Kinetic studies of the reaction of phenacyl bromide derivatives with sulfur nucleophiles Gamal Abdel-Nasser Gohar a,b *, Sherine Nabil Khattab a *, Omaima Osman Farahat a and Hosam Hassan Khalil a The reaction of the substituted phenacyl bromides 1a–e and 2a–e with thioglycolic acid 3 and thiophenol 6 in meth- anol underwent nucleophilic substitution S N 2 mechanism to give the corresponding 2-sulfanylacetic acid derivatives 4a–e, 5a–e and benzenethiol derivatives 9a–e, 10a–e. The reactants and products were identified by mass spectra, infrared and nuclear magnetic resonance. We measured the kinetics of these reactions conductometrically in meth- anol at a range of temperatures. The rates of the reactions were found to fit the Hammett equation and correlated with s-Hammett values. The r values for thioglycolic acid were 1.22–1.21 in the case of 4-substituted phenacyl bro- mide 1a–e, while in the case of the nitro derivatives 2a–e they were 0.39–0.35. The r values for thiophenol were 0.97–0.83 in the case of 4-substituted phenacyl bromide 1a–e, while in the case of the nitro derivatives 2a–e they were 0.79–0.74. The Brønsted-type plot was linear with a a = 0.41 0.03. The kinetic data and structure-reactivity relationships indicate that the reaction of 1a–e and 2a–e with thiol nucleophiles proceeds by a concerted mecha- nism. The plot of log k 45 versus log k 30 , the plot log(k x,3-NO2 /k H ) versus log(k x /k H ), and the Brønsted-type correlation indicate that the reactions of the thiol nucleophiles with the substituted phenacyl bromides 1a–e and 2a–e are at- tributed to the electronic nature of the substituents. Copyright © 2011 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper. Keywords: conductometric studies; kinetic measurements; linear free energy relationship; nucleophilic substitution; phena- cyl bromide derivatives; reaction mechanism; substituent effects; transition state INTRODUCTION a-Haloketones, first obtained and described as early as the end of the 18th century, have been attracting increasing attention in view of their high reactivity. They are the building blocks for the preparation of compounds of various classes because of their selective transformation with different reagents. [1] Especially, phenacyl halide derivatives are among the most versatile inter- mediate in organic synthesis and their high reactivity make them prone to react with a large number of nucleophiles [2–26] to pro- vide a variety of useful compounds. They are widely used for the preparation of biologically active heterocyclic com- pounds, [27–33] synthesis of photo-functional polymers, [34] precol- umn fluorescence derivatization of cytosine-containing compounds in HPLC, [35] optimal separation of free fatty acids from human plasma, [36] inhibition of some enzymes, [37–39] syn- thesis of organic semiconductors with optical and electrical con- duction properties, [40,41] usage as photoreleasable protecting groups, [42] and preparation of antibiotics. [43] RESULTS AND DISCUSSION The 2-sulfanylacetic acid derivatives 4a–e and 5a–e were pre- pared by the addition of sodium hydroxide solution (2 equiva- lents) to one equivalent of 2-sulfanylacetic acid in methanol to yield the corresponding disodium salt of the 2-sulfanylacetic acid 3. The sodium salt of the 2-sulfanylacetic acid was then added to the substituted phenacyl bromides 1a–e and 2a–e with stirring. The reaction mixture was neutralized by hydrochloric acid (Scheme 1). The structure of products 4a–e and 5a–e was confirmed by infrared (IR), 1 H-NMR and mass spectra (see Experimental part). The benzenethiol derivatives 9a–e, 10a–e, 11 and 12 were prepared by the addition of sodium hydroxide solution (one equivalent) to one equivalent of benzenethiol 6, 4-methylbenze- nethiol 7 or 4-chlorobenzenethiol 8 to yield the corresponding sodium salts. The benzenethiolate was added to the substituted phenacyl bromides 1a–e and 2a–e with stirring giving 9a–e and 10a–e, respectively. Similarly, 4-methylbenzenethiolate and 4- chlorobenzenethiolate were allowed to react separately with 2- bromo-1(3-nitrophenyl) ethanone 2a solution in methanol to give 11 and 12 (Scheme 2). The structure of products 1-(4-substi- tuted phenyl)-2-(phenylthio)ethanones 9a–e, 1-(4-substituted-3- nitrophenyl)-2-(phenylthio)ethanones 10a–e, 1-(3-nitrophenyl)- 2-(p-tolylthio)ethanones 11 and 2-(4-chlorophenylthio)-1-(3- nitrophenyl) ethanone 12 was confirmed spectroscopically (see Experimental part). * Correspondence to: Gamal Abdel-Nasser Gohar, Sherine Nabil Khattab, Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia 21321, PO Box 426, Alexandria, Egypt. E-mail: gohar_g@link.net; ShKh2@link.net a G. A.-N. Gohar, S. N. Khattab, O. O. Farahat, H. H. Khalil Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia 21321, Alexandria, Egypt b G. A.-N. Gohar Faculty of Medical and Applied Sciences, Jazan University, Jazan, Saudi Arabia J. Phys. Org. Chem. 2012, 25 343–350 Copyright © 2011 John Wiley & Sons, Ltd. Research Article Received: 03 October 2010, Revised: 17 February 2011, Accepted: 04 July 2011, Published online in Wiley Online Library: 25 August 2011 (wileyonlinelibrary.com) DOI: 10.1002/poc.1921 343