Dissociation of amides in strongly basic medium of sodium methoxide in dimethyl sulfoxide-methanol mixtures

Article abstract of DOI:10.1135/cccc19971562

The dissociation constants of eleven amides have been measured in methanol and its mixtures with dimethyl sulfoxide (10 to 80% v/v) using sodium methoxide as the base. The experimental dissociation constants have been used to construct the H_- acidity function as a function of methoxide concentration and composition of the DMSO-MeOH mixture as well as function of methoxide concentration in methanol. Moreover, with the help of construction of acidity function, the functions have been devised for constant sodium methoxide concentrations (0.025, 0.1, and 0.2 mol 1^-1) and changing composition of the DMSO-MeOH mixture.

Full text of DOI:10.1135/cccc19971562

1
562
Mitas, Kavalek, Pytela:
DISSOCIATION OF AMIDES IN STRONGLY BASIC MEDIUM OF SODIUM
METHOXIDE IN DIMETHYL SULFOXIDE–METHANOL MIXTURES
1
2
3
Petr MITAS , Jaromir KAVALEK and Oldrich PYTELA
Department of Organic Chemistry, University of Pardubice, 532 10 Pardubice, Czech Republic;
1
2
3
e-mail: mitas@hlb.upce.cz, kavalek@hlb.upce.cz, pytela@hlb.upce.cz
Received April 3, 1997
Accepted May 9, 1997
The dissociation constants of eleven amides have been measured in methanol and its mixtures with
dimethyl sulfoxide (10 to 80% v/v) using sodium methoxide as the base. The experimental dissoci-
ation constants have been used to construct the H– acidity function as a function of methoxide con-
centration and composition of the DMSO–MeOH mixture as well as function of methoxide
concentration in methanol. Moreover, with the help of construction of acidity function, the functions
–
1
have been devised for constant sodium methoxide concentrations (0.025, 0.1, and 0.2 mol l ) and
changing composition of the DMSO–MeOH mixture.
Key words: Acidity functions; Dissociation constants of amides.
The sodium methoxide catalyzed cyclization of N-substituted α-aminoamides 1a–1d
represents one of alternative syntheses of substituted imidazolinones, one of the new
1
promising classes of herbicides . Other conceivable synthetic routes to these com-
2
pounds involve reactions of imidoesters with esters of amino acids , oxidations of imi-
3
4
dazoles with lead(IV) acetate , desulfurization of thiohydantoins with Raney nickel ,
5
and cyclizations of aminoamides in strongly basic media (barium hydroxide in methanol ,
6
6
sodium hydride in toluene , or sodium methoxide in methanol ). The quoted papers
dealing with the cyclization reactions of aminoamides are predominantly focused on
synthetic aspects. The authors did not pay attention to systematic kinetic studies,
measurements of dissociation constants of the N-substituted α-aminoamides, and a
choice of suitable solvent systems.
On the basis of the papers mentioned we can suggest a reaction mechanism for the
cyclization reactions of N-substituted α-aminoamides catalyzed with sodium methoxide
(
Scheme 1). The cyclization itself is probably initiated by a rapid pre-equilibrium of
deprotonation of the substrate at one of its acidic centres, only anion 3 formed by
deprotonation at the acetamide centre being able to undergo the next cyclization steps.
Any detailed kinetic study of the given cyclization reaction needs the knowledge of
actual concentration of anion 3, which can be determined from the dissociation con-
stants and acidity functions. Suitable media involve protic solvents or their mixtures
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1563
with polar aprotic solvents, which readily dissolve the reactants and do not much sol-
vate the base used.
The acid-base properties of weak acids in protic and aprotic solvents in the presence
of sodium methoxide as the base have already been dealt with by some authors using
7
various series of substituted C-, N-, and O-acids. For instance, Schall and Lambert as
8
well as More O’Ferrall and Ridd used series of substituted anilines and dipheny-
–
lamines as the indicators for the MeO /MeOH system. The H and H scales obtained
–
m
by them, of course, depend on the type of the indicator used: the two scales are practi-
9
cally identical for the same value of autoprotolytic constant of methanol. Kaválek
constructed an acidity function in the same medium, using a series of substituted for-
1
0
manilides. Rochester describes the same medium by several scales using several
series of substituted phenols. His acidity scales for O-acids differ slightly from one
another, but they show a considerable deviation from the H and H scales found with
m
–
the help of series of substituted N-acids.
Bowden and Stewart and Kroeger and Stewart12 constructed a H scale with series
11
–
of C-acids (substituted α-cyanostilbenes) for the binary solvent system dimethyl
sulfoxide–methanol (DMSO–MeOH), which represents a transition between a protic
and an aprotic solvent. This solvent system also seems to be the most suitable for
syntheses of imidazolinone derivatives as well as for mechanistic studies of the cycli-
zation reaction of N-substituted α-aminoamides. There is no available paper dealing
with the acid-base properties of N-substituted α-aminoamides 1a, 1b, 1d, 1e, and 1k in
the DMSO–MeOH medium with sodium methoxide as the base.
2
R
1
R
R
CO
N
CCONH
2
2
KA
’
3
R
R
1
R
CONHCCONH
+ CH O
3
2
2
a-2d
3
+
CH3OH
R
2
K
R
A
1a-1d
1
CONHCCONH
3
R
3a-3d
k
2
R
N
N
1
3
R
R
O
H
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
564
Mitas, Kavalek, Pytela:
The papers quoted present the acidity functions constructed with the help of sub-
stituted anilines and phenols for various concentrations of sodium methoxide and con-
stant composition of the solvent mixture, or for one concentration of sodium methoxide
and changing composition of the mixed solvent. (The effect of both factors, i.e. the
base concentration and solvent composition, has not been studied, nor have been con-
structed acidity functions for individual DMSO–MeOH mixtures.)
The aim of the present communication, therefore, is a study of the acid-base proper-
ties of N-substituted α-aminoamides in DMSO–MeOH mixtures with sodium methox-
ide as the base. For the purpose of construction of acidity function the series of
N-substituted α-aminoamides has been extended by substituted acetanilides and for-
manilides, which has made it possible to cover the whole concentration range of so-
dium methoxide in the DMSO–MeOH mixture.
THEORETICAL
The deprotonation of acid HA in solutions of sodium methoxide in DMSO–MeOH
according to Eq. (1) can be described by the thermodynamic equilibrium constant KA
expressed by Eq. (2).
HA + MeO–
A + MeOH
–
(1)
(2)
–
–
K = ([A ]a
/[MeO ][HA])(γ
A
−
/γMeO γHA)
−
A
MeOH
The standard modification of Eq. (2) gives Eq. (3) wherefrom the acidity function H–
can be defined as in Eq. (4).
–
pK = log I + log [MeO ] + log (γ
−
γHA/γA
−
) – log aMeOH
(3)
(4)
A
MeO
–
H = log [MeO ] + log (γ
−
γHA/γA ) – log aMeOH
−
–
MeO
In Eq. (2) the activities are defined by a product of concentration and activity coeffi-
cient. With changing sodium methoxide concentration or changing methanol content in
its mixture with dimethyl sulfoxide the activity coefficients need not necessarily remain
equal to one. That is why we must know their changes affected by the two factors.
The dissociation constants of indicators can be calculated from Eq. (3) on the condi-
tion that the activity coefficients are equal to one. If not, then the dissociation constants
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1565
–
can be obtained from the linear dependence log Q = log I + log [MeO ] vs c
−
as the
MeO
8
intercept at ordinate axis . The obtained value of log Q is an extrapolation to the infi-
0
nitely diluted solution of methoxide.
An alternative possibility of evaluation of dissociation constants is based on the ap-
1
3
plication of the general acidity function published in the form of Eq. (5) for methan-
olic solutions of sodium methoxide,
–
log I + log [MeO ] = pK + m* X ,
(5)
A
where X is a function of analytical concentration of sodium methoxide describing the
nonideality of medium, and m* is a sensitivity coefficient.
EXPERIMENTAL
Syntheses of the Substances Studied
The indicators 2-(4-nitrobenzoylamino)-2,3-dimethylbutanamide (1a), 2-(4-nitrobenzoylamino)-2-
phenylpropanamide (1b), 2-(4-nitrobenzoylamino)-2(4-nitrophenyl)propanamide (1c), 2-(4-nitro-
benzoylamino)-2,3-dimethylbutanenitrile (1d), and 4-nitrobenzoylglycinamide (1e) were prepared by
1
4
known methods . The acetanilides 4-nitroacetanilide (1f) and 3-nitroacetanilide (1g) were prepared
by acetylating the respective amines with acetic anhydride; the formanilides 4-nitroformanilide (1h),
3
-nitroformanilide (1i), and 4-bromoformanilide (1j) were prepared by formylating the respective
1
5
amines with 98% formic acid .
Synthesis of N-(4-Nitrobenzoylaminoethanoyl)pyrrolidine (1k)
Glycine (20 g, 0.26 mol) was dissolved in methanol (150 ml), the cold solution was saturated with
hydrogen chloride (37 g, 1 mol), and then refluxed 4 h. After distilling off the methanol, quantitative
1
6
yield (33.7 g) of methyl glycinate hydrochloride was isolated; m.p. 172–175 °C (ref. gives m.p.
1
72–174 °C).
Methyl glycinate hydrochloride (2 g, 0.016 mol) was mixed with chloroform (35 ml) and triethyl-
amine (4.45 ml, 0.032 mol) and treated with 4-nitrobenzoyl chloride (2.97 g, 0.016 mol) in chloro-
form (10 ml). The temperature of reaction mixture increased to 50 °C, and after standing for 24 h a
homogeneous solution was formed which was evaporated until dry. The yellowish crystals were
washed with water (2 × 5 ml) and recrystallized from distilled water to give 2.46 g (65%) methyl
1
7
4
-nitrobenzoylglycinate, m.p. 150–152 °C (ref. gives m.p. 151–152 °C). For C H N O (238.2)
10 10 2 5
calculated: 50.42% C, 4.23% H, 11.76% N; found: 50.31% C, 4.21% H, 11.59% N.
A suspension of methyl 4-nitrobenzoylglycinate (1 g, 4.2 mmol) in pyrrolidine (7.1 g, 8.33 ml, 0.1 mol)
was refluxed until a dark yellow homogeneous solution was formed (6 h). Then the excess pyrrolidine
was distilled off in vacuum, and the distillation residue was recrystallized from a chloroform–cyclo-
1
8
hexane mixture (1 : 1). The acylated pyrrolidine 1k (0.61 g, 52%) melted at 174–178 °C (ref. gives
m.p. 174–177 °C). For C13H15N O (277.3) calculated: 56.31% C, 5.45% H, 15.15% N; found:
3
4
1
5
6.07% C, 5.44% H, 15.10% N. The identity of product was verified by the H NMR spectrum
(AMX 360 Bruker spectrometer; 360.14 MHz; 25 °C). The chemical shifts are referenced to the solvent
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
566
Mitas, Kavalek, Pytela:
signal (δ( H) 7.25): 8.25 and 7.79 AA′XX′, 2 × 2 H (arom.); 7.52 brs, 1 H (NH); 4.15 d, 3J = 4.03
1
(
NHCH ); 3.52 t and 3.43 t, 2 × 2 H (2 × NCH ); 2.02 m and 1.90 m, 2 × 2 H (2 × CH ).
2
2
2
Solvents
Methanol p.a. (Aldrich) was distilled under argon and kept in a bottle with molecular sieve A4. Dimethyl
sulfoxide p.a. (Aldrich) was kept in a bottle with molecular sieve A4. The water content (according
–
1
to Fischer) was 0.09–0.12% w/w. Sodium methoxide was prepared as a 5 mol l solution by dissolving
sodium metal in methanol rid of carbon dioxide by distillation under argon. Solutions of required
concentrations were obtained by diluting this stock solution with methanol, and the sodium methoxide
content was determined by titration with standard hydrochloric acid solution.
Measurements of Dissociation Constants
The dissociation constants of indicators 1a–1k were measured spectrophotometrically in DMSO–MeOH
mixtures, containing from 0 to 80% v/v dimethyl sulfoxide, at 25 °C using the diode array appara-
tuses Hewlett-Packard 8452 and 8453. A 1 cm quartz cell with a lid was charged with 2 ml respec-
tive sodium methoxide solution and placed in the thermostated cell compartment of the
–
2
–1
spectrophotometer. Then 20 µl methanolic solution of substrate (c 1 . 10 mol l ) was injected and
after mixing the spectrum was measured to 5 s in the wavelength range from 200 to 500 nm.
RESULTS AND DISCUSSION
The indicators 1a–1k used in the construction of the acidity function gave spectral
records with sharp and well-developed isosbestic points. The spectrum of the conjugate
base of N-substituted α-aminoamide 1e exhibited a second isosbestic point due to the
change of methoxide concentration, which we interpret by simultaneous dissociation at
the benzamide and acetamide centres (Scheme 1). Therefore, the analytical wavelength
was chosen just at this newly formed isosbestic point to ensure a constant value of
absorbance for the conjugate base. Acetamide is a ca two orders weaker N-acid than
1
9
benzamide (pK ’s of benzamide and acetamide in DMSO are 23.35 and 25.5, respec-
A
tively), hence in a molecule of N-substituted α-aminoamides 1a, 1b, 1d, and 1e the
dissociation will preferably take place at the benzamide centre unless the α-carbon in
the acetamide moiety is substituted (R2,3 = H). If it is substituted, then the dissociation
at this centre is sterically hindered (R ≠ H), and the acetamide centre is also partially
2
,3
2
0
deprotonated . This conclusion is also supported by the UV-VIS spectra of N-sub-
stituted α-aminoamides 1a, 1b, and 1d which show no second isosbestic points in the
case of disubstitution (R2,3 ≠ H). For verification of this conclusion we measured, too,
the spectra of 4-nitrobenzoylglycinamide (1e) where it is also possible to deprotonate
two centres and no steric hindrance is present. The UV-VIS spectra measured revealed
that the dissociation took place at the benzamide centre, but in the most concentrated
solutions of sodium methoxide the acetamide centre was simultaneously deprotonated,
which was manifested by appearance of a new isosbestic point. Another interpretation
of the new isosbestic point can lie in the change of optical density when the spectra of
the conjugate base are measured, especially so if a nitro group is present as the 4-sub-
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1567
stituent, which results in considerable delocalization of negative charge of the conju-
gate base, or in a specific effect of mixed solvent on the deprotonation of substrate
which is noticeable just in the methoxide solutions of the highest concentrations.
Also when measuring the spectra of conjugate bases of some acetanilides and for-
manilides, we have observed shifts in the existing isosbestic points and formation of
new ones. In particular, such changes were observed with the indicators 1f–1i in neat
methanol and in its mixtures with 10 and 20% v/v DMSO. These spectra were statisti-
2
1
cally analyzed with the help of the method of principal components . The absorbance
values were arranged into a source matrix whose columns and rows corresponded to
selected wavelengths and to the individual methoxide concentrations, respectively. By
decomposition of this matrix we obtained the first principal component with the help of
which it is possible (in the so-called short cycle) to reconstruct the original matrix
without disturbing effects. For instance, the application of this procedure to the spectral
record of indicator 1f in 20% v/v DMSO (Fig. 1) gave the result depicted in Fig. 2.
The values of analytical wavelengths and ∆pK (read from the dependence of log I
A
vs log cMeO
are given in Table I, and the limit values of log I vs cMeO
treated in two ways: with the help of general acidity function and by constructing the
−
or log Q vs cMeO
−
and referenced to the standard indicator 1h in methanol)
−
in Table II. The results were
1
3
2
2
acidity function with the help of the recently suggested algorithm .
Calculation of ∆pKA of Studied Indicators in Methanol Using General Acidity
1
3
Function
The differences of dissociation constants of the indicators 1c, 1d, and 1g–1j in methanol
were calculated by means of the general acidity function. The sensitivity coefficients
m* were calculated from the dependences of log Q vs log Q, where log Q and log Q
st
st
are the values for the standard indicator 1h and those for the given indicator, respec-
1
A
1
.50
.25
.00
1
0
.75
.50
0
0
.25
.00
0
FIG. 1
Electronic spectra of 4-nitroacetanilide measured
in 20% v/v DMSO
240
290
340
390
440
λ, nm
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
568
Mitas, Kavalek, Pytela:
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1569
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
570
Mitas, Kavalek, Pytela:
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
TABLE II
1571
Values of limit ionization ratios log I vs cMeO− of indicators 1a–1k in MeOH with 0–80% v/v DMSO
log I
max min
cMeO−, mol l–1
log I
max min
cMeO−, mol l–1
max min
Indi- DMSO
cator % v/v
Indi- DMSO
cator % v/v
max
min
1
c
0
0
0.70 –1.00
0.65 –0.40
0.38 –0.93
1.08 –0.79
1.02 –0.50
1.02 –0.79
0.72 –1.03
0.77 –1.00
0.73 –1.07
0.90 –0.70
0.69 –0.88
0.41 –1.08
0.90 –0.89
0.80 –0.97
1.00 –0.57
0.95 –0.96
0.89 –0.98
0.42 –0.98
0.45 –0.93
0.92 –0.86
0.91 –0.57
0.58 –1.03
0.72 –0.74
0.95 –0.81
0.65 –0.97
0.66 –0.95
0.83 –0.91
1.15 –0.35
1.80
0.80
2.00
3.50
0.50
0.80
2.00
1.00
0.50
0.50
0.80
0.25
1.00
1.40
0.25
0.60
1.60
0.40
0.20
0.10
0.50
1.00
0.40
0.20
1.40
0.50
2.00
0.10
0.10
0.10
0.25
0.60
0.025
0.025
0.10
0.05
0.02
0.02
0.05
0.01
0.07
0.10
0.007
0.007
0.05
0.02
0.01
0.003
0.01
0.10
0.02
0.005
0.10
0.02
0.07
0.003
1i
1j
40
40
50
50
50
50
50
50
60
60
60
60
60
60
60
60
70
70
70
70
70
70
80
80
80
80
80
80
0.83 –0.76
0.71 –0.83
0.42 –1.05
0.88 –0.74
0.71 –0.73
0.52 –0.63
0.91 –0.98
0.73 –0.87
0.57 –1.08
0.74 –0.42
0.70 –0.78
0.57 –1.07
0.39 –1.07
0.74 –0.79
1.06 –0.48
0.81 –0.80
0.68 –0.74
0.97 –0.56
0.96 –0.90
1.05 –0.80
1.05 –1.00
1.01 –0.98
0.48 –0.67
1.07 –0.47
0.68 –1.06
1.31 –0.01
1.00 –0.63
0.67 –0.92
0.10 0.003
0.60 0.03
1.20 0.30
0.70 0.08
0.20 0.008
0.04 0.003
1.00 0.04
1.00 0.15
1.00 0.15
0.05 0.005
0.025 0.001
0.30 0.01
0.05 0.002
0.20 0.01
0.025 0.001
0.70 0.10
0.20 0.01
0.025 0.001
0.20 0.005
0.05 0.001
0.10 0.001
0.50 0.025
0.20 0.025
0.10 0.005
0.025 0.001
0.01 0.001
0.05 0.001
0.20 0.01
1
d
1
f
0
1a
1b
1c
1d
1e
1k
1a
1c
1d
1e
1f
1
1
g
0
h
0
1
i
0
1
j
0
1
c
10
10
10
20
20
20
20
20
20
20
30
30
30
30
40
40
40
40
40
40
40
1
d
1
i
1
c
1
d
1
f
1
1
g
1g
1i
h
1
i
1k
1b
1c
1e
1f
1
j
1
c
1
1
d
h
1
i
1g
1k
1a
1b
1e
1f
1
b
1
c
1
d
1
e
1
f
1
1
g
1g
1k
h
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
572
Mitas, Kavalek, Pytela:
tively. The individual differences of dissociation constants were then calculated from
Eq. (5) (Table I).
The calculated ∆pK values do not show any significant deviations from those ob-
A
tained from the dependence of log I vs log cMeO
−
or log Q vs cMeO
−
(Table I) or the
values of dissociation constants calculated by means of iterative construction of acidity
function (Table I) even in spite of the fact that the requirement of constant ratio of
activity coefficients of indicators and their respective conjugated bases was not ful-
filled. From among the indicators measured, the acid-base properties of 1f considerably
deviated and this indicator was replaced by 1i whose acid-base properties were the
closest to the indicator series measured. The nonhomogeneity of ratios of activity coef-
ficients of the series measured is predominantly caused by the application of several
different structures of indicators, which made itself felt distinctly in the individual sen-
sitivity coefficients m*, as it can be seen in Table I. The structural variety, which is a
considerable complication in constructing acidity functions, could not be avoided due
to the absence of suitable indicators. It can be stated that the application of the con-
structed general acidity function to this series of N-acids leads (in spite of the above-
mentioned structural problem) to dissociation constants which agree well with the
results obtained in the classic way or by the new iterative procedure of construction of
acidity function.
Calculation of Dissociation Constants through Construction of Acidity Function
The acidity function H and the ∆pK values in individual DMSO–MeOH mixtures
–
A
2
2
were calculated by means of the algorithm devised by Pytela . 4-Nitroformanilide (1h)
was used as the standard indicator, and to this value were referred the ∆pK ’s of the
A
other indicators measured (Table I) and the calculated acidity functions in methanol
1
.55
A
1
0
0
.15
.75
.35
FIG. 2
–
0.05
2
Electronic spectra calculated by means of factor
440 analysis from original data
40
290
340
390
λ, nm
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1573
and its mixtures with dimethyl sulfoxide (Table III) and H at constant concentrations
–
of base and varying composition of the solvent mixture (Table III). In the way de-
scribed we calculated, from the log I values measured, the ∆pK of indicators and their
A
standard deviations and then the slope values of the dependence of log I vs H . One
–
third of these calculated slope values exhibit statistically significant deviations from
unit slope (from 0.786 to 1.593), which is especially the case with substituted aceta-
nilides and formanilides 1f–1j whose ratios of activity coefficients of indicator and its
respective conjugate base are different from those of N-substituted α-aminoamides 1a,
1
b, 1d, 1e, and 1k. This deviation from unit slope is also observed with the indicator 1e
whose most concentrated solutions presented the above-mentioned problems potentially
introducing error into the determination of log I. The ∆pK values calculated by this
A
method (Table I) stand in very good accordance with the experimentally determined
1.0
H
A
2,3,4
0.8
1
FIG. 3
0.6
The acidity function constructed with the help of
2
2
algorithm for changing concentration of sodium
1
0.4
methoxide in methanol 2, compared with published
acidity functions for this medium 3 (ref. ), 4
ref. ). The acidity function (curve 1) constructed 0.2
9
2,3,4
8
(
with the help of the same algorithm for changing
sodium methoxide concentration in DMSO–
MeOH mixture. The acidity functions H– were
standardized in the interval 〈0,1〉
0.0
0
.2
0.7
1.2
1.7
2.2
[
2.7
–
MeO ]
1
.0
H
–
0
.8
.6
0
2
FIG. 4
4
2
3
0.4
Comparison of published acidity function (curve
) with the acidity function constructed by means
of algorithm for constant sodium methoxide con-
3
1
1
2
2
0
.2
–
1
–1
centrations (0.025 mol l (2), 0.1 mol l (3), 0.2
–
1
mol l (4)) and varying composition of DMSO–
MeOH mixture. The acidity functions H– were 0.0
standardized in the interval 〈0,1〉
0
20
40
60
80
X
DMSO
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
574
Mitas, Kavalek, Pytela:
∆
pK values (Table I) as well as with those calculated by means of the general acidity
A
function in methanol (Table I). The H acidity function has been constructed as a func-
–
tion of both variables, i.e. sodium methoxide concentration and solvent mixture compo-
sition, as well as a function of sodium methoxide concentration in methanol (Table III).
For the individual DMSO–MeOH mixtures (from 10 to 80% v/v) we have constructed,
using the algorithm, the acidity functions like those in methanol for changing base
concentration, because standard indicators in the individual mixtures are not known.
From among the series of indicators measured in the individual mixtures none could be
considered standard since the calculated acidity functions in the individual mixtures
cannot be mutually compared due to the fact that differences between the individual
media measured are not known. The last type of the acidity functions constructed are
–
1
those for constant methoxide concentrations (0.025, 0.1, 0.2 mol l ) and varying com-
position of DMSO–MeOH mixtures (Table III).
Analysis of Constructed and Published Acidity Functions in DMSO–MeOH
Mixtures with Sodium Methoxide as Base
The acidity function constructed as a function of both variables, i.e. methoxide and
DMSO concentration changes (Fig. 3, curve 1), could not be compared with any similar
published function, since no such function has been constructed yet. The acidity func-
tion devised as a dependence of methoxide concentration in methanol was compared
8
,9
with the functions published . All the analyzed functions were standardized in the
interval 〈0,1〉 (see Fig. 3, curves 2, 3, 4), and it can be seen that the acidity function
constructed by us is practically identical with those published. Another type of acidity
functions constructed by us are those for varying composition of DMSO–MeOH mix-
ture with constant concentration of the base. The acidity function of this type was only
2
3
–1
published for the sodium methoxide concentration of 0.025 mol l : it was stand-
ardized in the interval of 〈0,1〉 and compared with the acidity functions constructed by
–
1
us for the sodium methoxide concentrations of 0.025, 0.1, and 0.2 mol l . The con-
structed acidity functions differ from that published in the whole range (Fig. 4). The
increasing concentration of polar aprotic DMSO affects the activity coefficients of the
indicators used (amides vs amines) and their respective conjugated bases in different
ways, which can be one of the reasons of differences between the functions compared.
The experimental and calculated ∆pK values of indicators 1h–1j in methanol were
A
9
compared with the published values and found identical with them within experimental
error of determination of dissociation constants.
By constructing these acidity functions we managed to describe the DMSO–MeOH
medium studied in the way sufficient for determination of actual concentration of the
reactive anion (Scheme 1) formed in the pre-equilibrium of the cyclization reaction,
and from this concentration to determine the real reaction rate of the cyclization reac-
tion necessary for a detailed description of the reaction.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Dissociation of Amides
1575
TABLE III
The H– function calculated by means of construction of acidity function
–
[
MeO ]
a
b
DMSO
% v/v
c
d
e
–
1
H–
H–
H–
H–
H–
mol l
3
3
2
2
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.5
.0
.5
.0
.8
.6
.4
.3
.2
.0
.8
.7
.6
.5
.4
.3
3.159
2.681
2.283
2.029
1.924
1.845
1.760
1.712
1.692
1.575
1.437
1.350
1.181
1.038
0.893
0.718
0.605
0.507
0.338
0.162
0.078
–0.008
–0.164
–0.252
–0.386
–0.460
3.040
2.569
2.241
1.936
1.820
1.726
1.636
1.581
1.528
1.415
1.314
1.209
1.095
0.985
0.867
0.705
0.626
0.529
0.316
0.196
0
10
20
30
40
50
60
70
80
–1.563
–1.313
–1.078
–0.829
–0.594
–0.205
0.359
–1.605
–1.409
–1.193
–0.952
–0.765
–0.557
–0.042
0.383
–2.525
–2.295
–2.126
–1.886
–1.561
–1.241
–0.814
–0.239
0.395
0.778
1.739
0.529
.25
.2
.15
.1
.08
.07
.05
.04
.03
.025
0.048
–0.132
–0.365
–0.454
a
b
For increasing concentrations of sodium methoxide and dimethyl sulfoxide; for increasing concen-
c
tration of sodium methoxide in neat methanol; for constant concentration of sodium methoxide
–
1
d
(
0.025 mol l ) and increasing concentration of dimethyl sulfoxide; for constant concentration of
–
1
e
sodium methoxide (0.1 mol l ) and increasing concentration of dimethyl sulfoxide; for constant
concentration of sodium methoxide (0.2 mol l ) and increasing concentration of dimethyl sulfoxide.
–
1
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1
576
Mitas, Kavalek, Pytela:
The research work was financially supported by the Grant Agency of the Czech Republic, Grant No.
2
03/94/0123.
REFERENCES
1. Sedlak M., Halama A., Kavalek J., Machacek V., Mitas P., Sterba V.: Collect. Czech. Chem.
Commun. 61, 910 (1996).
2
3
4
5
6
7
8
9
. Kjaer A.: Acta Chem. Scand. 7, 889 (1962).
. Rio G., Masure M. M.: Bull. Soc. Chim. Fr. 1972, 3882.
. Edward J. T., Lantos I.: Can. J. Chem. 45, 1925 (1967).
. Holladay M. W., Nadzan A. M.: J. Org. Chem. 56, 3900 (1991).
. Wepplo P.: Pestic. Sci. 39, 293 (1990).
. Schall R., Lambert G.: J. Chim. Phys. 1962, 1164.
. More O’Ferrall R. A., Ridd J. H.: J. Chem. Soc. 1963, 5030.
. Kavalek J., Krampera F., Sterba V.: Collect. Czech. Chem. Commun. 41, 1685 (1976).
1
1
1
1
1
0. Rochester C. H.: Q. Rev., Chem. Soc. 1966, 511.
1. Bowden K., Stewart R.: Tetrahedron 21, 261 (1965).
2. Kroeger D. J., Stewart R.: Can. J. Chem. 45, 2163 (1967).
3. Bagno A., Scorrano G., Terrier F.: J. Chem. Soc., Perkin Trans. 2 1990, 1017.
4. Sedlak M., Halama A., Kavalek J., Machacek V., Sterba V.: Collect. Czech. Chem. Commun. 60,
1
50 (1995).
1
1
1
5. Kavalek J., Sterba V.: Collect. Czech. Chem. Commun. 40, 1176 (1975).
6. Zidani A., Carrie R., Vaultier M.: Bull. Soc. Chim. Fr. EN 1, 71 (1992).
7. Williams A., Lucas E. C., Rimmer A. R., Hawkins H. C.: J. Chem. Soc., Perkin Trans. 2 1972,
6
27.
1
1
2
2
2
2
8. Fleury J. P., Clerin P.: Bull. Soc. Chim. Fr. 1973, 3134.
9. Bordwell F. G., Algrim D.: J. Org. Chem. 41, 2507 (1976).
0. Mitas P., Kavalek J., Sedlak M.: Collect. Czech. Chem. Commun., in press.
1. Simonds J. L.: J. Opt. Soc. Am. 53, 968 (1963).
2. Pytela O.: Collect. Czech. Chem. Commun. 62, 645 (1997).
3. Stewart R., O’Donnell J. P.: Tetrahedron 18, 917 (1962).
Collect. Czech. Chem. Commun. (Vol. 62) (1997)