electrophilic aromatic substitution reactions( Section 12. 12). Other ways in which electron delocalization affects the properties of arylamines are described in later sections of this chapter PROBLEM 22. 4 As the extent of electron delocalization into the ring increases the geometry at nitrogen flattens p-Nitroaniline, for example, is planar write a resonance form for p-nitroaniline that shows how the nitro group increases elec- tron delocalization. Examine the electrostatic potential of the p-nitroaniline model on Learning By Modeling. Where is the greatest concentration of negative charge 22.3 PHYSICAL PROPERTIES We have often seen that the polar nature of a substance can affect physical properties such as boiling point. This is true for amines, which are more polar than alkanes but less polar than alcohols. For similarly constituted compounds, alkylamines have boiling points higher than those of alkanes but lower than those of alcohols ollection of physical prop- CH3CH,CH3 CH3 CH2NH, CH3 CH,OH Propane Ethylamine Ethanol OD u=1.7D ith unpleasant,“ fishy bp-42°C bp 17C bp78°C Dipole-dipole interactions, especially hydrogen bonding, are present in amines but absent in alkanes. The less polar nature of amines as compared with alcohols, however, makes these intermolecular forces weaker in amines than in alcohols Among isomeric amines, primary amines have the highest boiling points, and ter- tiary amines the lowest CH3 CH,CH,NH CH=,NHCH3 (CH3)3N (a primary amin a tertiary amine) bps0°c bp3° Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
an extended system than is an sp3 -hybridized orbital. As a result of these two opposing forces, nitrogen adopts an orbital hybridization that is between sp3 and sp2 . The corresponding resonance description shows the delocalization of the nitrogen lone-pair electrons in terms of contributions from dipolar structures. The orbital and resonance models for bonding in arylamines are simply alternative ways of describing the same phenomenon. Delocalization of the nitrogen lone pair decreases the electron density at nitrogen while increasing it in the system of the aromatic ring. We’ve already seen one chemical consequence of this in the high level of reactivity of aniline in electrophilic aromatic substitution reactions (Section 12.12). Other ways in which electron delocalization affects the properties of arylamines are described in later sections of this chapter. PROBLEM 22.4 As the extent of electron delocalization into the ring increases, the geometry at nitrogen flattens. p-Nitroaniline, for example, is planar. Write a resonance form for p-nitroaniline that shows how the nitro group increases electron delocalization. Examine the electrostatic potential of the p-nitroaniline model on Learning By Modeling. Where is the greatest concentration of negative charge? 22.3 PHYSICAL PROPERTIES We have often seen that the polar nature of a substance can affect physical properties such as boiling point. This is true for amines, which are more polar than alkanes but less polar than alcohols. For similarly constituted compounds, alkylamines have boiling points higher than those of alkanes but lower than those of alcohols. Dipole–dipole interactions, especially hydrogen bonding, are present in amines but absent in alkanes. The less polar nature of amines as compared with alcohols, however, makes these intermolecular forces weaker in amines than in alcohols. Among isomeric amines, primary amines have the highest boiling points, and tertiary amines the lowest. CH3CH2CH2NH2 Propylamine (a primary amine) bp 50°C CH3CH2NHCH3 N-Methylethylamine (a secondary amine) bp 34°C (CH3)3N Trimethylamine (a tertiary amine) bp 3°C CH3CH2CH3 Propane 0 D bp 42°C CH3CH2NH2 Ethylamine 1.2 D bp 17°C CH3CH2OH Ethanol 1.7 D bp 78°C H H H H H NH2 Most stable Lewis structure for aniline H H H H H NH2 H H H H H NH2 H H H H H NH2 Dipolar resonance forms of aniline 22.3 Physical Properties 863 A collection of physical properties of some representative amines is given in Appendix 1. Most commonly encountered alkylamines are liquids with unpleasant, “fishy” odors. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-TWo Amines Primary and secondary amines can participate in intermolecular hydrogen bonding, but tertiary amines cannot. Amines that have fewer than six or seven carbon atoms are soluble in water. all amines, even tertiary amines, can act as proton acceptors in hydrogen bonding to water molecules The simplest arylamine, aniline, is a liquid at room temperature and has a boiling point of 184C. Almost all other arylamines have higher boiling points. Aniline is only slightly soluble in water (3 g/100 mL) Substituted derivatives of aniline tend to be even 22.4 MEASURES OF AMINE BASICITY Two conventions are used to measure the basicity of amines. One of them defines a basicity constant Kb for the amine acting as a proton acceptor from water: RN: /+H-OH RN—H+:OH IR3NHTJHO IR,N and pkb =-log Kb For ammonia, Kb=1.8 10(pKb=4.7). A typical amine such as methylamine (CH3 NH2) is a stronger base than ammonia and has Kb =4.4 X 10(pKb=3.3) The other convention relates the basicity of an amine(r3N) to the acid dissocic tion constant Ka of its conjugate acid(r3NH R N-HFH++R,N where Ka and pKa have their usual meaning HR,N RNH’] log Ka The conjugate acid of ammonia is ammonium ion(NH), which has K=5.6X 10- (pKa=9.3). The conjugate acid of methylamine is methylammonium ion(CH3NH3) which has Ka=2 X 10(pKa =10.7). The more basic the amine, the weaker is its conjugate acid Methy lamine is a stronger base than ammonia; methylammonium ion is a weaker acid than ammonium ion The relationship between the equilibrium constant Kb for an amine(R3N)and Ka KnKb =10 and pka t pkb= 14 PROBLEM 22.5 A chemistry handbook lists Kb for quinine as 1 x 10. What is pk for quinine? What are the values of Ka and pka for the conjugate acid of qui nine Citing amine basicity according to the acidity of the conjugate acid permits acid-base reactions involving amines to be analyzed according to the usual Bronsted relationships. By comparing the acidity of an acid with the conjugate acid of an amine, for example, we see that amines are converted to ammonium ions by acids even as weak as acetic acid Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Primary and secondary amines can participate in intermolecular hydrogen bonding, but tertiary amines cannot. Amines that have fewer than six or seven carbon atoms are soluble in water. All amines, even tertiary amines, can act as proton acceptors in hydrogen bonding to water molecules. The simplest arylamine, aniline, is a liquid at room temperature and has a boiling point of 184°C. Almost all other arylamines have higher boiling points. Aniline is only slightly soluble in water (3 g/100 mL). Substituted derivatives of aniline tend to be even less water-soluble. 22.4 MEASURES OF AMINE BASICITY Two conventions are used to measure the basicity of amines. One of them defines a basicity constant Kb for the amine acting as a proton acceptor from water: Kb and pKb log Kb For ammonia, Kb 1.8 105 (pKb 4.7). A typical amine such as methylamine (CH3NH2) is a stronger base than ammonia and has Kb 4.4 104 (pKb 3.3). The other convention relates the basicity of an amine (R3N) to the acid dissociation constant Ka of its conjugate acid (R3NH): where Ka and pKa have their usual meaning: Ka and pKa log Ka The conjugate acid of ammonia is ammonium ion (NH4 ), which has Ka 5.6 1010 (pKa 9.3). The conjugate acid of methylamine is methylammonium ion (CH3NH3 ), which has Ka 2 1011 (pKa 10.7). The more basic the amine, the weaker is its conjugate acid. Methylamine is a stronger base than ammonia; methylammonium ion is a weaker acid than ammonium ion. The relationship between the equilibrium constant Kb for an amine (R3N) and Ka for its conjugate acid (R3NH) is: KaKb 1014 and pKa pKb 14 PROBLEM 22.5 A chemistry handbook lists Kb for quinine as 1 106 . What is pKb for quinine? What are the values of Ka and pKa for the conjugate acid of quinine? Citing amine basicity according to the acidity of the conjugate acid permits acid–base reactions involving amines to be analyzed according to the usual Brønsted relationships. By comparing the acidity of an acid with the conjugate acid of an amine, for example, we see that amines are converted to ammonium ions by acids even as weak as acetic acid: [H][R3N] [R3NH] R3N H R3N H [R3NH][HO] [R3N] R3N H OH R3N H OH 864 CHAPTER TWENTY-TWO Amines Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
22.5 Basicity of Amines Recall from Section 4.6 that acid-base reactions are char. H—OCCH3 OCCH cterized by equilibrium con Methylamine Acetate the left side of the equation (stronger acid; pKa= 4.7) eaker acid; pK=10.7) ind the weaker acid on the Conversely, adding sodium hydroxide to an ammonium salt converts it to the free CH →CH3NH2+ H-OH Methylammor Hydroxide ion Methylamine (stronger acid; pKa =10.7) ply the Henderson-Hasselbalch equation (see"Quantitative Relationships Involving Carboxylic Acids, the box accompanying Section 19.4)to calculate the CHaNH3 T/CH3 NH, ratio in water buffered at pH 7. Their basicity provides a means by which amines may be separated from neutral organic compounds. A mixture containing an amine is dissolved in diethyl ether and shaken with dilute hydrochloric acid to convert the amine to an ammonium salt. The ammonium salt, being ionic, dissolves in the aqueous phase, which is separated from the ether layer. Adding sodium hydroxide to the aqueous layer converts the ammonium salt back to the free amine, which is then removed from the aqueous phase by extraction with a fresh portion of ether. 22.5 BASICITY OF AMINES Amines are weak bases, but as a class, amines are the strongest bases of all neutral mol- ecules. Table 22 1 lists basicity data for a number of amines. The most important rela- tionships to be drawn from the data are 1. Alkylamines are slightly stronger bases than ammonia. 2. Alkylamines differ very little among themselves in basicity. Their basicities cover a range of less than 10 in equilibrium constant (1 pK unit). 3. Arylamines are much weaker bases than ammonia and alkylamines. Their basicity constants are on the order of 10 smaller than those of alkylamines(6 pK units) The differences in basicity between ammonia, and primary, secondary, and tertiary alkylamines result from the interplay between steric and electronic effects on the mole- cules themselves and on the solvation of their conjugate acids. In total, the effects are mall, and most alkylamines are very similar in basicity Arylamines are a different story, however; most are about a million times weaker as bases than ammonia and alkylamines As unfavorable as the equilibrium is for cyclohexylamine acting as a base in nh h,o NH3 HO (Kb44×10;pKb3.4) Cyclohexylamine Water Cyclohexylammonium Hydroxide Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Conversely, adding sodium hydroxide to an ammonium salt converts it to the free amine: PROBLEM 22.6 Apply the Henderson–Hasselbalch equation (see “Quantitative Relationships Involving Carboxylic Acids,” the box accompanying Section 19.4) to calculate the CH3NH3 /CH3NH2 ratio in water buffered at pH 7. Their basicity provides a means by which amines may be separated from neutral organic compounds. A mixture containing an amine is dissolved in diethyl ether and shaken with dilute hydrochloric acid to convert the amine to an ammonium salt. The ammonium salt, being ionic, dissolves in the aqueous phase, which is separated from the ether layer. Adding sodium hydroxide to the aqueous layer converts the ammonium salt back to the free amine, which is then removed from the aqueous phase by extraction with a fresh portion of ether. 22.5 BASICITY OF AMINES Amines are weak bases, but as a class, amines are the strongest bases of all neutral molecules. Table 22.1 lists basicity data for a number of amines. The most important relationships to be drawn from the data are 1. Alkylamines are slightly stronger bases than ammonia. 2. Alkylamines differ very little among themselves in basicity. Their basicities cover a range of less than 10 in equilibrium constant (1 pK unit). 3. Arylamines are much weaker bases than ammonia and alkylamines. Their basicity constants are on the order of 106 smaller than those of alkylamines (6 pK units). The differences in basicity between ammonia, and primary, secondary, and tertiary alkylamines result from the interplay between steric and electronic effects on the molecules themselves and on the solvation of their conjugate acids. In total, the effects are small, and most alkylamines are very similar in basicity. Arylamines are a different story, however; most are about a million times weaker as bases than ammonia and alkylamines. As unfavorable as the equilibrium is for cyclohexylamine acting as a base in water, CH3N H H H Methylammonium ion (stronger acid; pKa 10.7) OH Hydroxide ion CH3NH2 Methylamine H OH Water (weaker acid; pKa 15.7) CH3NH2 Methylamine H OCCH3 O Acetic acid (stronger acid; pKa 4.7) CH3NH3 Methylammonium ion (weaker acid; pKa 10.7) OCCH3 O Acetate ion 22.5 Basicity of Amines 865 NH2 Cyclohexylamine H2O Water NH3 Cyclohexylammonium ion HO Hydroxide ion (Kb 4.4 104 ; pKb 3.4) Recall from Section 4.6 that acid–base reactions are characterized by equilibrium constants greater than unity when the stronger acid is on the left side of the equation and the weaker acid on the right. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-TWo Amines TABLE 22.1 Base Strength of Amines As Measured by Their Basicity Constants and the Dissociation Basic Acidity of conjugate acid Compound Structure 1.8×10-5 5.5×10-10 4.4×10 2.3×10-11 10.6 Ethylamine 5.6×10 1.8×10 sopropylamine 4.3×10-4 2.3 10.6 tert-Butylamine (CH3)3CNH2 2.8×10-4 3.6 3.6×10 10.4 Aniline 3.8×10-10 2.6×10 Secondary amines Dimethylamine 5.1×10-4 2.0×10-1 10 Diethylamine (CH3 CH2)2NH 1.3×10-3 7.7×10-1 N-Methylaniline HsNHCH 6.1×10-10 1.6×10-5 Tertiary amines amine CHaN 5.3×10-5 4.3 1.9×10-10 Triethylamine (CH3 CH2)3N 5.6×10-4 1.8×10 N, N-Dimethylaniline CHsN(CH3)2 1.2×10-9 8.9 8.3×10 *In water at25°C it is far less favorable for aniline Ha HO NHa Ho (K3.8×10-10;pk94) Anilinium ion Hydroxid lamine and aniline on Learning Aniline is a much weaker base because its delocalized lone pair is more strongly held than the nitrogen lone pair in cyclohexylamine. The more strongly held the electron pair, the less able it is to abstract a proton +hop HO M Aniline is stabilized by delocalization of lone pair into T system of ring, decreasing the electron When the proton donor is a strong acid, arylamines can be completely protor Aniline is extracted from an ether solution into 1 M hydrochloric acid because it is erted to a water-soluble anilinium ion salt under these condition Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
it is far less favorable for aniline. Aniline is a much weaker base because its delocalized lone pair is more strongly held than the nitrogen lone pair in cyclohexylamine. The more strongly held the electron pair, the less able it is to abstract a proton. When the proton donor is a strong acid, arylamines can be completely protonated. Aniline is extracted from an ether solution into 1 M hydrochloric acid because it is converted to a water-soluble anilinium ion salt under these conditions. N H H Aniline is stabilized by delocalization of lone pair into system of ring, decreasing the electron density at nitrogen. H2O N H H H HO 866 CHAPTER TWENTY-TWO Amines TABLE 22.1 Base Strength of Amines As Measured by Their Basicity Constants and the Dissociation Constants of Their Conjugate Acids* Compound *In water at 25°C. Ammonia Primary amines Methylamine Ethylamine Isopropylamine tert-Butylamine Aniline Secondary amines Dimethylamine Diethylamine N-Methylaniline Kb 1.8 105 4.4 104 5.6 104 4.3 104 2.8 104 3.8 1010 5.1 104 1.3 103 6.1 1010 5.3 105 5.6 104 1.2 109 pKb 4.7 3.4 3.2 3.4 3.6 9.4 3.3 2.9 9.2 4.3 3.2 8.9 Ka 5.5 1010 2.3 1011 1.8 1011 2.3 1011 3.6 1011 2.6 105 2.0 1011 7.7 1012 1.6 105 1.9 1010 1.8 1011 8.3 106 pKa 9.3 10.6 10.8 10.6 10.4 4.6 10.7 11.1 4.8 9.7 10.8 5.1 Structure NH3 CH3NH2 CH3CH2NH2 (CH3)2CHNH2 (CH3)3CNH2 C6H5NH2 (CH3)2NH (CH3CH2)2NH C6H5NHCH3 (CH3)3N (CH3CH2)3N C6H5N(CH3)2 Tertiary amines Trimethylamine Triethylamine N,N-Dimethylaniline Basicity Acidity of conjugate acid NH2 Aniline H2O Water NH3 Anilinium ion HO Hydroxide ion (Kb 3.8 1010; pKb 9.4) Compare the calculated charge on nitrogen in cyclohexylamine and aniline on Learning By Modeling. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
22.5 Basicity of Amines PROBLEM 22. 7 The two amines a factor of 40.000 in their values. Which is the stronger base heir structures on Learning 6 Modeling. What are the calculated ne two nitro Tetrahydroquinoline Tetrahydroisoquinoline Conjugation of the amino group of an arylamine with a second aromatic ring, then a third, reduces its basicity even further. Diphenylamine is 6300 times less basic than aniline, whereas triphenylamine is scarcely a base at all, being estimated as 10 times less basic than aniline and 10 4 times less basic than ammonia. C6HSNH3 (ChS)2NH (C6H5)3N Aniline Diphenyl Triphenylamine (Kb3.8×10-10;(K16×1 pKb.4) pKb =19) In general, electron-donating substituents on the aromatic ring increase the basic ity of arylamines slightly. Thus, as shown in Table 22.2, an electron-donating methyl group in the para position increases the basicity of aniline by a factor of only 5-6 (less than I pk unit). Electron-withdrawing groups are base-weakening and exert larger effects. A p-trifluoromethyl group decreases the basicity of aniline by a factor of 200 ind a p-nitro group by a factor of 3800. In the case of p-nitroaniline a resonance inter action of the type shown provides for extensive delocalization of the unshared electron pair of the amine grou Just as aniline is much less basic than alkylamines because the unshared electron pair of nitrogen is delocalized into the T system of the ring, p-nitroaniline is even less basic because the extent of this delocalization is greater and involves the oxygens of the nitro TABLE 22.2 Effect of Substituents on the Basicity of Aniline H 4×10 9.4 CHa 2×10 8.7 2×10-12 11.5 O2N 1×10-13 13.0 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 22.7 The two amines shown differ by a factor of 40,000 in their Kb values. Which is the stronger base? Why? View their structures on Learning By Modeling. What are the calculated charges on the two nitrogens? Conjugation of the amino group of an arylamine with a second aromatic ring, then a third, reduces its basicity even further. Diphenylamine is 6300 times less basic than aniline, whereas triphenylamine is scarcely a base at all, being estimated as 108 times less basic than aniline and 1014 times less basic than ammonia. In general, electron-donating substituents on the aromatic ring increase the basicity of arylamines slightly. Thus, as shown in Table 22.2, an electron-donating methyl group in the para position increases the basicity of aniline by a factor of only 5–6 (less than 1 pK unit). Electron-withdrawing groups are base-weakening and exert larger effects. A p-trifluoromethyl group decreases the basicity of aniline by a factor of 200 and a p-nitro group by a factor of 3800. In the case of p-nitroaniline a resonance interaction of the type shown provides for extensive delocalization of the unshared electron pair of the amine group. Just as aniline is much less basic than alkylamines because the unshared electron pair of nitrogen is delocalized into the system of the ring, p-nitroaniline is even less basic because the extent of this delocalization is greater and involves the oxygens of the nitro group. N NH2 O O N NH2 O O Electron delocalization in p-nitroaniline C6H5NH2 Aniline (Kb 3.8 1010; pKb 9.4) (C6H5)2NH Diphenylamine (Kb 6 1014; pKb 13.2) (C6H5)3N Triphenylamine (Kb 1019; pKb 19) N H Tetrahydroquinoline NH Tetrahydroisoquinoline 22.5 Basicity of Amines 867 TABLE 22.2 Effect of Substituents on the Basicity of Aniline X H CH3 CF3 O2N 4 1010 2 109 2 1012 1 1013 Kb 9.4 8.7 11.5 13.0 pKb X NH2 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
