Ortho effect in dissociation of substituted N-phenylbenzenesulfonamides

Article abstract of DOI:10.1135/cccc20011380

Twenty-five 2,2′-disubstituted N-phenylbenzenesulfonamides (2-X-C₆H₄SO₂NHC₆H₄-Y-Z′) were synthesised and their purity checked by elemental analysis. This set of model substrates involved all possible combinations of methoxy, methyl, hydrogen, chloro, and nitro substituents. The dissociation constants of the sulfonamides were determined by potentiometric titration in methanol, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, acetone, and acetonitrile. The dissociation constants pKHA obtained were correlated with various sets of substituent constants describing electronic and steric effects of the substituents, and the statistically treated data were used to discuss the contribution of the substituent effects in the dissociation and the difference between the effects transmitted from the two rings. A linear regression model explaining 99% of the variability of experimental data in all the solvents has been found and discussed. Moreover, the experimental data were also interpreted by the methods using latent variables, the principal component analysis (PCA) and conjugated deviation analysis (CDA), and two latent variables were shown to be statistically significant in the description of dissociation. The first obviously describes common action of electronic and steric effects of substituents; the other probably concerns a combined effect of substituent and solvent on the position of acid-base equilibrium.

Full text of DOI:10.1135/cccc20011380

1380
Nádvorník, Ludwig:
Ortho EFFECT IN DISSOCIATION OF SUBSTITUTED
N-PHENYLBENZENESULFONAMIDES
1
2,
Jiří NÁDVORNÍK and Miroslav LUDWIG *
Department of Organic Chemistry, Faculty of Chemical Technology, University of Pardubice,
1
nám.Čs.legií 565, CZ-532 10 Pardubice, Czech Republic; e-mail:
miroslav.ludwig@upce.cz
jiri.nadvornik@upce.cz,
2
Received March 29, 2001
Accepted May 18, 2001
Twen ty-five 2,2′-disubstituted N-ph en ylben zen esulfon am ides (2-X-C6H4SO2NHC6H4-Y-2′)
were syn th esised an d th eir purity ch ecked by elem en tal an alysis. Th is set of m odel sub-
strates in volved all possible com bin ation s of m eth oxy, m eth yl, h ydrogen , ch loro, an d n itro
substituen ts. Th e dissociation con stan ts of th e sulfon am ides were determ in ed by
poten tiom etric titration in m eth an ol, pyridin e, dim eth yl sulfoxide, N,N-dim eth ylform am ide,
aceton e, an d aceton itrile. Th e dissociation con stan ts pKHA obtain ed were correlated with
various sets of substituen t con stan ts describin g electron ic an d steric effects of th e substitu-
en ts, an d th e statistically treated data were used to discuss th e con tribution of th e
substituen t effects in th e dissociation an d th e differen ce between th e effects tran sm itted
from th e two rin gs. A lin ear regression m odel explain in g 99% of th e variability of experi-
m en tal data in all th e solven ts h as been foun d an d discussed. Moreover, th e experim en tal
data were also in terpreted by th e m eth ods usin g laten t variables, th e prin cipal com pon en t
an alysis (PCA) an d con jugated deviation an alysis (CDA), an d two laten t variables were
sh own to be statistically sign ifican t in th e description of dissociation . Th e first obviously de-
scribes com m on action of electron ic an d steric effects of substituen ts; th e oth er probably
con cern s a com bin ed effect of substituen t an d solven t on th e position of acid-base equilib-
rium .
Keyw ord s: Sulfon am ides; Dissociation con stan ts; Ortho effect; Ch em om etrics; Substituen t
effects; Solven t effects.
Ortho effect is a very in terestin g ph en om en on in th e th eory of substituen t
effects because in teraction s between a reaction cen tre an d ortho substitu-
en ts are m ediated n ot on ly by σ an d π bon ds of th e ben zen e rin g (as it is
th e case with meta an d para substituen ts) but som e furth er effects also be-
com e eviden t; am on g th em , th e m ost sign ifican t are steric effects an d, as
th e case m ay be, form ation of in tram olecular h ydrogen bon d between th e
ortho substituen t an d reaction cen tre. N-Ph en ylben zen esulfon am ides 1 with
ortho substituen ts in both rin gs are possible m odels for studyin g th e ortho
effect: determ in ation of th eir dissociation con stan ts in various organ ic sol-
Collect. Czech. Chem. Commun. (Vol. 66) (2001)
doi:10.1135/cccc20011380

Substituted N-Phenylbenzenesulfonamides
1381
ven ts provides – relatively easily – a large body of data th at can be treated
statistically to give in form ation about effects operatin g in th e dissociation
of th ese com poun ds.
Th e m en tion ed m odel was ch osen due to th e presen ce of th e two ben -
zen e rin gs: th eir respective ortho substituen ts affect th e reaction cen tre in
differen t ways because th e distan ces from th e reaction cen tre are differen t.
In addition , form ation of a h ydrogen bon d is possible between th e acid h y-
drogen of th e SO2NH groupin g an d som e of th e substituen ts; som e of th e
ortho substituen ts of th e NHPh m oiety can be directly con jugated with th e
reaction cen tre.
Th e dissociation of N-ph en ylben zen esulfon am ides with at least on e
substituent in the ortho position of one of the two rings almost has not been
studied yet; if it was, then only within a series involving also substituents at the
meta or para positions. In such cases, the values of dissociation constants of
ortho derivatives were discussed only qualitatively, namely as an acidity increase
or decrease in comparison with the corresponding meta and para substituted
substrates. Potentiometric titration was used to find the dissociation constants
of com pounds of the 2-X-C6H4SO2NHC6H5 and C6H5SO2NHC6H4-Y-2′ types
(X = NO 2, Y = CH3, O CH3, NO 2) in 72% aq u eo u s et h an o l1,2, an d co m -
p o u n d s o f t h e 4 -R1 -3 -R2 -C 6 H 3 SO 2 N H C 6 -2 ′-R3 -6 ′-R4 -3 ′-R5 -5 ′-R6 -4 ′-R7
(R3 an d R4 = CH3 or Cl) in 50% aqueous eth an ol3. Spectroph otom etry was
used to determ in e th e dissociation con stan ts of substan ces of th e
C6H5SO2NHC6H4-Y-2′ type (Y = OCH3, CH3, CH3OCO, Cl, Br, NO2) in
X
Y
O
S
H
N
O
1
a
b
c
d
e
f
g
h
i
X
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
OCH3
OCH3
OCH3
Y
H
CH3
OCH3
Cl
NO2
H
CH3
OCH3
Cl
NO2
H
1
n
o
p
q
r
X
Y
Cl
OCH3
OCH3
Cl
Cl
Cl
NO2
H
CH3
OCH3
Cl
NO2
H
CH3
OCH3
Cl
s
t
Cl
Cl
u
v
w
x
y
NO2
NO2
NO2
NO2
NO2
j
k
l
CH3
OCH3
NO2
m
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1382
Nádvorník, Ludwig:
dim eth yl sulfoxide4, th e values foun d bein g correlated with on e of th e pro-
posed sets of σortho con stan ts.
EXPERIMENTAL
Syn th eses of In term ediates an d Model Substan ces
Th e m odel substan ces were prepared by reaction s of th e correspon din g 2-substituted
ben zen esulfon yl ch lorides with 2-substituted an ilin es5. Th e reaction yields are given below.
Th e respective ben zen esulfon yl ch lorides were obtain ed by decom position of
ben zen ediazon ium salts in acetic acid saturated with sulfur dioxide in th e presen ce of
Cu2Cl2 (ref.6). Th e purity of all th e sulfon am ides prepared was ch ecked by elem en tal an aly-
sis usin g an autom atic an alyser EA 1108 (Fison s).
N-Ph en ylben zen esulfon am ides of Gen eral Form ula 2-X-C6H4SO2NHC6H4-Y-2′
4
4
1a: Yield 49%, m .p. 105–107 °C (ref. 107–109 °C). 1b: Yield 86%, m .p. 119–121 °C (ref.
124–126 °C). 1c: Yield 51%, m .p. 82.5–83.5 (ref. 4 85–86 °C). 1d : Yield 83%, m .p. 125–126 °C
(ref.4 129–130 °C). 1e: Yield 62%, m .p. 96–96.5 °C (ref. 99–101 °C). 1f: Yield 35%, m .p.
132–133.5 °C (ref. 136 °C). 1g: Yield 41%, m .p. 113–115 °C (ref. 134 °C). 1h : Yield 48%,
m .p. 102.5–103.5 °C. For C 14H15NO3S (277.3) calculated: 60.63% C, 5.45% H, 5.05% N,
11.56% S; foun d: 60.11% C, 5.51% H, 5.98% N, 11.29% S. 1i: Yield 36%, m .p. 76–77 °C. For
4
7
8
C
13H12ClNO2S (281.8) calculated: 55.42% C, 4.29% H, 4.97% N, 11.38% S; found: 55.08% C,
4.35% H, 5.82% N, 11.12% S. 1j: Yield 33%, m .p. 95.5–98 °C. For C 13H12N2O4S (292.3) calcu-
lated: 53.42% C, 4.14% H, 9.58% N, 10.97% S; foun d: 53.48% C, 4.23% H, 9.82% N, 10.52% S.
9
1k : Yield 58%, m .p. 154.5–156 °C (ref. 161 °C). 1l: Yield 59%, m .p. 144–145 °C. For
C
14H15NO3S (277.3) calculated: 60.63% C, 5.45% H, 5.05% N, 11.56% S; foun d: 60.64% C,
5.41% H, 5.42% N, 10.87% S. 1m : Yield 28%, m.p. 94–95 °C. For C 14H15NO4S (293.3) calculated:
57.32% C, 5.15% H, 4.77% N, 10.93% S; foun d: 57.47% C, 5.18% H, 5.20% N, 10.06% S. 1n :
Yield 31%, m .p. 116.5–117.5 °C. For C 13H12ClNO3S (297.8) calculated: 52.44% C, 4.06% H,
4.70% N, 10.77% S; foun d: 52.33% C, 4.10% H, 5.01% N, 10.23% S. 1o: Yield 53%, m .p.
120.5–121.5 °C. For C 13H12N2O5S (308.3) calculated: 50.65% C, 3.92% H, 9.09% N, 10.40% S;
foun d: 50.67% C, 3.99% H, 9.35% N, 9.90% S. 1p : Yield 52%, m .p. 141.5–143 °C. For
C
12H10ClNO2S (267.7) calculated: 53.84% C, 3.76% H, 5.23% N, 11.97% S; found: 53.78% C,
3.75% H, 5.25% N, 11.07% S. 1q: Yield 45%, m .p. 119–121 °C. For C 13H12ClNO2S (281.8) cal-
culated: 55.42% C, 4.29% H, 4.97% N, 11.38% S; foun d: 55.57% C, 4.42% H, 4.96% N,
10.31% S. 1r: Yield 43%, m .p. 91–92 °C. For C 13H12ClNO3S (297.8) calculated: 52.44% C,
4.06% H, 4.70% N, 10.77% S; foun d: 52.34% C, 4.02% H, 4.73% N, 9.70% S. 1s: Yield 38%,
m .p. 89–90 °C. For C 12H9Cl2NO2S (302.2) calculated: 47.70% C, 3.00% H, 4.64% N, 10.61% S;
foun d: 47.72% C, 2.87% H, 4.67% N, 9.76% S. 1t: Yield 34%, m .p. 125.5–126.5 °C. For
C
12H9ClN2O4S (312.7) calculated: 46.09% C, 2.90% H, 8.96% N, 10.25% S; found: 45.98% C,
10
2.80% H, 8.97% N, 9.43% S. 1u: Yield 22%, m .p. 110–111 °C (ref.
m .p. 133–134 °C (ref. 137–138 °C). 1w: Yield 64%, m .p. 87.5–88.5 °C (ref. 91–92 °C). 1x:
Yield 65%, m .p. 143–144 °C (ref. 147–148 °C). 1y: Yield 34%, m .p. 139–140 °C. For
114–115 °C). 1v: Yield 69%,
5
5
5
C
12H9N3O6S (323.3) calculated: 44.58% C, 2.81% H, 13.00% N, 9.92% S; foun d: 44.39% C,
2.88% H, 13.07% N, 10.25% S.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Substituted N-Phenylbenzenesulfonamides
1383
Poten tiom etric Titration s
Th e dissociation con stan ts of sulfon am ides (pKHA) at 25 °C in m eth an ol (MeOH), dim eth yl
sulfoxide (DMSO), N,N-dim eth ylform am ide (DMF), aceton e (Me2CO), aceton itrile (AN), an d
pyridin e (Py) were determ in ed by poten tiom etric titration usin g an autom atic apparatus
Titralab 3 (Radiom eter), th e electrodes an d experim en tal arran gem en t bein g th e sam e as in
th e previous studies11–13 . Each m easurem en t was repeated th ree to four tim es. Th e solven ts
used were purified in stan dard way.
RESULTS AND DISCUSSION
Table I sum m arises th e m ean values of dissociation con stan ts in th e form of
pKHA alon g with th e correspon din g stan dard deviation s for th e in dividual
com poun ds an d solven ts.
Th e experim en tal data obtain ed were subjected to statistical treatm en t.
All th e pKHA values were used in calculation s of m ultiple lin ear regression ,
an d th e m ean pKHA values were treated with th e m eth ods workin g with la-
ten t variables (PCA (ref.14) an d CDA (ref.15)).
Evaluation of Measured Data by Multiple Linear Regression
Th e explain in g variables in th e m ultiple lin ear regression were represen ted
by various com bin ation s of sets of substituen t con stan ts separately treatin g
th e electron ic an d steric effects. Th e electron ic effects were described by th e
followin g series of substituen t con stan ts: σ io (ref.16), σp (ref.17), an d σR to-
geth er with σI (ref.18). Th e steric effects were described by th e followin g
substituen t con stan ts: σ iS (ref.16) an d υ (ref.18). Th e regression param eters ρef
were calculated sim ultan eously for both groups of substituen ts (X an d Y)
from Eq. (1), wh ere σef are th e substituen t con stan ts (selected for th e regres-
sion ) describin g th e respective substituen t effect.
pKHA = pK0 +
ρXef σ Xef
+
ρYef σ Yef
(1)
∑
∑
Based on th e values of residual stan dard deviation an d th e m agn itude of
explain ed variability, th e best m odel is th at in cludin g th e σI, σR, an d σ i
S
con stan ts. Th is m odel explain s th e total variability of data as follows (resid-
ual stan dard deviation an d solven t are given in paren th eses): 98.6% (0.134,
MeOH), 99.0% (0.158, DMSO), 99.0% (0.170, DMF), 99.4% (0.136, Py),
99.6% (0.112, Me2CO), 99.2% (0.136, AN). However, a m ore detailed an aly-
sis of th is m odel sh ows a certain h eterogen eity of th e reaction con stan ts
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1384
Nádvorník, Ludwig:
TABLE I
Mean values of dissociation con stan ts in th e form of pKHA an d th eir stan dard deviation s (s)
of substituted N-ph en ylben zen esulfon am ides of gen eral form ula 2-X-C6H4SO2NHC6H4-Y-2′
Com p.
MeOH
DMSO
DMF
Py
Me2CO
AN
1a
1b
1c
1d
1e
1f
13.26 (0.09) 12.01 (0.05) 13.25 (0.04) 10.00 (0.06) 19.95 (0.08) 22.50 (0.03)
13.43 (0.12) 11.84 (0.11) 12.96 (0.04) 10.03 (0.18) 19.98 (0.10) 22.65 (0.05)
13.75 (0.04) 12.28 (0.06) 13.73 (0.09) 11.13 (0.12) 21.23 (0.03) 23.49 (0.11)
12.40 (0.08) 10.34 (0.11) 11.54 (0.03)
11.20 (0.01) 8.72 (0.14) 9.95 (0.06)
8.98 (0.02) 18.67 (0.01) 21.38 (0.01)
7.29 (0.03) 17.22 (0.01) 20.14 (0.06)
13.29 (0.05) 11.97 (0.07) 13.12 (0.05) 10.10 (0.02) 19.87 (0.06) 22.49 (0.07)
13.49 (0.08) 11.78 (0.05) 13.04 (0.06) 9.85 (0.02) 19.77 (0.11) 22.45 (0.09)
13.88 (0.10) 12.14 (0.11) 13.42 (0.04) 11.02 (0.07) 21.16 (0.08) 23.56 (0.07)
1g
1h
1i
12.40 (0.04) 10.04 (0.09) 11.42 (0.06)
11.22 (0.02) 8.35 (0.12) 9.56 (0.04)
8.82 (0.03) 18.50 (0.04) 21.27 (0.03)
7.15 (0.02) 17.03 (0.02) 20.07 (0.03)
1j
1k
1l
13.79 (0.10) 12.61 (0.12) 13.95 (0.09) 11.54 (0.02) 21.50 (0.19) 23.77 (0.11)
13.96 (0.05) 12.51 (0.16) 13.78 (0.07) 11.31 (0.19) 21.56 (0.14) 23.82 (0.08)
14.06 (0.06) 12.81 (0.21) 14.82 (0.12) 12.96 (0.01) 23.21 (0.12) 25.15 (0.06)
13.21 (0.07) 11.14 (0.01) 12.73 (0.04) 10.26 (0.04) 20.41 (0.03) 22.75 (0.04)
1m
1n
1o
1p
1q
1r
12.61 (0.06)
9.76 (0.10) 11.36 (0.05)
8.91 (0.03) 19.15 (0.02) 21.73 (0.01)
9.94 (0.04) 19.62 (0.07) 22.19 (0.05)
9.67 (0.06) 19.52 (0.07) 22.13 (0.03)
13.01 (0.08) 11.48 (0.15) 12.79 (0.04)
13.11 (0.07) 11.18 (0.06) 12.51 (0.04)
13.62 (0.04) 11.79 (0.06) 13.32 (0.19) 10.86 (0.08) 20.99 (0.06) 23.23 (0.02)
1s
1t
12.01 (0.04)
10.96 (0.01)
9.64 (0.08) 10.85 (0.06)
8.08 (0.08) 9.11 (0.14)
8.45 (0.03) 18.12 (0.01) 20.86 (0.04)
6.74 (0.03) 16.76 (0.02) 19.69 (0.06)
8.86 (0.03) 18.50 (0.03) 21.21 (0.05)
8.79 (0.02) 18.56 (0.03) 21.30 (0.03)
9.83 (0.02) 19.87 (0.06) 22.28 (0.04)
7.31 (0.04) 17.01 (0.01) 19.81 (0.02)
5.57 (0.06) 15.48 (0.07) 18.46 (0.03)
1u
1v
1w
1x
1y
12.14 (0.13) 10.43 (0.02) 11.69 (0.06)
12.39 (0.07) 10.21 (0.08) 11.52 (0.04)
12.91 (0.09) 10.78 (0.09) 12.34 (0.02)
11.08 (0.05)
10.04 (0.01)
8.53 (0.04)
6.90 (0.08)
9.74 (0.10)
8.32 (0.13)
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Substituted N-Phenylbenzenesulfonamides
1385
calculated (Table II). Th e first th in g to be n oticed is a n egative value of ρIX
in MeOH an d DMSO an d a positive value in Py, Me2CO, an d AN. A positive
value of th e con stan t m ean s th at electron -with drawin g (–I type) substitu -
en ts decrease th e acidity. Th is is on ly possible if th e substituen t does n ot af-
fect th e reaction cen tre by polarisation of σ bon ds but directly th rough
space. However, th e fact th at th e con stan t is n egative in som e solven ts an d
positive in oth ers m ay also be due to th e sm all n um ber of substituen ts in -
vestigated or, as th e case m ay be, to som e relation s between th e explain in g
variables. A potential inadequacy of the model is also indicated by the statistical
insignificance of the constant in DMF, which alone is surprising. In the model
discussed, th e statistically sign ifican t con stan ts are ρXS an d ρSY which quan-
tify the steric effects of substituents. Both these constants are negative in all
th e solven ts. Hen ce, th e sterically m ore dem an din g substituen ts in crease
th e acidity. In th is case, en tropy effects can play a role, e.g. a greater ch an ge
in solvation of th e species presen t on both sides of th e dissociation equilib-
rium an d carryin g bulky substituen ts. It is also possible to discuss th e differ-
en ces between th e substituen t effects tran sm itted to th e reaction cen tre
from th e two differen t rin gs, an d th e m an ifestation of in dividual effects
com in g from on e of th e rin gs. For th is purpose it is h elpful to calculate
som e ratios of th e reaction con stan ts (Table III). Th e ratios ρXR /ρIX an d ρRY /ρIY
expressin g th e relative m agn itudes of m esom eric an d in ductive effects in
each of th e rin gs are ch aracterised by an exten sive scatterin g of values. Th e
TABLE II
Reaction con stan ts an d th eir stan dard deviation s (s) obtain ed by regression of pKHA values
versus substituen t con stan ts σI, σR, an d σ Si
Solven t
ρXI
ρYI
ρXR
ρYR
ρXS
ρYS
MeOH
DMSO
DMF
Py
–0.77 (0.13) –1.84 (0.13) –2.63 (0.13) –3.78 (0.32) –1.91 (0.28) –3.12 (0.27)
–0.43 (0.15) –2.30 (0.15) –4.32 (0.14) –5.29 (0.15) –4.37 (0.32) –5.91 (0.32)
Na
–2.10 (0.16) –4.77 (0.13) –6.10 (0.15) –5.19 (0.16) –6.63 (0.34)
0.82 (0.13) –1.26 (0.13) –6.28 (0.14) –6.80 (0.13) –6.82 (0.28) –7.24 (0.28)
1.19 (0.13) –0.54 (0.13) –7.18 (0.13) –7.52 (0.12) –8.10 (0.28) –8.83 (0.28)
0.54 (0.13) –0.72 (0.13) –5.76 (0.12) –6.21 (0.12) –6.23 (0.28) –7.10 (0.28)
Me2CO
AN
a
N den otes a statistically in sign ifican t param eter.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1386
Nádvorník, Ludwig:
lowest an d n ot very differin g values are th ose foun d in m eth an ol, wh ereas
th ose foun d in th e oth er solven ts con siderably differ, it seem s th at th ese
values result from a specificity of th is m ath em atical m odel rath er th an th ey
reflect real properties of th e system . Th e ρYR /ρRX values are greater th an un ity
in all th e solven ts. Th e sen sitivity of th e dissociation to m esom eric effect of
substituen ts Y is th us stron ger th an th at of X substituen ts (as expected).
Th e sam e statem en t regardin g th e ratio ρYR /ρRX is also true for th e ρYS /ρSX ratio,
wh ich com pares th e steric effects of substituen ts in both th e position s.
Again , th e values of th e ρYI /ρIX con siderably differ an d are difficult to dis-
cuss. In con clusion , it can be stated th at th is m odel can n ot be con sidered
good (despite its ability to describe th e overall variability of data to a con -
siderable exten t) because th e values of regression coefficien ts obtain ed from
m ultiple lin ear regression are h ard to in terpret. Th is can be caused by th e
above-m en tion ed n arrow selection of substituen ts or by in volvem en t too
m an y variables in th e regression , wh ich were in addition , adjusted in en -
tirely differen t ways.
Lin ear regression s with oth er com bin ation s of substituen t con stan ts de-
scribin g electron ic an d steric effects of substituen ts gave substan tially worse
results with regard to th e calculated statistical ch aracteristics. Moreover, re-
gression param eters expressin g th e m an ifestation s of steric effects are statis-
tically in sign ifican t in m an y cases; h en ce it is im possible to un am biguously
claim th at th e dissociation is really sterically affected by th e substituen ts.
Th e m ultiple lin ear regression s in volvin g on ly th ose sets of substituen t
con stan ts th at describe th e electron ic effects of substituen ts will give in for-
TABLE III
Various ratios of reaction con stan ts obtain ed by regression of pKHA values versus th e
substituen t con stan ts σI, σR, an d σ Si
Solven t
ρYS /ρXS
ρYI /ρXI
ρYR/ρXR
ρXR/ρXI
ρYR/ρYI
MeOH
DMSO
DMF
Py
1.63
1.35
1.28
1.06
1.09
1.14
2.39
5.35
–
1.44
1.22
1.28
1.08
1.05
1.08
3.42
10.05
–
2.05
2.30
2.90
5.40
–1.54
–0.45
–1.33
–7.66
–6.03
–10.67
Me2CO
AN
–13.93
8.63
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Substituted N-Phenylbenzenesulfonamides
1387
m ation about th e exten t of m an ifestation of th ese effects in th e dissocia-
tion of m odel com poun ds. Table IV sum m arises th e correlation coefficien ts
an d residual stan dard deviation s calculated in th ese regression s.
Th e values of correlation coefficien ts R given in Table IV sh ow th at a
large part of data variability can be explain ed with th e h elp of th e
substituen t con stan ts describin g th e electron ic effects of substituen ts. Nev-
erth eless, th e un explain ed part of th em is by n o m ean s n egligible an d m ust
be ascribed to oth er effects. Th e average explain ed variability for each m e-
dium sh ows th e exten t to wh ich th e pKHA values are affected by electron ic
effects of substituen ts an d wh at part of total variability is due to oth er ef-
fects (an d, of course, to experim en tal error). If for each solven t th e used
m odels are arran ged in th e order of m agn itude of residual stan dard devia-
tion , it becom es clear th at th e ch oice of a set of substituen t con stan ts de-
scribin g th e electron ic effects of substituen ts for th e purpose of explan ation
of overall variability of data is n ot im m aterial (th is con clusion is based on
th e Friedm an test). Th e average order expressin g th e success of a m odel us-
in g particular substituen t con stan ts is as follows: σp 1.16, σ io 2.33, an d σI, σR
2.5. Th ese data m ake it clear th at th e largest part of overall variability is de-
scribed by th e m odel usin g th e σp con stan ts, th ere bein g n o differen ce be-
tween th e rem ain in g two m odels. In th e m odels usin g th e σp an d σ oi
con stan ts as explain in g variables, it is possible to observe (as could be ex-
pected) a larger effect on th e pKHA value of th e substituen ts Y, wh ich is ex-
TABLE IV
Correlation coefficien ts an d residual stan dard deviation s calculated from th e regression of
pKHA values versus various sets of substituen t con stan ts describin g electron ic effects
σp
σ oi
σI an d σR
Solven t
R
s
R
s
R
s
MeOH
DMSO
DMF
Py
0.967
0.965
0.959
0.950
0.930
0.943
0.278
0.422
0.473
0.536
0.664
0.507
0.958
0.974
0.958
0.929
0.902
0.920
0.311
0.364
0.480
0.632
0.779
0.596
0.956
0.961
0.946
0.939
0.919
0.929
0.325
0.451
0.551
0.594
0.724
0.571
Me2CO
AN
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1388
Nádvorník, Ludwig:
pressed by a greater absolute value of ρY con stan t as com pared with ρX
con stan t (Table V). Th ese con stan ts are lowest in m eth an ol, wh ich corre-
spon ds with th e fact th at m eth an ol solvates well th e an ion form ed in th e
dissociation , an d th us decreases th e n eed for stabilisation of th e an ion by
dispersin g th e ch arge over th e m olecule; such dispersin g process is con sid-
erably affected by electron ic effects of substituen ts. Th e reaction con stan t
ρXp can be com pared with th e reaction con stan t ρ1, wh ich quan tifies th e
substituen t effect on th e dissociation con stan t value of meta an d para sub-
stituted ben zen esulfon am ides11–13 , wh ile th e reaction con stan t ρYp can be
com pared with ρ2 foun d for th e dissociation processes of N-ph en ylben zen e-
sulfon am ides substituted in meta an d para position s of th e an ilin e rin g19.
Th e values of th ese reaction con stan ts are sum m arised in Table V givin g
also th e reaction con stan t ratios ρYp /ρpX an d ρoY /ρXo , wh ich express h ow m an y
tim es th e dissociation is m ore sen sitive to electron ic effects of Y substitu-
en ts th ose of X substituen ts. Th e ρ1 value foun d in m eth an ol is question -
able because it is low com pared with th e oth er ρ1 con stan ts; n eglectin g it,
we can claim th at th e correspon din g con stan ts are m ore or less iden tical.
We can see th at th e ρYo /ρoX ratio for in dividual solven ts is som ewh at h igh er
th an th e ρYp /ρXp ratio, an d th e order of solven ts arran ged accordin g to m ag-
n itude of th ese ratios rem ain s th e sam e.
TABLE V
Com parison of th e reaction con stan ts ρXp an d ρpY with th e reaction con stan ts ρ1, ρ2, ρXo , an d
ρYo . Th e ρ1 an d ρ2 con stan ts were obtain ed by regression of pKHA values versus substituen t
con stan ts σm an d σp for meta an d para substituted ben zen esulfon am ides (ρ1) an d meta an d
para substituted N-ph en ylben zen esulfon am ides (C6H5SO2NHC6H4-Y, con stan t ρ2)
Solven t
ρ1
ρpX
ρoX
ρ2
ρpY
ρoY
ρ1/ρ2
ρYp /ρXp
ρYo /ρXo
MeOH
DMSO
DMF
Py
–0.52
–1.91
–2.03
–2.06
–2.22
–2.10
–1.49
–2.00
–2.10
–2.19
–2.42
–2.15
–0.90
–1.23
–1.27
–1.30
–1.43
–1.27
–2.11
–3.28
–3.69
–
–2.27
–3.47
–3.60
–3.44
–3.58
–3.05
–1.44
4.05
1.52
1.60
–2.23
–2.29
–2.14
–2.22
–1.90
1.72
1.81
–
1.74
1.71
1.57
1.47
1.41
1.81
1.80
1.64
1.55
1.49
Me2CO
AN
–
–
–2.70
1.28
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Substituted N-Phenylbenzenesulfonamides
1389
Evaluation of Measured Data by Methods with Latent Variables
For th e purpose of an alysis of substituen t effects by th ese m eth ods, we com -
piled two m atrices (XY an d YX) out of th e average pKHA values. Both of
th em were th en stan dardised an d subjected to calculation by prin cipal
com pon en t an alysis14 (PCA) an d con jugate deviation an alysis15 (CDA).
First, a square m atrix 5 × 5 was con structed for each solven t, th e rows
represen tin g th e pKHA values of sulfon am ide groups with con stan t X
substituen t an d colum n s represen tin g th ose of sulfon am ides with con stan t
Y substituen t. Th ese square m atrices were arran ged side-by-side, wh ich re-
sulted in a fin al XY m atrix of 5 rows an d 30 colum n s. Th e YX m atrix was
con structed by orderin g th e tran sposed m atrices side-by-side. Both resultin g
m atrices were 100% full.
Th e statistical ch aracteristics sh ow th at th e variability of both source m a-
trices can be sufficien tly described by two laten t variables. In both types of
calculation , th e first laten t variable explain s 97.45 an d 98.42% of variabil-
ity of data in th e XY an d YX m atrices, respectively. Th e variability ex-
plain ed by th e secon d laten t variable is sligh tly differen t in th e two types of
calculation . Th e PCA m eth od gives 2.13 an d 1.29% for XY an d YX m atrices,
respectively, th e CDA m eth od gives 1.19 an d 1.00% for XY an d YX m atri-
ces, respectively. For both source m atrices, it h olds true th at th e values of
th e vector of th e first laten t variable decrease from m eth oxy group to n itro
group (Table VI), th e order approxim ately correspon din g to th e polar ef-
fects of th e substituen ts. Hen ce it can be presum ed th at th e first laten t vari-
TABLE VI
Vectors of laten t variables isolated from PCA an d CDA calculation s on XY an d YX m atrices
XY–PCA
XY–CDA
YX–PCA
YX–CDA
X an d Y
t1
t2
t1
t2
t1
t2
t1
t2
H
0.562
0.529
1.000
0.394
0.000
0.859
1.000
0.000
0.579
0.056
0.559
0.526
1.000
0.393
0.000
0.858
1.000
0.000
0.581
0.056
0.769
0.759
1.000
0.391
0.000
0.000
0.052
1.000
0.379
0.603
0.791
0.780
1.000
0.400
0.000
0.000
0.049
1.000
0.377
0.602
CH3
OCH3
Cl
NO2
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1390
Nádvorník, Ludwig:
able describes just th ese properties of substituen ts. In order to support th is
presum ption , we carried out lin ear regression of th e vector of th e first la-
ten t variable obtain ed by th e PCA an d CDA calculation s versus all th e types
of th e above-discussed substituen t con stan ts describin g electron ic effects of
substituen ts. Th e results are sim ilar for th e laten t variables obtain ed from
both types of calculation ; th erefore, we will presen t h ere on ly th e results for
th e laten t variables obtain ed by PCA calculation . It was foun d th at th e vec-
tor of th e first laten t variable of both th e XY an d YX m atrices correlates
best with th e σp con stan ts (XY: s = 0.151, R = 0.931; YX: s = 0.090, R =
0.979), wh ich is in accordan ce with th e above-m en tion ed fin din g: th e lin -
ear regression of pKHA values versus th ose substituen t con stan ts th at are
supposed to reflect on ly th e electron ic substituen t effects gives th e best re-
sults just for th e σp con stan ts. However, th e calculated statistical ch aracter-
istics sh ow th at th e depen den ces obtain ed are n ot very close, wh ich is
particularly true for th e vector of th e first laten t variable of th e XY m atrix.
At first sigh t, we can n otice, e.g., th at th e value for m eth yl group in th e vec-
tor of th e first laten t variable of both source m atrices is lower th an th at ex-
pected for th e variable reflectin g solely th e electron ic substituen t effects.
Th is can be explain ed by poten tial operation of th e steric effect in th e for-
m ation of th is laten t variable. From th is poin t of view, it is in terestin g th at
th e t1 vector of th e YX m atrix (i.e., th e Y substituen ts) correlates with th e σp
substituen t con stan ts better th an th e t1 vector of th e XY m atrix (X substitu-
0.60
p
2
0.40
0.20
0.00
–0.20
–0.40
2.60
2.65
2.70
2.75
p
1
FIG. 1
Position of poin ts in th e space of loads from th e PCA calculation for th e XY source m atrix:
❍ m eth an ol, ❍ dim eth yl sulfoxide, ∆ dim eth ylform am ide, ❍ pyridin e, ❍ aceton e, ❍
aceton itrile
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Substituted N-Phenylbenzenesulfonamides
1391
en ts) does. In th is case, quite th e opposite could h ave been an ticipated
sin ce th e Y substituen ts are closer to th e reaction cen tre, an d th eir steric ef-
fects sh ould th us be stron ger. Th is fact could be explain ed by deviation of
th e rin g plan e m akin g th e substituen t m ore distan t from th e reaction cen -
tre an d th e steric effect lower. Th e deviation would also weaken th e direct
con jugation with th e reaction cen tre an d th us im prove th e correlation with
th e σp substituen t con stan ts.
For a better un derstan din g of th e in fluen ces operatin g in th e creation of
th e secon d laten t variable, wh ich is statistically sign ifican t with both th e
source m atrices, it is h elpful to con struct th e space of loads in wh ich each
colum n of th e source m atrix is ch aracterised by on e poin t. Figures 1 an d 2
sh ow th at th e poin ts are dislocated in th e space of loads in such a way as to
form two bran ch es. It is th e sign of th e p2 value wh ich determ in es to wh ich
bran ch a poin t will belon g. If th e poin ts in th e figures are den oted with in -
dividual solven ts, it can be seen th at in both figures on e bran ch is form ed
by th e MeOH, DMSO, an d DMF solven ts an d th e oth er by Py, Me2CO, an d
AN. Th e properties of substituen ts probably determ in e th e beh aviour of sol-
ven ts in th e dissociation an d th eir division in to two groups accordin g to
th e sim ilarity of th is beh aviour. Th is can be presum ed on th e basis of th e
fact th at th e location of a poin t in th e space of loads depen ds n ot on ly on
th e solven t but also on substitution . Th is substituen t–solven t in tercon n ec-
tion is apparen tly reflected in th e secon d laten t variable.
0.40
p
2
0.20
0.00
–0.20
–0.40
2.48
2.50
2.52
2.54
p
1
FIG. 2
Position of poin ts in th e space of loads from th e PCA calculation for th e YX source m atrix;
for sym bols see Fig. 1
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

1392
Nádvorník, Ludwig:
The authors are indebted to the Ministry of Education, Youth and Sports of the Czech Republic for
financial support (Research project CIMSM 253 100001).
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Collect. Czech. Chem. Commun. (Vol. 66) (2001)