Journal of Hazardous Materials A113 (2004) 1–10 (S)-Nitroxycarnitine nitrate production from (S)-carnitine by using acetic anhydride/nitric acid/acetic acid mixtures: safety assessment R. Andreozzi a,∗ , V. Caprio a , R. Castagnani b , R. Marotta a , R. Sanchirico c a Universit` a di Napoli “Federico II”, p.le V. Tecchio, 80-80125 Napoli, Italy b Biosint, via del Murillo, 16-04010 Sermoneta (LT), Italy c Istituto di Ricerche sulla Combustione (CNR), p.le V. Tecchio, 80-80125 Napoli, Italy Received 4 November 2003; received in revised form 29 April 2004; accepted 29 April 2004 Available online 3 August 2004 Abstract The present work aims at assessing both thermodynamic and kinetic parameters of the esterification process of the (S)-carnitine, using calorimetric techniques. The use of the system acetic anhydride/nitric acid/acetic acid as esterifying agent and the explosive behaviour of nitric esters lead to safety considerations that have been investigated by hypothesizing some common process deviations. In particular, it has been investigated in adiabatic conditions both the batch addition of acetic anhydride and the effect of an initial temperature higher than those required by the process. © 2004 Elsevier B.V. All rights reserved. Keywords: Carnitine; Esterification; Adiabatic; Kinetic; Safety 1. Introduction During last years, a growing interest has been recorded in developing industrial processes [1] for the (R)-carnitine production starting from the corresponding S enantiomer, a low cost raw material which is currently obtained as a side-product in the resolution of racemic mixtures of (R,S)- carnitine. Quoted processes are not free of drawbacks consist- ing mainly in the formation of large amounts of by-products and in the multiple steps production sequences. A new process has been recently patented [2], in which the inversion of the S form is realized through the preparation of the corresponding carnitine nitric ester, with the same ab- solute configuration of the starting molecule (S), which gives rise, in alkaline medium, to the formation of (R)-carnitine with high yield ( 80%). ∗ Corresponding author. Tel.: +39 081 7682251; fax: +39 081 5936936. E-mail address: roberto.andreozzi@unina.it (R. Andreozzi). The success of this process seems to rely on the adoption of acetic anhydride/nitric acid/acetic acid as “esterifying” system instead of the classic mixed acid solutions. In fact, the milder conditions ensured by the former system seem to favour the obtainment of a nitroxycarnitine derivative at high yield, with a reduced occurrence of secondary reactions. Although not completely elucidated, the mechanism of re- action through which the system Ac 2 O/HNO 3 works is gen- erally reported to involve the formation of acetyl nitrate as intermediate [3]. This species is known to undergo violent decomposition on heating [4], with spontaneous explosion of its solutions being reported also at ambient temperature during the storage [5]. The results of a recent investigation on the thermal be- haviour of Ac 2 O/HNO 3 mixtures indicate that this system can give rise to violent exothermic decomposition with the devel- opment of huge amount of gases with the released energy and heat rates strictly depending on the ratio (mol Ac 2 O)/(mol HNO 3 ) [6]. The present work aims therefore at studying the safety aspects of the process for the preparation of nitrox- 0304-3894/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jhazmat.2004.04.020