LITERATURE CITED
`l. K. Monah, K. Bharamaramba, and R. V. Venkataraman, Chern. Ind., 125 (1978).
`2. G. Henbach, L. Emmel, and A. Waltersdorfer, Ger. Offen 2725148; Chern. Abstr., ~.
`196956 (1979).
`3. S. Iwai, M. Hatano, I. Ischikawa, and T. Kawano, Japan Kokai Tokkyo Koho 78135981;
`Chern. Abstr., 90, 152195 (1979).
`4. W. Manchot and~. Noll, 343, 1 (1905).
`5. G. I. Chipens, R. P. Bokaldere, and V. Ya. Grinshtein, Khim. Geterotsikl. Soedin., No.
`1, llO (1966).
`6. C. F. Kroger, K. Mietchen, H. Frank, M. Siemer, and S. Pilz, Chern. Ber., 102, 755
`(1969).
`7. G. I. Chipens and R. P. Bokaldere, Khim. Geterotsikl. Soedin., No. 2, 159 (1969).
`8. T. P. Kofman, I. V. Vasil'eva, and M. S. Pevzner, Khim. Geterotsikl. Soedin., No. 10,
`1407 {1977).
`9. T. P. Kofman, M. S. Pevzner, L. N. Zhukova, T. A. Kravchenko, and G. M. Frolova, Zh.
`Org. Khim., .!.§_, 420 (1980).
`10. L. I. Bagal, M. S. Pevzner, and V. Ya. Samarenko, Khim. Geterotsikl. Soedin., No. 2,
`269 (1970).
`11. M. S. Pevzner, T. P. Kofman, E. N. Kibasova, L. F. Sushchenko, and T. L. Uspenskaya,
`Khim. Geterotsikl. Soedin., No. 2, 257 (1980).
`12. T. P. Kofman, T. L. Uspenskaya, N. Yu. Medvedeva, and M. S. Pevzner, Khim. Geterotsikl.
`Soedin., No. 7, 991 (1976).
`13. T. P. Kofman, N. Yu. Medvedeva, T. L. Uspenskaya, and M. s. Pevzner, Khim. Geterotsikl.
`Soedin., No. 9, 1271 (1977).
`14. A. M. Ostapkovich, T. P. Kofman, L. V. Lisitsyna, and M. S. Pevzner, Izv. Vyssh.
`Uchebn. Zaved., Khim. Khim. Tekhnol., 1l, 402 (1979).
`15. T. P. Kofman, G. A. Zykova, V. I. Manuilova, T. N. Timofeeva, and M. S. Pevzner. Khim.
`Geterotsikl. Soedin., No. 7, 997 (1974).
`16. A. A. Stotskii and N. N. Tkacheva, Zh. Org. Khim., 10, 2232 (1974).
`
`TETRAZOLES.
`9.* ACID-BASE PROPERTIES OF 5-SUBSTITUTED TETRAZOLES
`
`V. A. Ostrovskii, G. I. Koldobskii,
`N. P. Shirokova, and V. S. Poplavskii
`
`UDC 547.796.1:541.121
`
`The basicities of series of 5-R-tetrazoles in aqueous solutions of sulfuric acid
`were studied by UV and PMR spectroscopy. The pKBH+ values of these compound
`correlate with the Op substituent constants. The transmission factor of the
`p-phenylene ring (TI' = 0.23) was calculated from the ratio of the reaction con(cid:173)
`stants for protonation of substituted 5-phenyltetrazoles and 5-R-tetrazoles. A
`linear dependence between the pKa values and the pKBH+ values of 5-substituted
`tetrazoles was established.
`
`It is known that tetrazoles and 5-substituted tetrazoles are heterocyclic N-H acids
`with moderate strength. When these compounds are dissolved in mineral acids, they behave
`like weak organic bases [2].
`
`*See [11 for Communication 8.
`
`Lensovet Leningrad Technological Institute, Leningrad 198013.
`Geterotsiklicheskikh Soedinenii, No. 4, pp. 559-562, April, 1981.
`mitted May 21, 1980.
`
`Translated from Khimiya
`Original article sub-
`
`412
`
`0009-3122/81/1704-0412$07.50 © 1981 Plenum Publishing Corporation
`
`

`
`Although tetrazole and 5-substituted tetrazoles theoretically can exist in the form of
`1-H- and 2-H-tautomers, it has been shown in many cases that the 1-H form is preferred.
`Thus the acidities of tetrazoles are actually estimated from the pKa values of the 1-H(cid:173)
`tautomers.
`The protonation of tetrazoles in aqueous solutions of sulfuric and perchloric acids is
`described by the H0 acidity function. Since the distribution of the electron density over
`the tetrazole ring has its maximum value on the 1 and 4 nitrogen atoms [3], the addition
`of a proton may lead to the formation of two tautomers. This possibility cannot be ex(cid:173)
`cluded during a study of the protonation of these compounds. Nevertheless, the available
`significant amount of experimental data on the basicities of tetrazoles with various struc(cid:173)
`tures [2] makes it possible to assume that the protonation center is the ring 3 atom. Below
`we present new data on the effect of the nature of the substituents attached to the ring
`carbon atom on the acidities and basicities of tetrazoles and we also discuss the inter(cid:173)
`relationship between the acidities and the basicities of these compounds.
`
`It has been previously shown that the acidities of substituted 5-phenyltetrazoles
`change only slightly, despite the wide variation in the electronic properties of the sub(cid:173)
`stituents [4]. The relatively low value of reaction constant p (1.27) constitutes evidence
`for the weak effect of the substituent attached to the ring carbon atom on the acidities of
`these compounds in water. A similar principle is observed during a study of the acidities
`of substituted 5-phenyltetrazoles in aqueous alcohol solutions and in the dimethyl sul(cid:173)
`foxide (DMSO)-water system [5].
`
`The reaction constants for the indicated solvents are, respectively, 1.52 and 1.67.
`At the same time, the dependence of the pKa values of acidic dissociation in water on the
`crp substituent constants for 5-R-tetrazoles (R = CH 3 ,* H*, Br, I, CF 3 , and NOz*) has
`the
`form
`
`pKa = - (6.65±0.60) <Jn + ( 4.46 ±0.27),
`r=0.98, n=6. s=0.5.
`It follows from this that in the acidic dissociation of substituted 5-phenyltetrazoles
`the phenyl ring isolates to a considerable extent the reaction center from the electronic
`effect of the substituent.
`In this case a quantitative measure of the bridging effect of the
`phenyl ring is transmission factor n' = 0.19 [9], which is calculated from the ratio of the
`reaction constants for acidic dissociation in water of substituted 5-phenyltetrazoles and
`5-R-tetrazoles.
`No less interesting information regarding the transmission of the electronic effects of
`substituents through the phenyl ring can evidently be obtained by a comparison of the
`basicity constants of substituted 5-phenyltetrazoles and 5-R-tetrazoles. The basicities of
`substituted 5-phenyltetrazoles depend relatively little on the nature of the substituents in
`the phenyl ring [10]. Thus the pKBH+ values of 5-(o-methylphenyl)- and 5-(p-nitrophenyl)(cid:173)
`tetrazoles are; respectively, -1.96 and -4.19. The reactivity constant p = 1.80 obtained
`from the dependence of the PKBH+ values of substituted 5-phenyltetrazoles on the cr sub(cid:173)
`stituent constants also constitutes evidence for the low sensitivity of protonation to the
`effect of the substituents. Since data on the basicities of 5-substituted tetrazoles that
`contain "simple" substituents are not available, for comparison with substituted 5-phenyl(cid:173)
`tetrazoles we selected a series of 5-R-tetrazoles, the protonation of which was studied in
`aqueous solutions of sulfuric acid by UV and PMR spectroscopy (Table 1). The basicity con(cid:173)
`stants of 5-R-tetrazoles were calculated from the expression
`+
`[TH]
`
`(1)
`
`log [ = -mHo+ pK BH+, where!= m·
`
`I
`
`For all of the investigated compounds slopes min Eq. (1) are close to unity (Table 1).
`Consequently, it may be assumed that 5-R-tetrazoles are protonated in the same way as Hammett
`bases and that the thermodynamic pKBH+ values can be obtained by division of the free term
`of Eq. (1) by slope m. The thermodynamic pKBH+ values of 5-R-tetrazoles correlate with the
`crp substituent constants:
`
`PKmr+=- (7.83±0.60)-an- (2.88±0.50),
`r=0.99, n=6, s=0.40.
`
`*The pKa values were obtained by the authors for individual compounds taken from [6-8].
`
`413
`
`

`
`Fig. 1. Dependence of the pKa and pHBH*
`values of 5-substituted tetrazoles: 1)
`5-methyltetrazole; 2) tetrazole; 3)
`5-(p-methoxyphenyl)tetrazole; 4) 5-(m(cid:173)
`chlorophenyl)tetrazole; 5) (m-nitro(cid:173)
`phenyl)tetrazole; 6) 5-(p-nitrophenyl)(cid:173)
`tetrazole; 7) 5-(o-nitrophenyl)tetrazole;
`8) 5-iodotetrazole; 9) 5-bromotetrazole;
`10) 5-trifluoromethyltetrazole; 11)
`5-nitrotetrazole.
`
`TABLE 1. Protonation of 5-R-Tetrazoles in Aqueous Solutions
`of H2S04 at 25°C
`Method of in-
`vestigation
`(A., nm)
`
`log f~-mlio+pK'Bn+
`
`m
`
`I
`
`-pK' mr+
`
`-pKnu+
`
`I
`
`I
`
`r
`
`!
`
`n
`
`I
`
`s
`
`R
`
`CHs
`H
`Br
`I
`CFs
`N02
`
`PMR
`PMR
`uv
`uv
`uv
`uv
`uv
`
`(200)
`(230)
`(210)
`(235)
`(240)
`
`0,93±0,02
`0,86±0,06
`0,91 ±0,06
`0,88±0,05
`0,90±0,02
`1,00±0,0$
`0,95±0,05
`
`1,60±0,04
`2,28±0,14
`4,72±0,30
`3,87±0,20
`6,30±0,14
`9,28±0,20
`9,28±0,22
`
`I ,83
`2,68
`5,20
`4,40
`7,00
`9,26
`
`0,99
`0,96
`0,99
`0,99
`0,97
`0,99
`0,99
`
`8
`19
`7
`7
`8
`8
`8
`
`O,o3
`0,13
`0,12
`0,10
`0,20
`0,13
`0,09
`
`TABLE 2. Protonation of Substituted Tetrazoles in Aqueous
`Solutions of H2S04 at 25°C
`Method of in-~
`vestigation
`I
`(A, nrr.)
`
`log I~-mHc+PK'nu+
`
`·-pK'mr+
`
`-nKnn+
`
`r
`
`n
`
`s
`
`I
`I
`10 I 0.04
`I 0.99
`I 0,99 I 10 I o.o6
`
`0,99
`0,97
`
`8
`7
`
`0,08
`0,17
`
`0,99
`
`8
`
`0,03
`
`R
`
`H
`CI-h
`N02
`
`H
`N02
`
`PMR
`PMR
`uv
`
`(240)
`
`PMR
`uv
`
`(245)
`
`m
`
`0,98±0,02 l 2,94±0,01
`0.91 ±0,03 I 2,96±0,10 !
`
`1-Methyl-5 -R-tetrazoles
`
`3,00
`1,6fl±0,07
`I ,68
`0,99±0,04
`8,84±0,60
`9,31
`0,95±0,10
`2-Methyl-5-R-tetrazoles
`3,25
`9,06
`
`8,97±0,19
`
`0,99±0,02
`
`Thus it is apparent that the pKBH+ value undergoes a change of seven orders of magni(cid:173)
`tude on passing from 5-methyl- to 5-nitrotetrazole. This circumstance may be associated
`either with a shift of the protonation center or with the electronic effect of the sub(cid:173)
`stituents.
`As we have already noted, tetrazoles with different structures, including substituted
`5-phenyltetrazoles, undergo protonation at the nitrogen atom in the 4 position of the ring
`in aqueous solutions of mineral acids. The correlation of the pKBH+ values of 5-R-tetrazoles
`with the Op substituent constants means that the addition of a proton to the tetrazole ring
`
`414
`
`

`
`for all of the members of the reaction series occurs at one and the same reaction center.
`However, on the basis of this one cannot answer the question as to which of the nitrogen
`atoms of the ring (1 or 4) is the protonation center. This information can be obtained by
`a comparison of the basicities of 5-R-tetrazoles and their 1- and 2-methyl-substituted de(cid:173)
`rivatives (Table 2). All of the compounds presented in Table 2 are Hammett bases.
`It is
`apparent (Tables 1 and 2) that 5-methyltetrazole is a stronger base than the isomeric
`1-methyl- and 2-methyltetrazoles, while 1,5-dimethyltetrazole differs virtually not at all
`from 5-methyltetrazole. The basicity constants of 5-nitrotetrazole and 1-methyl- and
`2-methyl-5-nitrotetrazoles are also very close to one another. A similar principle can be
`observed by comparing the basicities of 5-phenyltetrazole and 1-methyl- and 2-methyl-5-
`phenyltetrazoles [11].
`It follows from this that the addition of a proton to 5-R-tetra(cid:173)
`zoles, just as in the case of 5-phenyltetrazoles, takes place at the nitrogen atom in the
`4 position of the ring, since otherwise all 1-methyl- and 2-methyl-5-R-tetrazoles should be
`stronger bases than the corresponding 5-R-substituted compounds.
`On the basis of this, the reaction constants for protonation of substituted 5-phenyl(cid:173)
`tetrazoles and 5-R-tetrazoles can be used to calculate the transmission factor. The small
`transmission factor n' = 0.23 means that in the protonation, just as in acidic dissociation,
`of substituted 5-phenyltetrazoles the phenyl ring substantially insulates the reaction cen(cid:173)
`ter from the electronic effect of the substituent.
`Thus it is evident that the effect of substituents on the acidites and basicities of
`5-substituted tetrazoles is manifested in the same way and that a linear dependence should
`consequently exist between the pKa and pKBH+ values of these compounds.
`In fact, this sort
`of correlation does exist (see Fig. 1) and is described by the equation
`
`PKa= (0.78±0.05)pKmr++ (6.37±0.25), r=0.98, n=ll, s=0.3.
`It should be noted that expression (2) encompasses a rather broad range of changes in the
`pKa and pKB~ values, and this makes it possible to make a quantitative evaluation of the
`acid-base properties of 5-substituted tetrazoles with the most diverse structures.
`
`(2)
`
`EXPERIMENTAL
`The tetrazole and the disubstituted tetrazoles were obtained by known methods. All of
`the compounds had characteristics that were in agreement with the literature data [6-8, 12,
`13]. Aqueous buffer solutions with ionic strength v 0.01 were prepared by the method in
`[14]. The sulfuric acid solutions were obtained by dilution of 96% H2S0 4 (especially pure(cid:173)
`grade) with twice-distilled water, while solutions with higher concentrations were prepared
`by the addition of oleum (analytical-grade). The concentrations were determined by poten(cid:173)
`tiometric titration with a 0.1 N solution of NaOH with an accuracy of ±0.1%. The acidity
`constants of tetrazole (pKa = 4.86 ± 0.02) and 5-methyltetrazole (pKa = 5.50 ± 0.01) in
`water were determined by potentiometry in a thermostatted cell (25 ± O.l°C) with a pH-121
`pH meter. The acidity constants of 5-nitrotetrazole (pKa = -(),83 ±0.03) were determined
`spectrophotometrically in aqueous buffer solutions and aqueous solutions of sulfuric acid.
`During the study of the acidities and basicities of the tetrazoles the UV spectra were re(cid:173)
`corded with an SF-26 spectrophotometer with a thermostatted block (25 ± O.l°C); the
`analytical concentrations of the tetrazoles were ~1·10- 5 mole/liter. The PMR spectra were
`recorded with a Perkin-Elmer R-12 spectrometer; the analytical concentrations of the tetra(cid:173)
`zoles were ~1·10- 2 mole/liter, and the internal standard was tetramethylammonium bromide.
`The values of the Ho and H_ acidity functions were taken from [15, 16], The experimental
`data were processed by the methods presented in [4, 10].
`
`1.
`
`2.
`
`3.
`
`4.
`
`LITERATURE CITED
`V. A. Ostrovskii, G. I. Koldobskii, and I. Yu. Shirobokov, Zh. Org. Khim., !L, 146
`(1981).
`G. I. Koldobskii, V. A. Ostrovskii, and B. V. Gidaspov, Khim. Geterotsikl. Soedin.,
`No. 7, 867 (1980).
`V. A. Ostrovskii, N. S. Panina, G. I. Koldobskii, B. V. Gidaspov, and I. Yu. Shirobokov,
`Zh. Org. Khim., 15, 844 (1979).
`V. A. Ostrovskii, G. I. Koldobskii, N. P. Shirokova, I. Yu. Shirobokov, and B. V.
`Gidaspov, Zh. Org. Khim., 14, 1697 (1978).
`
`415
`
`

`
`5. J. Kaczmarek, H. Smagowski, and Z. Grzonka, J. Chern. Soc., Perkin II, No. 12, 1670
`(1979).
`6. J. S. Mihina and R. M. Herbst, J. Org. Chern., 12, 1082 (1950).
`7. E. Lieber, S. Patinkin, and H. H. Tao, J. Am. Chern. Soc., ]1, 1792 (1951).
`8. W. P. Norris, J. Org. Chern.,~. 3248 (1962).
`9. Yu. A. Zhdanov and V. I. Minkin, Correlation Analysis in Organic Chemistry [in Rus(cid:173)
`sian], Rostov-on-Don (1966), p. 56.
`10. V. N. Strel'tsova, N. P. Shirokova, G. I. Koldobskii, and B. V. Gidaspov, Zh. Org.
`Khim., 10, 1081 (1974).
`11. A. V. Moskvin, V. A. Ostrovskii, I. Yu. Shirobokov, G. I. Koldobskii, and B. V.
`Gidaspov, Zh. Org. Khim., 14, 2440 (1978).
`12. R. A. Henry and W. G. Finnegan, J. Am. Chern. Soc., 76, 290 (1954).
`13. R. A. Henry and W. G. Finnegan, J. Am. Chern. Soc., 76, 923 (1954).
`14. D. D. Perrin, Aust. J. Chern., 16, 572 (1963).
`15. M. I. Vinnik, Usp. Khim., 35, 1922 (1966).
`16. R. H. Boyd, J. Am. Chern. Soc., 83, 4288 (1961).
`
`416