Reactions of N, O- and N, S-Azoles and -Azolines with Ozone: Kinetics and Mechanisms

Abstract

N,O- and N,S-azoles and -azolines are common functional groups in pharmaceuticals, agrochemicals and natural products. Their fate during ozone-based water treatment processes is unknown due to a lack of kinetic and mechanistic information on their reactions with ozone. Apparent second-order rate constants k_O3 of 12 model compounds were determined at pH 7: oxazoles react 2 orders of magnitude faster (k_O3 = 9 × 10²-5 × 10⁴ M^-1s^-1, depending on their substituents) than thiazoles (k_O3 = 1 × 10¹-2 × 10³ M^-1s^-1). The low k_O3 of thiazoles limits their degradability during ozonation. Only small yields of reactive oxygen species (^•OH, H₂O₂, and ¹O₂) were observed during ozonation of oxazoles, suggesting that all oxygen atoms from ozone are incorporated into the products. Oxazoles and thiazoles react initially by a Criegee-type reaction at the C=C double bond, followed by two reaction branches, leading to two observed product groups: (1) carboxylates and cyanate; (2) formate, amide and CO₂. For thiazoles, thiocarboxylic acids were identified as intermediates, reacting further to sulfate and carboxylic acids, forming ¹O₂. The nonaromatic 2-methyloxazoline is unreactive toward ozone. 2-Methylthiazoline reacts fast (k_O3 = 2 × 10⁴ M^-1s^-1), forming ¹O₂, leading to ring-opening and formation of dimerization products which react further to N-acetyltaurine. These results enhance the understanding of the ozone reactivity of heterocycles and help predict transformation product formation.

Keywords: aromatic and nonaromatic N-heterocycles; oxazole; oxazoline; ozonation; thiazole; thiazoline.

1

Abatement of (a) oxazole and (b) thiazole and formation of detected transformation products as a function of the molar [ozone]:[azole] ratio. Results are shown as averages from duplicate experiments, error bars represent the upper and lower value (if not visible, the range falls within the symbol size). The C, N and S mass balances for the transformation of (a) oxazole and (b) thiazole are shown at the bottom, which are obtained by the sum of the compound concentrations multiplied by the number of respective atoms in the compound at every ozone dose relative to the initial concentration of azole. The experiments were performed in the presence of the ^•OH scavenger tert-butanol. Experimental conditions: [azole] = ∼0.1 mM; ozone doses = 0–0.5 mM; [tert-butanol] = 10 mM; [phosphate buffer (pH 7)] = 5 mM.

2

Abatement of (a) 2-methyloxazole and (b) 2-methylthiazole and formation of detected transformation products as a function of the molar [ozone]:[azole] ratio. Results are shown as average from duplicate experiments, error bars represent the upper and lower value (if not visible, the range falls within the symbol size). The C, N and S mass balances are shown at the bottom, which are obtained by the sum of the compound concentrations multiplied by the number of respective atoms in the compound at every ozone dose relative to the initial concentration of azole. The experiments were performed in the presence of the ^•OH scavenger tert-butanol. Experimental conditions: [azole] = ∼0.1 mM; ozone doses = 0–0.5 mM; [tert-butanol] = 10 mM; [phosphate buffer (pH 7)] = 5 mM.

1. Proposed Reaction Mechanisms for the Reaction of 1,3-Azoles with Ozone based on the Identified and Quantified Reaction Products (Highlighted in Blue, according to Figures and )­

2. Reaction of 2-Methylthiazoline (S1) with Ozone; (a) Proposed Reaction Scheme to Disulfide I1, Which is Further Oxidized to the Organic Thiosulfinate Ester I2 in a Second Step and Finally to N-Acetyltaurine (P1); (b) Proposed Detailed Reaction Mechanism for the Formation of I1 (Bottom Pathways, Reaction (1)) and Possible Mechanism of the Formation of P1, without Dimerization (Blue, Upper Pathway)

3

Abatement of 2-methylthiazoline during ozonation and formation of S-containing transformation products quantified by LC-ICP-MS/MS. (a) 2-Methylthiazoline abatement and formation of the intermediates I1, I2 and I3 and the final product P1 (for chemical structures, see Scheme ) as a function of the molar [ozone]:[S1] ratio in the presence of the ^•OH scavenger tert-butanol. Experimental conditions: [2-methylthiazoline] = ∼0.1 mM; ozone doses = 0–0.4 mM; [tert-butanol] = 10 mM; [phosphate buffer (pH 7)] = 5 mM. Results are shown from a single experiment. Error bars represent the upper and the lower measured value of two injections (if not visible, the range falls within the symbol size). Ozone doses were not determined with a separate reaction vessel (see Section ). The results of a replicate experiment with slightly different ozone doses are shown in Figure S10.3. (b) Product formation from the ozonation of 2-methylthiazoline as a function of the molar excess of 2-methylthiazoline for a constant ozone dose (0.1 mM). Results are shown as averages from triplicate experiments, error bars represent the corresponding standard deviations.