Anal Bioanal Chem (2006) 385: 910–917 DOI 10.1007/s00216-006-0477-3 ORIGINAL PAPER Michael Maiwald . Thomas Grützner . Eckhard Ströfer . Hans Hasse Quantitative NMR spectroscopy of complex technical mixtures using a virtual reference: chemical equilibria and reaction kinetics of formaldehyde–water–1,3,5-trioxane Received: 4 December 2005 / Revised: 2 April 2006 / Accepted: 5 April 2006 / Published online: 12 May 2006 # Springer-Verlag 2006 Abstract Quantitative 1 H NMR spectroscopy was used to study chemical equilibria and reaction kinetics of both the formation and decomposition of 1,3,5-trioxane in aqueous formaldehyde solutions. The reaction was homogeneously catalyzed with up to 0.10 g g -1 sulfuric acid at temperatures between 360 and 383 K so that most of the experiments had to be carried out pres- surized. The studied mixtures were complex due to the formation of methylene glycol and poly(oxymethylene) glycols in aqueous formaldehyde and the presence of considerable amounts of ionized species. Most common internal standards are decomposed by the hot sulfuric acid and external standards were not applicable using the flow NMR probe or pressurizable NMR sample tubes. Therefore, for the quantification of the small trioxane signals, a novel procedure was applied, in which elec- tronically generated NMR signals were used as highly stable Virtual References (VR). The NMR decoupler channel with wave-form generator was used as the source of the reference signal, which was irradiated into the probe using the lock coil. Details on the experimental procedure are presented. It is shown that the presented method yields reliable quantitative reaction data for the complex studied mixtures. Keywords NMR spectroscopy . Quantitative spectroscopy . Virtual reference . 1,3,5-trioxane . Formaldehyde Introduction Formaldehyde (CH 2 O) is one of the most important inter- mediate products of the chemical industry [1]. Due to its high reactivity, pure formaldehyde is technically un- available. Therefore, formaldehyde is mainly processed in aqueous solutions, which usually also contain some methanol in small amounts. These solutions are complex mixtures in which formaldehyde is predominately bound in methylene glycol and poly(oxymethylene) glycols and corresponding hemiformals. If water-free formaldehyde is needed, as for the production of polymers, usually 1,3,5- trioxane is used [1, 2], the cyclic trimer of formaldehyde. Trioxane is usually produced from aqueous formaldehyde solutions by homogeneous catalysis with sulfuric acid at temperatures up to 373 K. It is almost entirely used for producing high-performance plastics such as polyoxy- methylenes (POM) [3]. For the design and optimization of the production process, knowledge of the chemical equilibria and reaction kinetics of this system is needed. Extensive NMR spectroscopic studies on chemical equi- libria and reaction kinetics of the oligomerization reactions in formaldehyde-containing solutions are available; recent work stems from Balashov et al. [4, 5], Albert et al. [6, 7], Hahnenstein et al. [8, 9], Ott et al. [10, 11], and Maiwald et al. [12, 13]. These studies cover the binary systems formaldehyde-water, formaldehyde-methanol and the ter- nary system formaldehyde-water-methanol. Very little is known about the formation of trioxane in aqueous formaldehyde solutions, for which only Walker [2], Moedritzer et al. [14], Elenkov et al. [15, 16], and Bartholomé et al. [17] present results without reporting M. Maiwald . T. Grützner . H. Hasse (*) Institut für Technische Thermodynamik und Thermische Verfahrenstechnik, Universität Stuttgart, 70550 Stuttgart, Germany e-mail: hasse@itt.uni-stuttgart.de Tel.: +49-711-6856105 Fax: +49-711-6856140 E. Ströfer BASF AG, 67056 Ludwigshafen, Germany T. Grützner Lonza AG, R&D Organic Fine Chemicals-OCNC, 3930 Visp, Switzerland Present address: M. Maiwald Merck KGaA, Central Services Analytics, 64293 Darmstadt, Germany