Ozone reacts with aliphatic amines and amino acids by adding to the lone pair at nitrogen [reaction (1)].
N R R
R (1) N
R R
R
O O O O3
Ammonia, the parent of the amines, reacts only very slowly with ozone (Table 8.1; for a catalysis by Br− see Chapter 11). Alkylamines react several orders of magnitude faster. Electron-donating alkyl groups
pH
log k
pK5 = 6.2 pK6 = 10.2
4 6 8 10
3 4 5 6
Figure 8.2 Logarithm of the ozone rate constant of ethylenediaminetetraacetic acid (EDTA) as a function of pH according to Muñoz & von Sonntag, 2000b, with permission. For structure of EDTA see Section 8.3.
enhance the electron density at nitrogen allowing the electrophilic ozone to undergo the addition reaction (1) more readily. This increase in electron density can be seen from the dependence of the HOMO as a function of the number of alkyl substituents (Figure 8.3).
An increase in the electron density at nitrogen should correlate with a decrease of the standard Gibbs free energy of reaction (1), and it would be tempting to correlate the rate constants of the reaction of ozone with the standard Gibbs free energy of adduct formation, reaction (1), as has been successfully done in the case of the addition of ozone to aromatic compounds (Chapter 7). A major problem in arriving at reliable data is, however, the fact that a water molecule hydrogen bonded to the nitrogen is replaced by ozone and the loss of this hydrogen bond (ca. 25 kJ mol−1) may have to be taken into account (note that this problem does not arise with aromatic compounds, Chapter 7). Moreover, steric effects seem to play an important role. This is apparent from the drop in the pKa value on going from the (protonated) dimethylamine (pKa=10.64) to trimethylamine (pKa=9.8) despite the fact that the nitrogen in trimethylamine has a higher electron density (Figure 8.3).
The ozone adducts to amines may lose O2[reaction (2)].
N R R
R
O O O
(2) N
R R
R
O + 1O2
Since the ozone adduct in its ground state is in its singlet state, the overall spin multiplicity of the products must also be a singlet (spin conservation rule). As a consequence, O2is released in its (excited) singlet state [1O2, O2(1Δg)], which lies 95.5 kJ mol−1above the (triplet) ground state of O2[3O2, O2(3Σg–)]. The singlet oxygen yields in ozone reactions are typically high (Table 8.2).
With tertiary amines, this reaction results in the formation ofN-oxides [reaction (2)] (Muñoz & von Sonntag, 2000b; Lange et al., 2006; Zimmermann et al., 2012) (Table 8.3). For trimethylamine,
0 1 2 3
–8.0 –7.5 –7.0 –6.5 –6.0
EtNH2 MeNH2
Et2NH
Me3N Et3N
Me2NH
NH3
HOMO / eV
Number of methyl (ethyl) substituents
Figure 8.3 Energy of the HOMO of ammonia and its methyl and ethyl derivatives vs. the number of methyl (ethyl) substituents (Naumov & von Sonntag, 2009, unpublished).
quantum-chemical calculations indicate that reactions (1) and (2) are both exergonic [ΔG0= −48 kJ mol−1 and−63 kJ mol−1, respectively; Naumov & von Sonntag (2010, unpublished)].
Detailed data on primary and secondary amines are not yet available, but for dimethylamine quantum-chemical calculations indicate that reactions (1) and (2) are also both exergonic (ΔG0=
−41 kJ mol−1and−74 kJ mol−1, respectively) and that the correspondingN-oxide is only a short-lived Table 8.2 Singlet oxygen (1O2) yields (in mol % of mol ozone consumed) in the reaction of
ozone with amines at different pH values. The ratio of substrate concentration to ozone concentration is given in parentheses. According to Muñozet al.(2001)
Substrate pH 1O2yield/% ([substrate] : [ozone])
Trimethylamine 7 63 (10:1)
9.5 60 (10:1), 69 (100:1)
Triethylamine 7 No signal (1:1), 42 (10:1), 72 (10:1)
8 No signal (1:1), 63 (10:1), 80 (100:1) 9.5 52 (1:1), 73 (10:1), 85 (100:1)
10.5 59 (1:1)
11.5 78 (100:1)
DABCO 7 70 (1:1), 80 (10:1)
9 90 (10:1)
Ethylenediaminetetraacetic acid (EDTA)
4.5 No signal (1:1), 19 (10:1)
5.5 No signal (1:1), 40 (10:1), 39 (100:1) 7 39 (1:1), 59 (10:1), 43 (100:1) 9.5 31 (1:1), 33 (10:1), 37 (100:1)
EDTA/Ca2+ ∼3 15 (10:1)
EDTA/Fe3+ ∼3 No signal (1:1), No signal (10:1)
Nitrilotriacetic acid (NTA) 7 No signal (1:1), 18 (10:1) 9.5 22 (1:1), 21 (10:1)
Diethylamine 9 20 (1:1)
10.5 24 (1:1), 20 (10:1)
Iminodiacetic acid (IDA) 9 17 (1:1)
10.5 20 (1:1), 18 (10:1)
Ethylamine 9 No signal (1:1)
10.5 11 (1:1), 17 (10:1)
Glycine 7 No signal (1:1), (10:1)
10.5 4 (10:1)
N,N-Diethylaniline 8.5 7 (17:1)
N,N,N′,N′ -Tetramethyl-phenylenediamine
3.5 9 (3:1)
6 4 (3:1)
intermediate and rearranges into the isomeric hydroxylamine [reaction (3);ΔG0= −20 kJ mol−1; Naumov
& von Sonntag (2010, unpublished)].
N H R
R
O (3) R N
R OH
In the case of propranolol, the hydroxylamine has been identified (Benner & Ternes, 2009b).
In competition with1O2elimination [reaction (2)], the ozone adduct may also cleave heterolytically, thereby forming an amine radical cation and an ozonide radical anion, O†−3 [reaction (4)]. The latter reacts with water giving rise to†OH [reaction (5), for details see Chapter 11].
N R R
R
O O O
(4) N
R R
R
+ O3
H2O OH + O2 + OH
(5)
In principle, this reaction could also proceed via a direct electron transfer without an adduct as intermediate [reaction (6)].
N R R
R O3
(6) N
R R
R
+ O3
In reactions (4) and (6), two radicals are formed. Whenever two radicals are formed side by side, they are held together by the solvent for a short period of time. If they react with one another at diffusion-controlled rates there is a given chance that they will react within the solvent cage in competition with diffusing out of the cage. The importance of such cage reactions was first addressed by Rabinowitch (Rabinowitch & Wood, 1936; Rabinowitch, 1937). The kinetics for diffusion-controlled reactions were discussed by Noyes (Noyes, 1954). A typical example is the photodecomposition of H2O2. In the gas phase, two†OH are formed per photodissociation event. In water, however, there is a 50% probability of the two †OH formed recombining within the solvent cage to H2O2. Thus in water, the yield of free †OH is only 50% with respect to the primary†OH yield. Viscosity is one parameter that has a substantial effect on the yield of the cage product and so is temperature [for examples of cage effects in free-radical reactions see (Barrett Table 8.3 Products of the reaction of ozone with trimethylamine, triethylamine and 1,4-diazabicyclo[2.2.2]
octane (DABCO) in % of ozone consumed (Muñoz & von Sonntag, 2000b)
Product Trimethylamine Triethylamine DABCO
Aminoxide 93 85 90
Singlet oxygen 69 85 90
Secondary amine Not determined 15 (7)(a) Not observed
Aldehyde 9 19 Not observed
(a)in the presence of tertiary butanol
et al., 1968; Chuanget al., 1974; Market al., 1996; Goldsteinet al., 2005)]. In the given trialkylamine case, this may lead to the formation of theN-oxide [reaction (7)].
N
In contrast to reaction (2), triplet (ground state) O2 can be formed, as radicals have a doublet spin multiplicity, and their disproportionation can lead to one molecule in the singlet state (here: theN-oxide) and one molecule in the triplet state (here: 3O2). This can explain why in the trialkylamines singlet oxygen yields are belowN-oxide yields. Such a gap between the yields of singlet oxygen and O-transfer products is not observed with sulfides, but sulfides do not give rise to free-radicals in their reactions with ozone (Chapter 9).
Besides reactions (4) and (5), †OH radicals can also be formed via O†−2 (O†−2 +O3→O2+O†−3 , cf.
Chapter 13). This ozone-reactive intermediate is formed in the course of the decay of aliphatic amine radical cations [reactions (8)–(11)].
N
Details of the kinetics of reactions (8)–(11), including the rate constants of all individual steps (not shown here), have been elucidated with the help of the pulse radiolysis technique (Das & von Sonntag, 1986; Das et al., 1987) (for a potential role of these reactions in contributing to†OH formation in the reaction of ozone with DOM see Chapter 3). The†OH yields in the reaction of ozone with some amines are compiled in Table 8.4.
Table 8.4 Compilation of†OH yields in % of ozone consumed (mol†OH per mol ozone) in the reaction of ozone with amines
Amine †OH yield/% Reference
Adenosine 43 Flyuntet al., 2003a
Aniline 27 Tekle-Rötteringet al., 2011
Benzotriazole anion ∼32 Lutzeet al., 2011a
Diclofenac 30 Seinet al., 2008
N,N-Diethylaniline 28 Flyuntet al., 2003a
N,N-Diethyl-p-phenylenediamine(a) 23 Jarocki, 2011, unpublished
5,6-Dimethylbenzotriazole anion ∼20 Lutzeet al., 2011a 5-Methylbenzotriazole anion ∼28 Lutzeet al., 2011a
Morpholine 33 Tekle-Rötteringet al., 2011
(Continued)
In the reaction of ozone with activated carbon,†OH radicals are formed (Jans & Hoigné, 1998). This reaction has been attributed to the presence of nitrogen-containing sites in the activated carbon (Sánchez-Poloet al., 2005), and when these sites are oxidised by ozone,•OH production ceases (Chapter 3).
8.2.2 Aromatic amines (anilines)
The reaction of ozone with aniline is very fast (Table 8.1). The rate constant determined by competition with buten-3-ol (k=3.8×107M−1s−1) may still be somewhat too high, because,0.5 mol aniline are destroyed per mol ozone consumed. Aniline shares this phenomenon with diclofenac, and a potential explanation of this has been made below. A rate constant just above 107M−1s−1would be compatible with an addition to the strongly activated aromatic ring [Chapter 7, e.g. reaction (12)], but an addition to the nitrogen must also be envisaged [reactions (13)–(15)].
NH2 O3 (12)
N H
H
O O O NH2
N O3
O3
H O O OH H O O O
(13)
(14) (15)
Quantum-chemical calculations indicate that addition to the ring is markedly exergonic [reaction (12), ΔG0= −53 kJ mol−1, Naumov & von Sonntag (2009, unpublished)]. This value and the above rate constant fall reasonably well on the plot of calculated standard Gibbs free energies vs. the logarithm of the rate constant such as shown in Figure 7.2 (Chapter 7) (Tekle-Röttering et al., 2011). An addition to the nitrogen is slightly endergonic [reaction (13),ΔG0= +15 kJ mol−1]. However, it cannot be excluded that an addition to nitrogen is accompanied with a concomitant proton transfer (in analogy to the well-documented proton transfer coupled electron transfer) [reaction (14),ΔG0= −77 kJ mol−1]. Thus, a reaction at nitrogen, possibly competing with an addition to the ring, is not unlikely.
Table 8.4 Compilation of†OH yields in % of ozone consumed (mol†OH per mol ozone) in the reaction of ozone with amines (Continued)
Amine †OH yield/% Reference
o-Phenylenediamine 30 Flyuntet al., 2003a
N,N,N,N-Tetramethylphenylenediamine 68(b) Flyuntet al., 2003a
Trimethylamine 15 Flyuntet al., 2003a
(a)see Chapter 2,(b)for acaveatsee Flyuntet al. (2003)
Despite the considerable number of papers that deal with the ozone chemistry of aniline (Gilbert &
Zinecker, 1980; Doreet al., 1980; Turhan & Uzman, 2007; Caprio & Insola, 1985), a material balance is still missing. Products that are evidently due to an attack at nitrogen are nitrosobenzene, nitrobenzene and azobenzene (after completion of the nitrosobenzene plus aniline reaction). With respect to ozone consumption, their yields are very low (∼0.5%, ∼0.7% and ∼0.02%, respectively; Tekle-Röttering, private communication). This indicates that ozone attack at nitrogen is a very minor reaction.
Concerning the mechanism of their formation, one has to take into account that nitrobenzene is a primary product despite the fact that it requires two oxidation equivalents.
The NO–OO−bond length in the species formed in reaction (13) is long (1.812 Å), and this intermediate would readily release O†−2 . Once protonated [cf. reactions (14) and (15)], the intermediate becomes so unstable that upon optimisation of the structure it releases HO†2 [reaction (16)]. A bimolecular decay of the nitroxyl radical, assisted by water [reaction (17)] giving rise to aniline and nitrobenzene is energetically feasible [reaction (18),ΔG0= −83 kJ mol−1].
Nitrosobenzene may be formed in the disproportionation of the nitroxyl radical with HO†2[reaction (19), e.g. in the cage]. The reaction of nitrosobenzene with aniline to form azobenzene [reaction (20)] is a slow postozonation process. The kinetics of this reaction is well documented (Yuneset al., 1975; Dalmagroet al., 1994).
The reactions at nitrogen, although quite interesting as such, are of little importance in comparison to an addition at the ring. Here most product escaped detection, except pyridine-2-carboxylic acid which seems to be derived from the ozonide formed upon closing of theortho ozone adduct (not shown, cf. Chapter 7) [reactions (21)–(24)].
Ozone addition to the ring may be followed by a release of O3•−[e.g. reaction (25)].
NH2 NH2
H O O O
- H+
NH - O3
(25) (26)
The high•OH yield (precursor: O3•−) given in Table 8.4 must be due to this reaction. Aromatic radical cations are in equilibrium with the corresponding radicals. The pKa value of the aniline radical cation is 7.05. As expected, substituents experience a strong effect of the pKavalues expressed as a free-energy relationship (27) (Jonssonet al., 1994, 1995).
pKa=7.09−3.176
i=2
s+i (27)
Aniline radical cations are also formed upon•OH attack on aniline (Qinet al., 1985), and products observed there may also be of some relevance for aniline ozonolysis. Beyond those mentioned above, there are no further products at the level of low-molecular-weight compounds, and, most likely, the major products are hidden in the oligomer fraction (condensation products with aniline), which is not yet fully elucidated.
Deficits in the material balance between ozone and amine consumption have been reported for diclofenac, and it has been suggested that there may be a chain reaction that destroys ozone in competition with its reaction with amines (Seinet al., 2008) [reactions (28) and (29)] (see also Chapter 13).
N R R
O3
(28) N R R
O + O2 O3 (29) N
R R
+ 2 O2
Quantum chemical calculations were carried out with morpholine as a model system. They show that both reactions are exergonic (ΔG°= −77 kcal mol−1and−23 kcal mol−1, respectively, Naumov & von Sonntag, 2011, unpublished). A stable nitroxyl radical, TEMPO, reacts indeed very fast with ozone (k= 1.3×107M−1s−1) (Muñoz & von Sonntag, 2000a).
8.2.3 Nitrogen-containing heterocyclic compounds
Pyridine reacts with ozone (Table 8.1) about as fast as benzene (k=2 M−1s−1, Table 7.1), many orders of magnitude slower than most other nitrogen-containing compounds. In the presence of tBuOH as •OH scavenger, which substantially protects pyridine from getting additionally degraded, the major product (ca. 80% of pyridine degraded) is theN-oxide (Andreozzi et al., 1991) [reactions (30) and (31)]. This indicates that the major primary site of ozone attack is the nitrogen.
N
Pyridine
O3 N
O O O
N O
+ 1O2
Pyridine-N-oxide
(30) (31)
According to quantum-chemical calculations, N-adduct formation [reaction (30)] is exergonic (ΔG0= −49 kJ mol−1) and the NO–OO bond in the adduct is very long (2.085 Å, Naumov & von Sonntag 2011, unpublished). Thus, the subsequent release of 1O2 is already preformed in the adduct [reaction (31),ΔG0= −81 kJ mol−1]. The low rate constant despite the high driving force for this reaction is analogous to the reaction of ozone with dimethyl sulfoxide (Chapter 9), but is not yet fully understood and may be due to a coulombic repulsion of ozone and the pyridine nitrogen resulting in substantial activation energy of this reaction. A reaction by addition to the ring seems unlikely as the standard Gibbs free energy for addition is too positive (ΔG0.+158 kJ mol−1) to account for the observed rate constant (cf. Chapter 7).
Quinoline reacts much faster than pyridine (Table 8.1). Oxidation of intermediates with H2O2 after ozonation leads to quinolinic acid as the major product (Andreozziet al., 1992).
Quinoline
Quinolinic acid
N N
O
O OH OH
This indicates a change in mechanism. It is now the benzene ring that is mainly attacked (note the high ozone rate constant of naphthalene (Chapter 7, Table 7.1). It seems that the formation of quinoline-N-oxide has not been looked for. Thus, to what extent an attack at nitrogen also takes place is as yet not known.
With atrazine, the ozone rate constant is low (Table 8.1). Ozone attack at the ring can be excluded (cf. pyridine) and ozone attack must be at the nitrogens.
Atrazine N
N N Cl
N N
H C CH3
H3C
H C CH3 H H H
There are two types of nitrogens, and data are not yet available for deciding the preferred site.
2-Isopropyl-3-methoxypyrazine (IPMP) is a potent taste and odour compound (Chapter 5). Similarly to atrazine, ozone attack will probably occur at the nitrogens. An activation by the methoxy group leads to a higher rate constant.
2-Isopropyl-3-methoxy-pyrazine (IPMP)
N O N
CH3
H3C H3C
8.3 MICROPOLLUTANTS WITH NITROGEN-CONTAINING FUNCTIONS