A STUDY OF TRANSMISSION EFFECTS OF SULFONYL AND CARBONYL GROUPS

Article abstract of DOI:10.1135/cccc19950841

Seventeen p-substituted N-phenylsulfonylbenzamides of general formulas XC6H4SO2NHCOC6H5 and C6H5SO2NHCOC6H4X have been synthesized and their structure has been confirmed by elemental analysis and 1H NMR spectra.The dissociation constants of all compounds have been measured by potentiometric titration in methanol, acetonitrile, dimethylformamide, dimethyl sulfoxide, and pyridine.The obtained pK_HA values have been correlated with three sets of Hammett substituent constants using simple or double linear regression.The solvent and substituent effects are discussed on the basis of experimental results, and the difference between the substituent effects from sulfonamide and benzamide sections is evaluated.It has been found that due to extensive delocalization of negative charge in the conjugated base the transmission effects of carbonyl and sulfonyl groups on the transmission of substituent effect are roughly the same.The experimental data have been interpreted by the methods with latent variables: the principal component analysis (PCA), the conjugated deviation analysis (CDA), and the method of projection to latent structures (PLS).The results obtained by these procedures were similar.

Full text of DOI:10.1135/cccc19950841

Transmission Effects of Sulfonyl and Carbonyl Groups
841
A STUDY OF TRANSMISSION EFFECTS OF SULFONYL
AND CARBONYL GROUPS
Miroslav LUDWIG, Patrik PARIK and Jiri KULHANEK
Department of Organic Chemistry,
University of Pardubice, 532 10 Pardubice, The Czech Republic
Received December 23, 1994
Accepted February 15, 1995
Seventeen p-substituted N-phenylsulfonylbenzamides of general formulas XC6H4SO2NHCOC6H5 and
C6H5SO2NHCOC6H4X have been synthesized and their structure has been confirmed by elemental
1
analysis and H NMR spectra. The dissociation constants of all the compounds have been measured
by potentiometric titration in methanol, acetonitrile, dimethylformamide, dimethyl sulfoxide, and
pyridine. The obtained pKHA values have been correlated with three sets of Hammett substituent
constants using simple or double linear regression. The solvent and substituent effects are discussed
on the basis of experimental results, and the difference between the substituent effects from
sulfonamide and benzamide sections is evaluated. It has been found that due to the extensive
delocalization of negative charge in the conjugated base the transmission effects of carbonyl and
sulfonyl groups on the transmission of substituent effect are roughly the same. The experimental data
have been interpreted by the methods with latent variables: the principal component analysis (PCA),
the conjugated deviation analysis (CDA), and the method of projection to latent structures (PLS). The
results obtained by these procedures were similar.
The basic model process used by Hammett1 in his studies of substituent effects in
benzene nucleus was dissociation of substituted benzoic acids in water. Obviously, the
substituent and solvent effects upon dissociation can be studied with other types of
substrates such as various aromatic O-, N-, and C-acids and with other media. Such a
substrate is, e.g., N-phenylsulfonylbenzamide with substituents at para position of
benzenesulfonamide ring (type A) or at para position of benzamide ring (type B).
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Ludwig, Parik, Kulhanek:
These compounds offer a model for studying two types of substituent effects. In one
case the reaction centre is affected by the substituent through aromatic ring and
sulfonyl group, and in the other case through aromatic system and carbonyl group. The
substitution at para position was chosen because the substituent effect from this
position is more complex than that from the nonalternating meta position2.
The dissociation of N-phenylsulfonylbenzamides has been studied several times
experimentally, however, mostly within the framework of another reaction series.
These studies involve the determination of dissociation constants of acylated
benzenesulfonamides C6H5SO2NHR (R = COCH3, COCH2Cl, COCHCl2, CONHCN,
CH2COOH, COC6H5, CSC6H5, COC6H4Cl, and CONHC6H5) in acetone and cyclo-
hexanone3, in anisole, butyl acetate, tributyl phosphate, and dibutyl ether–anisole mixture4,
and finally in 1-butanol, isobutyl alcohol, tert-butyl alcohol, cyclohexanol, acetone, and
anisole5. A series of five N-phenylsulfonylbenzamides p-XC6H4CONHSO2C6H5
(X = NH2, H, CH3, OCH3, and NO2) was measured6 in 60% aqueous dioxane. The
largest data set was provided by measurements7 of dissociation constants of
p-substituted N-phenylsulfonylbenzamides p-XC6H4SO2NHCOC6H4Y-p (X = H, Cl, CH3,
NO2, NH2, Br, and Y = NO2, Cl, Br).
The chief aims of the present work are to compare the substituent effects from the
two nuclei of model substrates upon the value of dissociation constants, to study the
transmission of substituent effects through the sulfonyl and carbonyl groups on the
imide nitrogen atom and, as the case may be, the substituent effect upon the massive
delocalization of negative charge in the conjugated base, and to discuss the solvent
effect upon the effects mentioned. The paper forms a continuation of former
contributions dealing with dissociation of various sulfonamides8–11
.
EXPERIMENTAL
The 1H NMR spectra of the model compounds prepared were measured on a Bruker AMX 360
apparatus using their 5% solutions in (CD3)2SO and the chemical shifts were referenced to the
solvent signal. The pKHA values of the imides type A and B were determined in methanol (MeOH),
acetonitrile (AN), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and pyridine (Py)
using potentiometric titration on an automatic titrator Radiometer RTS-622 using the same electrode
arrangement and titration reagent as those in earlier papers8–11. The solvents used were purified in
standard way.
Synthesis of p-Substituted N-Phenylsulfonylbenzamides
The synthesis of model substrates was carried out by procedures analogous to those given in
literature: alkaline fusion of corresponding benzenesulfonamides with phenyl benzoates12 or, in the
case of preparation of N-benzoyl-p-toluenesulfonamide, reaction of p-toluenesulfonamide with
benzoyl chloride13. The starting phenyl benzoates were prepared by reaction of substituted benzoyl
chlorides with phenoxide14 or by reaction15 of substituted benzoic acids with phenol and POCl3. The
substituted benzoyl chlorides were prepared from corresponding benzoic acids by a reaction with
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Transmission Effects of Sulfonyl and Carbonyl Groups
843
SOCl2 catalyzed with DMF (ref.16). The benzoic acids and benzenesulfonamides used were prepared
by known procedures.
Alkali Fusion of Benzenesulfonamides with Phenyl Benzoates (modified ref.12)
A 100 ml flask equipped with reflux condenser was charged with a mixture of 0.02 mol respective
benzenesulfonamide, 0.02 mol respective phenyl benzoate, and potassium carbonate (1.2 g, 0.12 mol),
and the content was fused on a wire gauze 15 – 20 min. After cooling, the reaction mixture was
dissolved in 5% aqueous sodium carbonate (200 ml), filtered, and extracted with benzene (2 × 100 ml).
The alkaline solution was acidified with diluted hydrochloric acid (100 ml) to pH 1 (to pH 2 for
N-benzenesulfonyl-p-dimethylaminobenzamide solution) and the separated solid was collected by
filtration. If much contaminated, the imide was reprecipitated from carbonate solution by adding
dilute hydrochloric acid. Finally, the product was recrystallized from ethanol or toluene until constant
melting point. Table I presents the starting materials, melting points and yields of the products
synthesized. The elemental analyses carried out for the known compounds agreed with the calculated
values.
RESULTS AND DISCUSSION
Table II presents the chemical shifts of all the model derivatives of N-benzene-
sulfonylbenzamides prepared. The chemical shifts of acidic proton are not given since
their signals were mostly very broad. The values of dissociation constants of the
individual model substrates in individual solvents are given as average values pKHA
(with standard deviations) in Table III. The solvents were selected with the aim of
covering the main types of solvents commonly used for titrations: amphiprotic
methanol, dipolar aprotic protophobic acetonitrile, dipolar aprotic protophilic
N,N-dimethylformamide, dimethyl sulfoxide, and pyridine. The substituents chosen can
be classified as ones without any distinct mesomeric effect (CH3, H, Cl, Br), those with
positive mesomeric effects (NH2, N(CH3)2, OCH3, F), and those with negative
mesomeric effects (CN, NO2). The experimental results obtained were treated by
several mathematical-statistical methods. For the treatment of results by simple and
double linear regression analysis we always used all the experimental points found
(each experiment was repeated four times). For the methods working with latent
variables – the principal component analysis (PCA, ref.20), conjugated deviations
analysis (CDA, ref.21), and projection of latent structures (PLS, ref.22) we used the
___
average pKHA values.
The classical treatment of results according to the original Hammett relation involved
ten regressions, i.e. five linear regressions for the A series and the same number for B.
The calculations were carried out with application of three sets of substituent constants,
viz. σp (ref.23), σP6, and σF6 (ref.24). A closer fit is obtained with the σP6 and σF6
constants, which can be due to the fact that these constants were defined on the basis of
data describing the dissociation of benzoic acid in nonaqueous media. However, from
the definition of the Hammett relation it follows that the pK0 values should be the same
for the two series A, B, in a given solvent. The result of testing the hypotheses of
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Collect. Czech. Chem. Commun. (Vol. 60) (1995)