The Acidities of Some 1- substituted -1 H - Benzotriazole Derivarives

1. TheAcidities of Some 1-substituted-1H-BenzotriazoleDerivarives İlker AVAN*, AlaattinGÜVEN Department of Chemistry, Faculty of Science, Anadolu University, Eskisehir 26470, Turkey Email: iavan@anadolu.edu.tr Benzotriazole methodology has been used extensively as a novel synthetic auxiliary in many useful synthetic transformations. 1-H-benzotriazole can be employed as a good substitution agent, because of its ability to be both an electron-withdrawing group and an electron-donating group, thus it is a good leaving group, because benzotriazole is a weak base (pKa=1.6[3]) as well as a weak acid (pKa=8.2). Benzotriazole can be easily eliminated from the reaction mixture by washing with base. Besides the use of benzotriazoles as a good auxiliary, the benzoriazole is readily available and quite cheap. [1-3] Some classes of 1-H-benzotriazole are used as corrosion inhibitors in various industrial processes and in households frequently in aqueous media. [4-6]  In this study, we present synthesis and experimental-theoretical study for the estimation of pKa values of some 1-substituted-1H-benzotriazole derivatives in aqueous solution by spectroscopic and semi empirical methods. The following 1H-benzotriazole derivatives were prepared according to the methods in the literature [7-14]. The experimental pKa values of benzotriazole derivatives were measured by UV spectroscopic method. The theoretical pKa values of benzotriazole derivatives have been calculated in aqueous solution (ε=78.4) by the means of semi empirical and AM1 cosmo method. Table 1 Experimental and theoretical studies for the estimation of pKa values of the benzotriazoles In the experimental work, pKa values of investigated compounds were found out by UV spectroscopic method [15]. AM1 and PM5 quantum chemical methods were used to calculate pKa values for benzotriazole derivatives in aqueous solution. The experimental and theoretical pKa values are given in Table 2. Scheme 7 A samplepKa calculation of 14 with UV spectroscopic method is showed below. pKa values of other molecules were similarly estimated. (Graph 1) In this case, 1-hydroxymethylbenzotriazole (2) (obtained from the well-known reaction between benzotriazole and formaldehyde [7,8]) and reaction of 1-hydroxymethylbenzotriazole (2) and SOCl2 led to the 1-chloromethylbenzotriazole (3). Reaction of 3 with sodium phenoxide , which is prepared from NaOH and phenol in EtOH-water, gave 1-(benzotriazol-1-yl)-1-phenoxyalkane (4) [9,10] (Scheme 1) Graph 1 Table 2 Scheme 1 Reaction of 2-aminoethanethiole hydrochloride with benzaldehyde gave the 2-Phenyl-thiazolidine in 89% yield and reduction of it with NaBH4 gave 2-Benzylamino-ethanethiol. [2-(Benzotriazol-1-ylmethylsulfanyl)-ethyl]-benzyl-amine (6) was obtained from the reaction between 2-Benzylamino-ethanethiol and 1-chloromethylbenzotriazole (3) (Scheme2) Scheme 2 Reaction of 2-aminoethanethiole hydrochloride with 1-chloromethylbenzothriazole gave the S-benzotriazolylmethyl derivative in 91% yield. Reaction of it with p-toluylchloride gave N-[2-(Benzotriazol-1-ylmethylsulfanyl)-ethyl]-4-methyl-benzamide (7) in 85% yield. (Scheme 3) Scheme 3 Etil α-benzotriazolyl ester derivatives (8-11) are synthesized from the reaction between etil α-bromo derivatives and benzotriazole (1 (Bt)) in toluene with several hours in good yields. [11-13] (Scheme 4) Scheme 4 Reaction of benzotriazole and N-substituted-2-chloroacetamides (12-16) led to the N-substituted-2-(benzotriazolyl-1-yl)acetamides in good yields. N-substituted-2-chloroacetamides were obtained from the reactions between amines and 2-substituted-2-chloroacetylchlorides. [14] (Scheme 5) In quantum chemical studies, the acidities of investigated compounds in aqueous solution can be calculated as following: a δΔG0(BH+)= [ΔG0(B) + ΔG(H3O+)] - [ΔG0(BH+)+ ΔG0(H2O)] ; ΔG0(H3O+)=30.11 kcal/mol, ΔG0(H2O)=-81.91 kcal/mol b pKa(BH+)= δΔG0(BH+)/[2.303RT] (R=1.987 cal/mol.K, T=298oK) Scheme 5 Reaction of methyl acrylate with the dianionic intermediate obtained from N-n-butyl-2-(benzotriazol-1-yl)acetamide (12) gave the product (17) instead of the expected glutarimide (Scheme 6). Reaction of methyl acrylate with the dianionic intermediate obtained from N-n-butyl-2-(benzotriazol-1-yl)-2-methylacetamide (13) gave only starting material (13). (Scheme 6) References: [1] Katritzky A. R.,. Lan X. F., Yang J. Z., Denisko O. V., Chem. Rev., 1998, 98, 409. [2] Zheng Y., Lu G., Zhang Y., J. Chem. Research (S). 1999, 682-3 [3] Lide D.R., “Handbook of Chemistry and Physichs”, 84th Edition, CRC Press, 2003-2004 [4] Weiss S., Reemtsma T., Anal. Chem. 2005, 77, 7415-20 [5] Per W., Ind. Eng. Chem. Res. 2007, 46, 3312-16 [6] Mamaş S., Kıyak T., Kabasakaloğlu M., Koç A., Mat. Chem. and Phys., 2005, 98, 41-47 [7] Liu, Qing-Xiang; Xu, Feng-Bo; Li, Qing-Shan; Zeng, Xian-Shun; Leng, Xue-Bing; Zhang, Zheng-Zhi. Chinese Journal of Chemistry, 2002, 20(9), 878-883. [8] Gaylord, N.G.; Kay, D. J., Journal of Organic Chemistry, 1958, 23, 1574-5. [9] Katritzky, Alan R.; Rachwal S., Rachwal B., Journal of Organic Chemistry, 1989, 54(26) 6022-9. [10] Katritzky, Alan R.; Serdyuk, Larisa; Xie, Linghong., Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry, 1998, 6, 1059-1064. [11] Katritzky, Alan R.; Wu, Jing., Synthesis, 1994, 6, 597-600. [12] Zhang, Xin-Ming; Xie, Xiao-juan; Tao, Gui-de; Tong, Xiao-tian, Anhui Shifan Daxue Xuebao, Ziran Kexueban, 2001, 24(2),136-7, CAN: 136:279397. [13] Sparatore, F.; La Rotonda, M. I.; Caliendo, G.; Novellino, E.; Silipo, C.; Vittoria, A., Farmaco, Edizione Scientifica 1988, 43(1), 29-47. [14] Su, Weike; Yang, Bibo; Li, Yongshu, Journal of Chemical Research, Synopses, 2002, 11, 542-543. [15] Albert A., Serjeant E.P., “The Determination of Ionization Constants”Chapman & Hall, New York, 1984 [16] Katritzky, Alan R.; Ghiviriga, I; Oniciu, D. C.; Soti, F., Journal. of Heterocyclic Chemistry, 1996, 33(6), 1927-34. Scheme 6