Synthesis Of Benzalkonium Salt

Molecules 2007, 12, 2341-2347

molecules
ISSN 1420-3049 © 2007 by MDPI www.mdpi.org/molecules Communication

Preparation of Benzalkonium Salts Differing in the Length of a Side Alkyl Chain
Kamil Kuca 1,2,3, Jan Marek 4,5, Petr Stodulka 1, Kamil Musilek 2,5,*, Petra Hanusova 4, Martina Hrabinova 1 and Daniel Jun 1,2
1 2 3

4 5

Center of Advanced Studies, Faculty of Military HealthSciences, Hradec Kralove, Czech Republic Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic Department of Chemistry, Faculty of Sciences, J.E. Purkinje University, Usti nad Labem, Czech Republic Vakos XT, Prague, Czech Republic Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic

* Author to whomcorrespondence should be addressed; E-mail: musilek@pmfhk.cz Received: 3 September 2007; in revised form 3 October 2007 / Accepted: 4 October 2007 / Published: 24 October 2007

Abstract: Benzalkonium salts are widely used as disinfectants, biocides and detergents, among a variety of other applications. The cationic surface-activity of these salts determines their potential to act as a biocide on both targetand non-target organisms. In this study, a quick synthesis of a complete set of the benzalkonium salts differing in the length of an alkylating chain (from C2 to C20) is described. Moreover, their 1H-NMR, HPLC-MS, TLC and HPLC analysis were recorded. Keywords: Benzalkonium salt, detergent, surfactant, biocide, HPLC, TLC.

Introduction Quaternary compounds, including the benzalkonium salts,constitute an economically important class of industrial chemicals that are widely distributed among a diverse array of products and users

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from an industrial to the household sector. Because of their strong cationic surface activity, quaternary compounds are used primarily as disinfectants, biocides, and detergents, but also as anti-electrostatics, and as phasetransfer catalysts [1]. Very important features of benzalkonium salts are their bactericidal and antimicrobial properties. The antimicrobial activity depends on a changing length of the side n-alkyl chain. It is well known that the C12-homolog is most effective against yeast and fungi, the C14-homologue against gram-positive bacteria and C16-homolog against gram-negative bacteria [2]. For these reasonsthey are widely used as preservatives for ophthalmic, nasal and parenteral products. They are also used as topical antiseptics and disinfectants for medical equipment [3-6]. These compounds are not generally used as single components, but rather as mixtures composed of two or three benzalkonium members differing only in the length of the alkyl chains [7-8]. Such mixtures are produced on alarge-scale in industry. However, a targeted synthesis of pure individuals could be of interest because of the above-mentioned specificity of each salt against different pathogens. Preparation of these compounds has been described previously [9-12], but a general synthesis applicable to the whole series of benzalkonium salts is lacking. The synthesis of long chain derivatives (C8-C20) was described earlierby our group [13]. To provide a synthetic route to such compounds, the preparation of the whole set of these compounds (C2-C20) is now shown. A new set of the short chain benzalkonium salts was developed and the preparation of the long chain benzalkonium salts was improved. Results and Discussion The N-benzyl-N,N-dimethylalkyl bromides 3-12 were prepared by the general method shown in Scheme 1.Scheme 1. Preparation of benzalkonium salts.
N EtOH R-Br 2 reflux 3 - 11 N

R

Br

1

Yields of all reactions, together with the melting points of the prepared salts, are shown in Table 1. Thin-Layer Chromatography (TLC) retention factors and High Pressure Liquid Chromatography (HPLC) retention times for of all the salts are also listed in this table. The yields achieved in this study...