The synthesis of sulfinylphthalimides and their reactions with some nucleophiles in dioxane

Article abstract of DOI:10.1080/10426507.2011.561457

In this study, some N-(p-substituted-arylsulfinyl)phthalimides (1a-1e) were synthesized. The synthesized compounds were examined with respect to their substitution reactions with sodium ethoxide, sodium methoxide, methylamine, and t-butylamine in dioxane.

Full text of DOI:10.1080/10426507.2011.561457

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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The Synthesis of Sulfinylphthalimides
and their Reactions with Some
Nucleophiles in Dioxane
Yasemin Soydas Bozkurt a & Halil Kutuk a
a Department of Chemistry, Faculty of Arts and Sciences, Ondokuz
Mayis University, Atakum, Samsun, Turkey
Version of record first published: 31 Oct 2011.
To cite this article: Yasemin Soydas Bozkurt & Halil Kutuk (2011): The Synthesis of
Sulfinylphthalimides and their Reactions with Some Nucleophiles in Dioxane, Phosphorus, Sulfur, and
Silicon and the Related Elements, 186:11, 2250-2257
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Phosphorus, Sulfur, and Silicon, 186:2250–2257, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.561457
THE SYNTHESIS OF SULFINYLPHTHALIMIDES
AND THEIR REACTIONS WITH SOME NUCLEOPHILES
IN DIOXANE
Yasemin Soydas Bozkurt and Halil Kutuk
Department of Chemistry, Faculty of Arts and Sciences, Ondokuz Mayis University,
Atakum, Samsun, Turkey
Abstract In this study, some N-(p-substituted-arylsulfinyl)phthalimides (1a–1e) were synthe-
sized. The synthesized compounds were examined with respect to their substitution reactions
with sodium ethoxide, sodium methoxide, methylamine, and t-butylamine in dioxane. The sub-
stituent effect was investigated at 30.0 0.1 ◦C. The activation entropy was also studied, and
negative ꢀS= values were obtained. Configuration inversions were observed in the substitution
reactions. This result is in conformity with the SN2 mechanism.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Characterization of -(p-Substituted-arylsulfinyl)phthalimides 1a–b.]
Keywords Arylsulfinylphthalimides; substituent effect; activation entropy; solvent effect; SN2
INTRODUCTION
Intheliterature, thefirstreportedsulfenimidewasN-(trichloromethylthio)phthalimide,
which was prepared by Kittleson1 by the reaction of trichloromethanesulfenylchloride
with sodium phthalimide. Alkyl and arylthioimides act as efficient sulfur transfer agents.2
Since the early 20th century, the chemistry of sulfinamides has been of continuing
interest3 because they are valuable precursors for the synthesis of chiral amines and their
derivatives, aziridines, sulfoximines, and related species, benzothiozines, olefins, and
ketones.4 Sulfinylphthalimides react rapidly with nucleophiles, resulting in displacement
of the phthalimide anion and formation of the corresponding sulfinyl derivative.5 Harpp
and Back attempted to synthesize N-(alkyl- and arylsulfinyl)phthalimides for possible
use as sulfinyl transfer reagents and reported that thiophthalimides conveniently oxidized
to the corresponding sulfinyl analogs in high yield by treatment with 1 equivelent of
m-chloroperbenzoic acid.6 Nucleophilic substitution at sulfur has been theoretically
studied by Bachrach.7 In a recent study, this reaction was explored for the particular case
of sulfinyl chlorides.8 Um et al. Reported, along with kinetic evidence for a stepwise
mechanism, the first spectroscopic observation of an intermediate in the reaction of a
sulfinate ester with NaOEt in anhydrous EtOH.9 A study of the kinetics and mechanism
Received 26 November 2010; accepted 31 January 2011.
We thank to the Ondokuz Mayis University (Grant No. F-336) for financial support of this work.
Address correspondence to Halil Kutuk, Department of Chemistry, Faculty of Arts and Sciences, Ondokuz
Mayis University, 55139 Atakum, Samsun, Turkey. E-mail: hkutuk@omu.edu.tr
2250

THE SYNTHESIS OF SULFINYLPHTHALIMIDES AND THEIR REACTIONS
2251
of the acid catalyzed hydrolysis of a series of N-(p-substitutedarylsulfinyl)phthalimides
have been studied in concentrated aqueous mineral acids in our laboratory.10 We now
report a complementary study of the nucleophilic substitution reactions of a series of
N-(p-substitutedarylsulfinyl)phthalimides (1a–e) in dioxane (Scheme 1).
Scheme 1
RESULTS AND DISCUSSION
In this study, N-(p-toluenesulfinyl)phthalimide (1a), N-(phenylsulfinyl)phthalimide
(1b), N-(p-chlorophenylsulfinyl)phthalimide(1c), N-(p-methoxyphenylsulfinyl)phthalimide
(1d), and N-(p-nitrophenylsulfinyl)phthalimide (1e) have been synthesized. The syn-
thesized compounds were examined with respect to their substitution reactions with
sodium ethoxide, sodium methoxide, methylamine, and t-butylamine in dioxane. In
order to determine the mechanism, substituent effect, solvent effect, activation entropy,
configuration change, and nucleophile effect were used as criteria.
The substituent effect was investigated at 30.0 0.1 ◦C in dioxane. Positive p val-
ues were obtained for the substitution of N-(p-substitutedarylsulfinyl)phthalimides with
sodium ethoxide, sodium methoxide, metylamine, and t-butylamine. Electron withdraw-
ing substituent (−Cl, −NO2) increases the reaction rate (Figure 1), while an electron
donating substituent (−CH3, −OCH3) leads to a decrease. A positive p value indicates
the SN2 mechanism or addition-elimination mechanism. The p values for the reaction
of N-(phenylsulfinyl)phthalimide in dioxane with sodium ethoxide, sodium methoxide,
methylamine, and t-butylamine were 0.83, 0.72, 0.68, and 1.51, respectively. Similar be-
havior has been observed for the alkaline hydrolysis of sulfonimidic esters.11 The kinetic
results are demonstrated graphically in Figures 1–4.
The activation entropy was also studied, and negative ꢀS= values were obtained. The
ꢀS= values for the reaction of N-(phenylsulfinyl)phthalimide in dioxane with sodium
methoxide, sodium ethoxide, methylamine, and t-butylamine were −79.53, −90.97,
−135.1, and −139.20 J/mol K, respectively. The negative ꢀS= values indicate that the
reaction followed the SN2 mechanism or addition-elimination mechanism. Similar be-
havior has been observed for the aminolysis of 1-tosyl-3-methyl imidazolium chloride.12
Arrhenius parameters for the reaction of N-(phenylsulfinyl)phthalimide in dioxane with
sodium ethoxide, sodium methoxide, methylamine, and t-butylamine are shown in Table 1.
Second order kinetics, showing dependence both on the nucleophile and on the
substrate, are widely observed in nucleophilic substitutions.13 It was also observed that the

2252
Y. S. BOZKURT AND H. KUTUK
Figure 1 Hammett plots for the reaction of N-(p-substitutedarylsulfinyl)phthalimide in dioxane with sodium
ethoxide.
reactions with sodium ethoxide and sodium methoxide nucleophiles took place much faster
than those with methylamine and t-butylamine nucleophiles as shown in Table 2.
Configuration inversion was observed in the substitution reaction of N-(p-
methoxyphenylsulfinyl)phthalimide with t-butylamine in dioxane. The rotation of the
plane of polarized light changed from +1.2◦ to −1.3◦. This result is in consisted with the
SN2 mechanism.
Figure 2 Hammett plots for the reaction of N-(p-substitutedarylsulfinyl)phthalimide in dioxane with sodium
methoxide.

THE SYNTHESIS OF SULFINYLPHTHALIMIDES AND THEIR REACTIONS
2253
Figure 3 Hammett plots for the reaction of N-(p-substitutedarylsulfinyl)phthalimide in dioxane with methy-
lamine.
In the light of the overall evidence, we propose that the substitution reactions of a
series of N-(p-substitutedarylsulfinyl)phthalimides with sodium ethoxide, sodium methox-
ide, methylamine, and t-butylamine occur with SN2 mechanism or addition-elimination
mechanism, as shown in Schemes 2 and 3 respectively.
Figure 4 Hammett plotsfor the reaction of N-(p-substitutedarylsulfinyl)phthalimide in dioxane with t-butylamine.

2254
Y. S. BOZKURT AND H. KUTUK
Scheme 2
EXPERIMENTAL
Materials and Methods
N-(p-Substituted-arylsulfinyl)phthalimides 1a–e were prepared from the correspond-
ing N-(p-substitutedarylthio)phthalimides with m-chloroperbenzoic acid in chloroform as
Scheme 3

THE SYNTHESIS OF SULFINYLPHTHALIMIDES AND THEIR REACTIONS
2255
Table 1 Activation parameters for the reaction of N-(phenylsulfinyl)phthalimide in dioxane with sodium ethox-
ide, sodium methoxide, methylamine, and t-butylamine
Nucleophile
ꢀH= (kJ/mol)
ꢀS= (J/molK)
R2
Sodium methoxide
Sodium ethoxide
t-Butylamine
41.01
37.62
36.99
37.29
−79.53
−90.97
−139.2
−135.1
0.996
0.999
0.991
0.971
Methylamine
described by Harpp and Back.5 N-(p-Substitutedarylthio)phthalimides were prepared from
the corresponding p-substitutedthiophenol by reaction with phthalimide in hot acetonitrile
and pyridine then a solution of bromine in acetonitrile, as described by Klose, Reese, and
Song.14 All melting points were determined using an electrothermal digital melting point
apparatus.
1a m.p. 191 ◦C –192 ◦C (lit.5 191–194 ◦C); found C, 62.99; H, 4.11; N, 4.98; calc.
for C15H11NSO3 C, 63.14; H, 3.89; N, 4.91%;
1b m.p. 150–153.5 ◦C (lit.5 150 ◦C –153 ◦C); found C, 61.71; H, 3.37; N, 4.83; calc.
for C14H9NSO3 C, 61.98; H, 3.34; N, 5.16%;
1c m.p. 212 ◦C –213 ◦C; found C, 55.31; H, 2.60; N, 4.78; calc. For C14H8NSO3Cl C,
55.00; H, 2.64; N, 4.58%; IR υ = 3084 cm−1 (C-H), 1609–1467 cm−1 (C C), 1108 cm−1
1
(C-N), 1090 cm−1 (S-O), 711 cm−1 (Ar–Cl), 685 cm−1 (C-S); H NMR (CDCl3): δ =
8.13–8.09 (dd, 2H, J = 1.62 Hz), 8.02–7.98 (dd, 2H, J = 2.24 Hz), 7.78–7.71 (d, 2H, J =
3.18 Hz), 7.68–7.63 (d, 2H, J = 4.13 Hz); 13C NMR (CDCl3): δ = 165.1, 139.3, 138.6,
135.3, 131.5, 129.8, 126.7 124.7.
Table 2 Values of k2 (M−1s−1) for the substitution of N-(p-substitutedarylsulfinyl)phthalimides with nucle-
ophiles at 30.0 0.1 ◦C in dioxane
Nucleophile
Substituent
k2 (M−1s−1
)
Sodium ethoxide
CH3O
CH3
H
23.72
39.38
45.21
58.93
209.76
25.57
30.06
42.92
50.65
151.92
0.110
0.114
0.158
0.331
3.750
0.130
0.124
0.211
0.257
0.635
Cl
NO2
CH3O
CH3
H
Sodium methoxide
t-Butylamine
Cl
NO2
CH3O
CH3
H
Cl
NO2
CH3O
CH3
H
Cl
NO2
Methylamine

2256
Y. S. BOZKURT AND H. KUTUK
1d m.p. 181 ◦C–184 ◦C; found C, 59.53; H, 3.59; N, 4.54; calc. for C15H11NSO4 C,
59.79; H, 3.68; N, 4.65%; IR υ = 3084 cm−1 (C-H), 1601–1466 cm−1 (C C), 1197 cm−1
1
(C-N), 1062 cm−1 (S-O), 604 cm−1 (C-S); H NMR (CDCl3): δ = 7.91–7.86 (dd, 2H, J
= 3.02 Hz), 7.79–7.78 (d, 2H, J = 3.73 Hz), 7.76–7.71 (dd, 2H, J = 2.38 Hz), 6.86–6.82
(d, 2H, J = 5.10 Hz), 3.78 (3H, CH3O); 13C NMR (CDCl3): δ = 167.8, 161.4, 136.7, 134.5,
132.0, 125.3, 123.9, 114.6, 55.4.
1e m.p. 175 ◦C –178 ◦C; found C, 54.00; H, 2.49; N, 8.75; calc. for C14H8N2SO5 C,
54.16; H, 2.55; N, 8.86%; IR υ = 3052 cm−1 (C-H), 1610–1542 cm−1 (C C), 1494 cm−1
1
(C-NO2), 1198 cm−1 (C-N), 1100 cm−1 (S-O), 552 cm−1 (C-S); H NMR (CDCl3): δ =
8.18–8.14 (d, 2H, J = 4.32 Hz), 8.04–7.98 (dd, 2H, J = 3.86 Hz), 7.92–7.85 (dd, 2H, J =
2.73 Hz), 7.42–7.38 (d, 2H, J = 3.14 Hz); 13C NMR (CDCl3): δ = 167.0, 146.8, 144.6,
135.3, 131.6, 125.7, 124.5, 124.4.
Kinetic Studies
The rates of substitution reactions of N-(p-substituted-arylsulfinyl)phthalimides were
followed spectrophotometrically using a GBC Cintra 20 Model UV-VIS spectrophotometer
with a thermostatted cell compartment ( 0.05 ◦C). The values of k1 were calculated from
the standard equation using a least-squares procedure. All kinetic measurements were
duplicated, and the average deviation from the mean was <3%. Second-order rate constants
(k2) were calculated from the slope of the plots of pseudo-first-order rate constants versus
nucleophile concentrations (at least five different concentrations).
Product Analysis
Sodium methoxide (0.09 g, 1.67 mmol) was added to p-toluenesulfinylphthalimide
(0.48 g, 1.67 mmol) in dioxane. The reaction mixture was stirred for seven days at room
temperature. Dioxane was evaporated in vacuo. The reaction mixture was poured out
anhydrous ether (20 mL). Insoluble material was then filtered. Ether was evaporated in
vacuo. The resulting colorless oil was treated with chloroform. White solid was filtered.
Chloroform was evaporated in vacuo. Methyl p-toluenesulfinate was obtained (0.22 g, 77%)
as colorless oil. nD = 1.5420, lit.15 nD = 1.5416; 1H NMR (CDCl3): δ = 7.55–7.51 (d,
2H, J = 8.14 Hz), 7.30–7.26 (d, 2H, J = 8.23 Hz), 3.38 (3H,−OCH3), 2.36 (3H, -CH3);
13C NMR (CDCl3): δ = 138.8, 134.2, 128.0, 124.6, 67.1, 21.3.
21
21
Analysis of the products also was determined by comparing the UV spectrum obtained
after completion of the kinetic experiment with the spectrum of the expected products at
the same concentration and under the same conditions. Thus, for the reaction of N-(p-
toluenesulfinyl)phthalimide with sodium methoxide, the UV spectrum recorded at the end
of the reaction was identical with that of a 1:1 mixture of sodium phthalimide and methyl
p-toluenesulfinate.
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THE SYNTHESIS OF SULFINYLPHTHALIMIDES AND THEIR REACTIONS
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