JOURNAL OF MASS SPECTROMETRY J. Mass Spectrom. 2005; 40: 546–548 Published online 15 February 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jms.822 JMS Letters Received 5 November 2004; Accepted 22 December 2004 Dear Sir, Electrospray ionization mass spectrometry: a powerful tool to investigate the oligomerization mechanism of tetrahydrofuran by phosphoryl chloride The ring-opening polymerization of tetrahydrofuran (THF) initiated by trialkyloxonium salts was first described by Meerwein 1 in 1939. In subsequent studies, 2 several initiators were also found to be effective in THF polymerization to high molecular mass polymers. 3–7 Reaction of THF with a variety of inorganic acid chlorides, such as POCl 3 , SOCl 2 and SiCl 4 , together with catalysts, such as Zn, ZnCl 2 , H 2 SO 4 , TiCl 4 , BCl 3 and MoCl 5 , were also examined. 8–11 These reactions produce open-chain oligomers of THF (1; R, R 0 D OH, Cl, Br; n ½ 0) in which the degree of polymerization depended greatly on the reaction conditions. However, the detailed mechanism of the reaction of THF with POCl 3 has not been investigated. O R R′ n 1 L Correspondence to: Yu-Fen Zhao, Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005, China. E-mail: yfzhao@xmu.edu.cn Contract/grant sponsor: Chinese National Science Foundation; Contract/grant number: 20175026. Contract/grant sponsor: Fujian Key Foundation of Science and Technology; Contract/grant number: 2001F008. It is remarkable that halogen-containing compounds are very useful intermediates in organic synthesis. 7 For example, they can react with nucleophiles such as amines and alkoxides to give corresponding substituted products. In this paper, positive-ion mode electrospray ionization mass spectrometry (ESI-MS) was applied to trace the process of polymer- ization. Mass spectra were acquired using a Bruker ESQUIRE-3000- plus-LC ion trap spectrometer equipped with a gas nebulizer probe, capable of analyzing ions up to m/z 6000. Nitrogen was used as drying gas at a flow-rate of 41 min 1 . The nebulizer pressure was 7 psi. The capillary was typically held at 4 kV. The samples dissolved in methanol were ionized by ESI and continuously infused into the ESI chamber at a flow-rate of 4 μl min 1 with a Cole-Parmer Model 74 900 syringe pump. The MH C ions were analyzed by multi-stage tandem mass spectrometry through the collision with helium. We found that phosphoryl chloride is able to promote the ring opening and polymerization of THF followed by a sequence of successive nucleophilic reactions simply by non-catalytic refluxing. In order to reveal the reaction mechanism, at various time intervals, 0.5 ml of the solution was quenched with water and tested immediately by positive-ion mode ESI-MS. It was found that when the reaction proceeded for 4 h, the peaks of a series of products at m/z 261, 333, 405 and 477 with a spacing of 72 Da, other than that of phosphoric acid and related compounds, peaks at m/z 99 (protonated H 3 PO 4 ) and 197 (proton-bound dimer of H 3 PO 4 ), are formed, as shown in Fig. 1, MS(1). As the reaction time was increased to 6–7 h, in addition to the series mentioned above, two new series of compounds formed, namely one series at m/z 251, 323, 395 and 467 with a spacing of 72 Da, as shown in Fig. 1, MS(2), and the other at m/z 271, 343, 415 and 487, as shown in Fig. 1, MS(3). It should be noted that all the spacings of these three homologous series of compounds are 72 Da, which corresponds to one molecule of THF. Hence the production of all three series of compounds with different structures are due to the polymerization of THF. The relationship of these three types of compounds deduced through their relative appearance rates is shown in Scheme 1. First, the nucleophilic attack on POCl 3 by the oxygen atom on THF gives Intens x10 5 x10 5 x10 4 x10 4 2 1 1.0 0.5 0.0 0 6 4 2 0 6 4 2 0 100 200 300 400 500 m/z 99.2 99.2 99.2 102.3 127.1 163.0 196.9 127.1 127.1 163.0 171.0 171.0 196.8 196.8 196.8 260.8 260.9 250.9 260.9 271.0 342.8 414.8 486.8 477.0 549.0 405.0 294.6 332.9 332.9 322.9 395.0 405.0 332.9 404.9 476.9 467.0 477.0 549.0 +MS 2 hours +MS 4 hours 72 72 72 72 72 72 72 72 72 MS (1) +MS 6 hours MS (2) +MS 7 hours MS (3) Figure 1. Positive-ion mode ESI mass spectra for tracing the reaction of phosphoryl chloride refluxing in THF at different times. Copyright  2005 John Wiley & Sons, Ltd.