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

  

İlker AVAN*, Alaİlker AVAN*, Alaaattin GÜVENttin GÜVEN

Department of Chemistry, Faculty of Science, Anadolu University, Eskisehir 26470, TurkeyEmail: 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 ( =78.4) by the means of semi empirical ε and AM1 cosmo method.

Compounds Neutral

(max)λ nm

/(log )ε

Monocationic

(max)λ nm

/(log )ε

Applied

λnm

Expt.

pKa

(BH+)

(This

work)

AM1

pKa

(BH+)b

(This work)

Neutral

HΔ f

(kcal/mol)

BtR

Cationic

HΔ f

(kcal/mol)

BtR-3H+

Neutral

SΔ(cal/mol.K)

BtR

Cationic

SΔ(cal/mol.K)

BtR-3H+

Neutral

GδΔ fa

(kcal/mol)

BtR

Cationic

GδΔ fa

(kcal/mol)

BtR-3H+

2 260.9 (3.74) 271.7 (3.82) 272.0 -0.60 -0.61 51.97 167.62 92.00 92.60 24.55 140.03

3 257.0 (3.87) 276.8 (3.89) 278.0 -1.53 -1.61 95.56 212.46 118.11 118.30 60.36 177.21

4 257.0 (3.86) 276.6 (3.95) 276.8 -1.29 -3.04 93.01 211.78 93.87 93.77 65.04 183.84

6 260.0 (3.80) 277.5 (3.84) 278.0 -1.27 -1.10 124.78 241.78 152.76 155.59 79.26 195.41

7 244.3 (3.89) 259.4 (3.95) 258.0 -2.49 -2.35 79.40 197.33 165.23 165.48 30.16 148.02

8 257.2 (3.83) 276.0 (3.96) 274.5 -1.01 -1.47 10.49 128.49 118.83 123.31 -24.92 91.74

9 261.9 (3.76) 276.0 (3.88) 275.0 -1.03 -0.73 7.66 127.39 120.10 127.39 -28.13 87.51

10 262.0 (3.67) 276.2 (3.81) 275.0 -1.03 -2.53 1.49 119.66 135.71 135.91 -38.95 79.16

11 262.6 (3.83) 275.7 (3.96) 275.0 -0.49 -2.09 -11.17 106.56 149.83 150.61 -55.82 61.68

12 258.0 (3.84) 276.5 (3.87) 276.0 -1.37 -2.23 55.62 172.94 122.75 121.52 19.04 136.73

13 258.0 (3.74) 276.3 (3.79) 276.0 -1.19-2.10 41.95 159.25 137.53 136.78 0.97 118.49

14 258.5 (3.88) 276.3 (3.92) 276.0 -1.14 -2.33 38.05 155.81 141.82 141.58 -4.21 113.62

15 249.3 (4.16) 274.7 (4.01)

241.0 (4.01)

275.0 -1.55 -2.42 95.57 213.13 128.57 127.22 57.26 175.22

16 258.0 (3.91) 276.5 (3.96) 276.0 -1.30 -1.87 88.35 205.90 132.55 133.74 48.85 166.05

17 256.5 (4.15) 261.2 (4.04) 256.5 -1.42 -1.82 -80.40 38.11 188.55 190.16 -135.7 -18.56

Compounds

1 6 12

2 7 13

3 8 14

4 9 15

5 10 16

11

17

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)

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)

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)

Etil -benzotriazolyl ester derivatives (α 8-11) are synthesized from the reaction between etil -bromo αderivatives and benzotriazole (1 (Bt)) in toluene with several hours in good yields. [11-13] (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)

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)

Experimental and theoretical studies for the estimation of pKa values of the benzotriazolesIn 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.

In quantum chemical studies, the acidities of investigated compounds in aqueous solution can be calculated as following:

a GδΔ 0(BH+)= [ GΔ 0

(B) + GΔ (H3O+)] - [ GΔ 0(BH+)+ GΔ 0

(H2O)] ; GΔ 0(H3O+)=30.11 kcal/mol, GΔ 0

(H2O)=-81.91 kcal/mol

b pKa(BH+)= GδΔ 0(BH+)/[2.303RT] (R=1.987 cal/mol.K, T=298oK)

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.

O

H EtOHrt, 24h, 89%

NH2.HClHS+ NH

S

NaBH42-propanol24h, reflux, 49%

Ph NH

SH

Bt S

HN

BtCH2-ClEtOH

6 74%

BtN

n-Bu

O

HR Na

Nn-Bu

O

BtR

Na

N OO

Bt

n-Bu

R

N OO

Bt

n-Bu

R

BtN

n-Bu

O

H

stirringrt, 24 h

+ +

19%

13%

R = HR = Me

R = Me

R = H

stirringRT, 24 h

OO

MeON O

NH

NN

n-Bu

OMe

O

OMe

O

0%

THF, NaHrt, 10min

17

1213

glutarimide12

glutarimide

A sample pKa calculation of 14 with UV spectroscopic method is showed below. pKa values of other molecules were similarly estimated. (Graph 1)

Bt OH

NN

N

HBt

MeO

O

O

O

N H

n-Bu

Bt

Bt OH

Bt Cl

Bt Cl

Bt S

NH.HCl

NH2

BtOEt

O

BtOEt

O

Me

BtOEt

O

Et

BtOEt

O

n-Bu

Bt

HN

O

Et

Bt

HN

O

n-Bu

Bt

HN

O

n-Bu

Me

Bt

HN

O

Bt

HN

O

Me

Bt S

HN

Bt S

HN

O

Me

BtOEt

O

BtOEt

O

Me

BtOEt

O

Et

BtOEt

O

n-Bu

Bt

HN

O

Et

Bt

HN

O

n-Bu

Bt

HN

O

n-Bu

Me

Bt

HN

O

Bt

HN

O

Me

Bt OPh

Bt OPh

NH2.HClHSBtCH2-ClEtOH, 91%

SBt

NH2.HCl

Cl

O

Me Bt S

HN

O

Me

7 85%

CH2Cl2

MeO

O

O

O

NH

n-Bu

Bt

Bt S

HN Ph

O

p-Me

Bt S

HN Ph

NN

N

R

NN

N

R

H

NN

N

R

H+ H3O++ H2O

BtR BtR-3H+ BtR-2H+

NN

N

HN

NN

OH

NN

N

Cl

NN

N

OPh

CH2O, H2OCH3COOH85%

SOCl270%

NaOPhEtOH55%

1, (Bt) 2 3 4ThioureaEtOH, HCl45 %

Bt S NH2

NH.HCl

5

NN

N

H1, (Bt)

BrO

O

R

Toluenreflux

BtO

O

R

R 8 H 65% . 9 Me 64% 10 Et 60% 11 n-Bu 55%

+

ClCl

OR1-NH2

-5OC, 1hCl

N

O

R1

H

Bt BtN

O

R1

H

R R1

12 H Et 59%

13 H n-Bu 61%

14 Me n-Bu 53%

15 H Ph 98%

16 H 2-C6H4CH3 89%

R R R

HΔ f

(kcal/mol)

SΔ(cal/mol.K)

GδΔ fa

(kcal/mol)

H2O -64.34 45.10 -77.81

H3O+ 50.59 46.14 36.84

Table 1

Table 2Scheme 1

Scheme 2

Scheme 3

Scheme 4

Scheme 5

Scheme 6

Scheme 7

Graph 1