A comparative study of the effect of water and organic solvents on 1,3-dipolar cycloaddition reactions of mesitonitrile oxide with c-sulfonyl- and sulfanyl-dithioformates

Article abstract of DOI:10.1080/10426500903427700

1,3-Dipolar cycloadditions of the C-sulfonylated- and sulfanylated- dithioformates with mesitonitrile oxide occurred smoothly in organic and aqueous media to afford 1,4,2-oxathiazoles in good yields. The structures of these cycloadducts have been establis

Full text of DOI:10.1080/10426500903427700

This article was downloaded by: [Portland State University]
On: 15 October 2014, At: 14:55
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
A Comparative Study of the Effect of
Water and Organic Solvents on 1,3-
Dipolar Cycloaddition Reactions of
Mesitonitrile Oxide with C-Sulfonyl- and
Sulfanyl-Dithioformates
Ibrahim El-Sayed a , Omar M. Ali a , Mohamed A. Hawata a & Sally
Abou Hegazey a
a Chemistry Department, Faculty of Science , El-Menoufeia
University , Shebin El-Koom, Egypt
Published online: 25 Aug 2010.
To cite this article: Ibrahim El-Sayed , Omar M. Ali , Mohamed A. Hawata & Sally Abou Hegazey
(2010) A Comparative Study of the Effect of Water and Organic Solvents on 1,3-Dipolar Cycloaddition
Reactions of Mesitonitrile Oxide with C-Sulfonyl- and Sulfanyl-Dithioformates, Phosphorus, Sulfur, and
Silicon and the Related Elements, 185:9, 1979-1985, DOI: 10.1080/10426500903427700
To link to this article: http://dx.doi.org/10.1080/10426500903427700
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 185:1979–1985, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903427700
A COMPARATIVE STUDY OF THE EFFECT OF WATER
AND ORGANIC SOLVENTS ON 1,3-DIPOLAR
CYCLOADDITION REACTIONS OF MESITONITRILE OXIDE
WITH C-SULFONYL- AND SULFANYL-DITHIOFORMATES
Ibrahim El-Sayed, Omar M. Ali, Mohamed A. Hawata,
and Sally Abou Hegazey
Chemistry Department, Faculty of Science, El-Menoufeia University,
Shebin El-Koom, Egypt
1,3-Dipolar cycloadditions of the C-sulfonylated- and sulfanylated-dithioformates with mesi-
tonitrile oxide occurred smoothly in organic and aqueous media to afford 1,4,2-oxathiazoles
in good yields. The structures of these cycloadducts have been established via the analysis
of NMR data and elemental analyses.
Keywords 1,3-Dipolar cycloaddition; mesitonitrile oxide; 1,4,2-oxathiazole derivatives; sul-
fanyldithioformates; sulfonyl dithioformates
INTRODUCTION
1,3-Dipolar cycloaddition reactions of nitrile oxides have found many useful applica-
tions in organic synthesis, particularly with respect to the synthesis of compounds with new
chiral centers.1,2 Such asymmetric syntheses have a growing importance in the pharmaceu-
tical and agricultural industries with respect to the preparation of chiral drugs and natural
products.3 Also, beyond the capability of the 1,3-dipolar cycloadditon reaction to produce
heterocycles, the ability of heteroatom-containing cycloadducts to transform into a variety
of other functionalized organic molecules, cyclic or acyclic, has been reported.4 There also
has been wide interest in the 1,3-dipolar cycloaddition reactions of thione dipolarophiles.5
The >C S double bond displays an unusually high reactivity with a number of 1,3-dipoles,
and because of this, thiones have been regarded as super-dipolarophiles. In this context, C-
sulfonylated- and sulfanylated-dithioformates 5 and 9 are versatile thiocarbonyl reagents,
and they have received much of our attention due to their numerous synthetic applica-
tions.5,6 Recently, we have reported the cycloaddition reactions of 5 toward 1,3-dienes and
diazoalkanes.5,b,c However, to the best of our knowledge, the chemistry of and information
on the 1,3-dipolar cycloaddition of 5 and 9 to nitrile oxides are scant and deserve further
investigation.7 Another intriguing point to be addressed in this 1,3-dipolar cycloaddition
Received 7 July 2009; accepted 20 October 2009.
Partial financial support from Danish International Development Agency (DANIDA) is highly appreciated.
Address correspondence to Prof. Ibrahim El-Sayed, Chemistry Department, Faculty of Science,
El-Menoufeia University, Shebin El-Koom, Egypt. E-mail: ibrahimtantawy@yahoo.co.uk
1979

1980
I. EL-SAYED ET AL.
reactions is to investigate the use of water as an environmentally friendly alternative to
organic solvents, and efforts in this field are certainly worthwhile. More specifically, we are
interested to know how water affects this reaction and whether or not water is generally a
favorable reaction medium. Another aim in this work is to compare the dipolarophilicity of
the >C S group of sulfonyldithioformates 5 and sulfanyldithioformates 9 in organic and
aqueous media.
RESULTS AND DISCUSSION
We have chosen the C-sulfonylated- and C-sulfanylated-dithioformates 5 and 9,
respectively, as thiocarbonyl-based dipolarophiles for the present study because the
dipolarophilicity of thiocarbonyl group strongly depends on the nature of the sub-
stituents at the thiocarbonyl carbon atom. Thus, the starting S-pentachlorophenyl C-
arylsulfonyldithioformates 5 were prepared in good yields in a two-step procedure as
described by us, starting from thiophosgene and pentachlorothiophenol 2, and subsequent
reaction of chlorodithioformates 3 with sodium sulfinates 4 in water/benzene in the pres-
ence of tetrabutylammonium hydrogen sulfate afforded 5 in 60–80% yields8 as depicted in
Scheme 1.
S
ArSO2Na
S
S
NaOH
CHCl3
4
C
C
C
C6Cl5SH
+
Cl
C6Cl5S
SO2Ar
C6Cl5S
TBAHS
benzene/water
Cl
Cl
5
1
2
3
a: Ar = C6H5; b: Ar = 4-CH3C6H4
c: Ar = 4-ClC6H4
Scheme 1
The mesitonitrile oxide 6 was chosen for the aforementioned cycloadditions as one
of the most stable nitrile oxides with minimum side reactions.9 It was generated from the
corresponding mesitaldehyde via sequential oxime formation, N-chlorosuccinimide (NCS)
chlorination, and dehydrochlorination of the corresponding hydroximoyl chloride in the
presence of triethylamine as a base according to Scheme 2.
H
C
Cl
C
NCS
NaOH
R
N
OH
R
N OH
+
NH2OH.HCl
R
CHO
DMF
C2H5OH/H2O
Et3N
N
DMF
R = 2,4,6-(CH3)3C6H2
R
C
O
6
Scheme 2
At room temperature, a methylene chloride solution of 5 reacts with mesitonitrile
oxide 6 immediately within 10 min as judged by both TLC analysis and the discharge
of the red color of 5. NMR analysis of the crude products revealed that the cycloadducts

CYCLOADDITION REACTIONS OF MESITONITRILE OXIDE
1981
1,4,2-oxathiazoles 7 had been formed in good yields as a stable, white, crystalline product
as depicted in Scheme 3.
R
S
S
ArSO2
C6Cl5S
CH2Cl2
C6Cl5S C SO2Ar
+
R
N
O
C
N
rt, 10 mints.
O
5
6
7
a: Ar = C6H5; b: Ar = 4-CH3C6H4
c:Ar = 4-ClC6H4
R = 2,4,6-(CH3)3C6H2
Scheme 3
As expected for 1,3-dipolar reactions, the sulfonyl group at the thiocarbonyl carbon
atom of 5 enhanced the dipolarophilic reactivity towards cycloaddition considerably. In the
structure proof of the cycloadducts 7, the 13C NMR analysis showed a signal at around
156 ppm, which is consistent with the assignment to the imine carbon of the oxathiazole
ring. In order to compare the influence of the electron-withdrawing substituent on the
dipolarophilic reactivity of the thiocarbonyl group of 5, we have further examined the same
reaction with sulfanylated dithioformates 9. The starting thiocarbonyl compounds 9a and
9b needed for this study were prepared in good yields (see the Experimental section) by the
reaction of chlorodithioformates 3 with thiolates 8 as depicted in Scheme 4. This synthesis
included an optimization of a previously reported method.10 Employing sodium hydride as
a base instead of NaOH, greatly facilitates the reaction by drastically reducing the time for
completion from one week to a few hours and at the same time improves the yield greatly.
S
S
NaH
C
C
ArSH
+
C6Cl5S
Cl
C6Cl5S
CH2Cl2
rt., 2h
SAr
8
3
9
a: Ar = 4-ClC6H4
b: Ar =2,4,5-Cl3C6H2
Scheme 4
The 13C NMR signal of the >C S group of 9a and 9b resonates at 212.2 and 216.5
ppm, respectively, and a downfield shift of 23 to 27 ppm from the starting chlorodithio-
formates 3 (189 ppm)8 occurred. With sulfanylated dithioformates in hand, 1,3-dipolar
cycloaddition reactions of 9 with mesitonitrile oxide 6 were then conducted. Treatment
of 9 with mesitonitrile oxide 6 at room temperature in dichloromethane for 3 h afforded
the corresponding cycloadducts 1,4,2-oxathiazoles 10 in good yields after purification (see
Scheme 5).
The adducts 10 are stable to the reaction conditions, and they are characterized as
1,4,2-oxathiazoles on the basis of their NMR spectra and elemental analysis (see the Ex-
perimental section). Thus, the imine carbons (identified by their 13C NMR) led to carbon
resonances correctly predicted to be 156.31 and 157.34 ppm for 10a and 10b, respectively,

1982
I. EL-SAYED ET AL.
R
S
S
C6Cl5S
ArS
CH2Cl2
rt, 3 h.
C6Cl5S C SAr
+
R
N
O
C
N
O
9
6
10
a: Ar = 4-ClC6H4
b: Ar = 2,4,5-Cl3C6H2
R = 2,4,6-(CH3)3C6H2
Scheme 5
and within the normal range of the quaternary imine carbon. This result clearly shows
the activating effect of the sulfonyl group on the dipolarophilic character of the thiocar-
bonyl function of 5. In an attempt to replace potentially hazardous dichloromethane with
environmentally benign solvents such as water or other eco-friendly alternatives, we have
performed the cycloaddition in water. Primarily we wanted to know how water affects this
reaction and whether or not water is generally a favorable reaction medium. After 3 h of
stirring a suspension of solids 5 and 6 in water at ambient temperature, the reaction was
completed as monitored by the TLC and the discharge of the red color of 5. After com-
pletion of the reaction, the product settles to the bottom and can then be obtained simply
by pouring the water off. The NMR and TLC analysis of the product proved the formation
of the cycloadducts 7. However, when we performed the same reaction with 9, only 50%
conversion of the starting materials into the corresponding cycloadducts 10 was observed
after 2 h. Interestingly, using water mixed with ethanol as cosolvent led to the complete
conversion of 9 to 10.
CONCLUSION
In conclusion, we showed that our main goal, which was to replace harmful solvents
by water as an environmentally benign alternative, could be achieved. In addition, aqueous
media also offer advantages in terms of easy isolation of products. However, there are
some drawbacks such as modest yields and low reaction rates. This maybe due to the lower
water solubility of the reactants. Understanding the modes of interaction of water with the
reactants and enhancing the solubility of the starting materials are currently underway in
our laboratory.
EXPERIMENTAL
All 1H and 13CNMR experiments (solvent CDCl3) were carried out with a 400 MHz
Bruker Avance DRX-400 spectrometer (400 MHz for 1H, 100 MHz for 13C) at University
of Antwerp, Belgium. Chemical shifts are reported in part per million (ppm) relative to
the respective solvent or tetramethylsilane (TMS). Melting points were recorded on Stuart
scientific melting point apparatus and are uncorrected. The microanalysis was performed
in the Microanalysis Laboratory at Cairo University. All reactions were followed by thin
layer chromatography (TLC) on Kiesel gel F254 precoated plates (Merck). Solvents were
dried/purified according to procedures in ths literature. Pentachlorophenyldithioformate
3, C-sulfonylated dithioformates 5, and mesitonitrile oxide 6 were prepared according to
procedures in the literature.8,9

CYCLOADDITION REACTIONS OF MESITONITRILE OXIDE
1983
General Procedure for the Synthesis of Arylsulfanyldithioformates 9
The thiol 8 was dissolved in a small portion of dry dichloromethane (5 mL), and
sodium hydride (166 mg, 3.93 mmol) was added portionwise at 0◦C. After 10 min, pen-
tachlorophenyl chlorodithioformates 3 (500 mg, 180.50 mmol) dissolved in 5 mL dry
dichloromethane was added dropwise to the above mentioned mixture at room temperature
over a period of 10 min. The resulting solution was stirred overnight at room temperature.
The dichloromethane solution was washed with water (three times). The organic layer was
dried over anhydrous CaCl2, filtered, and then concentrated under reduced pressure to leave
an oily residue, which was precipitated with n-hexane. This was then recrystallized from
n-hexane to yield pure 9.
Pentachlorophenyl C-(4-chlorophenylsulfanyl)dithioformate 9a. Yield:
82%, yellow crystals, melting point, as well 1H and 13C MNR data are in agreement with
those reported in the literature.6
Pentachlorophenyl C-(2,4,5-trichlorophenylsulfanyl)dithioformate 9b.
Yield: 80%, yellow crystal, mp 72–75◦C. IR (KBr): 3075(υC H,Ar), 1560 (υC C,Ar),
1
1093(υC S); 781 (υC Cl). H NMR (CDCl3): δ = 7.50 (s, 1H, Ar); 7.68 (s, 1H, Ar). 13C
NMR (CDCl3); δ 128.88; 131.10; 131.94; 132.72; 132.95; 133.14; 137.06; 138.25; 138.74;
139.10; 212.22 (>C S).
3-Mesityl-5-(phenylsulfonyl)-5-pentachlorophenylthio
(1,4,2-oxathiazole) 7a
The pentachlorophenyl C-(phenylsulfonyl)dithioformate 5a (50 mg, 0.107 mmol)
was dissolved in a small portion of dichloromethane (5mL), and mesitonitrile oxide 6
(17.25 mg, 0.107 mmol) was added. The violet color of 5a disappeared after 10 min, and
the solvent was evaporated under reduced pressure to leave a semisolid residue, which
was precipitated by washing with diethyl ether to give white crystals. Yield: 73%, mp:
130–132◦C. 1H NMR (CDCl3): δ 1.90 (s, 3H, CH3); 2.27 (s, 6H, 2CH3); 6.81 (s, 2H); 7.65
(d, 2H, J = 8.4 Hz); 7.83 (m, 1H); 8.15 (d, 2H, J = 8.8 Hz). 13C NMR (CDCl3): δ 22.8;
24.9; 120.13; 128.0; 129.50; 129.60; 132.50; 133; 133.20; 135.30; 136.10; 137.40; 138.60;
140.50; 142.10; 156.15 Calcd: C, 41.76; H, 2.21; N, 2.03 for C12H15C16NO3S3. found: C,
41.71; H, 2.28; N, 2.11.
3-Mesityl-5-tolysulfonyl-5-pentachlorophenylthio(1,4,2-oxathiazole) 7b
1
The procedure as given for 7a was followed. Yield 69%, mp 76–78◦C, H NMR
(CDCl3): δ 1.92 (s, 3H, CH3); 2.25 (s, 6H, 2CH3); 2.51 (s, 3H, CH3); 6.81 (s, 2H); 7.44 (d,
2H, J = 9.3 Hz); 8.07 (d, 2H. J = 8.1 Hz). 13C NMR (CDCl3): δ 22.8; 24.30; 24.9; 120.78;
128.0; 128.20; 129.60; 130; 132.50; 133; 133.20; 135.9; 136.10; 138.60; 140.50; 143.40;
156.13. Calcd.: C, 44.91; H, 2.83; N, 2.18. for C24H18C15NO3S3: found: C, 44.40; H, 2.60;
N, 2.08.
3-Mesityl-5-(4-chlorophenylsulfonyl)-5-pentachlorophenylthio
(1,4,2-oxathiazole) 7c
The procedure as given for 7a was followed. Yield: 82%, mp 140–142◦C, 1H NMR
(CDCl3): δ 1.91 (s, 3H, CH3); 2.24 (s, 6H, 2CH3); 6.80 (s, 2H); 7.63–8.21 (m, 4H). 13C
NMR (CDCl3): δ 22.8; 24.9; 120.20; 128.0; 128.30; 129.60; 129.80; 132.60; 133; 133.20;

1984
I. EL-SAYED ET AL.
133.80; 136.10; 138.60; 138.90; 140.50; 142.10; 156.03. Calcd.: C, 41.71; H, 2.28; N, 2.11.
for C23H15C16NO3S3: found: C, 41.76; H, 2.21; N, 2.03.
3-Mesityl-5-p-chlorophenylthio-5-pentachlorophenylthio
(1,4,2-oxathiazole) 10a
The pentachlorophenyl C-(4-chlorophenylsulfanyl)dithioformate 9a (50 mg,
0.106 mmol) was dissolved in dichloromethane (5 mL), and mesitonitrile oxide (17.10 mg,
0.106 mmol) was added. The reaction mixture was stirred for 3 h and concentrated
under reduced pressure to leave a semisolid residue, which was precipitated by washing
1
with ether to give white crystals, Yield: 59%, mp 138–140◦C, H NMR (CDCl3): δ 1.85
(s, 3H, CH3); 2.20 (s, 6H, 2CH3); 6.70 (s, 2H); 7.40 (d, 2H); 7.60 (d, 2H).13C NMR
(CDCl3): δ 18.8; 21.11; 119.45; 121.74; 128.44; 128.54; 128.69; 128.96; 129.21; 129.66;
136.32; 136.83; 137.52; 138.34; 140.31; 156.31. Calcd: C, 43.83; H, 2.40; N, 2.22 for
C23H15Cl6NOS3. found: C, 43.51; H, 2.27; N, 2.07.
3-Mesityl-5-(2,4,5-trichlorophenylthio-5-pentachlorophenylthio
(1,4,2-oxathiazole) 10b
The procedure as given for 9a was followed. Yield: 57%, mp 152–154◦C. 1H NMR
(CDCl3): δ 2.00 (s, 3H, CH3); 2.25 (s, 6H, 2CH3); 6.83 (s, 2H); 7.62 (s, 1H); 8.01 (s,
1H.). 13C NMR (CDCl3): δ 18.94; δ 21.17; 120.18; 121.15; 128.21; 128.65;129.88; 129.96;
130.08, 131.11; 131.46; 132.61; 135.43; 137.07; 137.46; 138.39; 141.39; 157.34. Calcd:
C, 38.23; H, 1.69; N, 1.71 for C23H13C18NOS3. found: C, 39.51; H,1.87; N, 2.00.
General Procedure for 1,3-Dipolar Cycloadditions of C-Sulfonylated-
dithioformates 5 in Water
A mixture of 5 (0.10 mmol), mesitonitrile oxide 6 (0.12 mmol), and water (2 mL)
was left stirring at room temperature. After 3 h, the red color of 5 had vanished, and a white
product precipitated. The solid was filtered, washed with cold water, and dried to afford
the cycloadducts 7, in 70–80% yields. The NMR data are consistent with the structure of
cycloadducts 7.
General Procedure for 1,3-Dipolar Cycloadditions of C-Sulfanyl-
dithioformates 9 in Ethanol/Water Mixture
In a mixture of 1.6 mL of 1:1 (v/v) ethanol/water, 0.10 mmol of 9 and 0.12 mmol
of 6 were suspended, and the mixture was left stirring at room temperature. After 2 h,
the yellow color of 9 had disappeared and a white solid had precipitated. The solid was
filtered, washed with cold water, and dried to yield the cycloadducts 10 in 65–70% yields.
The NMR data of 10 are consistent with the structure of cycloadducts obtained in organic
solvent.
REFERENCES
1. L. I. Belen’kii, In Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis: Novel Strategies
in Synthesis, 2nd ed., H. Feuer, Ed. (John Wiley & Sons, Hoboken, NJ, 2008), p. 1.

CYCLOADDITION REACTIONS OF MESITONITRILE OXIDE
1985
2. V. Ja¨ger and P. Colinas, In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward
Heterocycles and Natural Products, A. Padwa and W. H. Pearson, Eds. (John Wiley & Sons,
New York, 2002), p. 361.
3. G. Mloston and H. Heimgartner, in The Chemistry of Heterocyclic Compounds, Vol. 59: Synthetic
Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products,
A. Padwa and W. H. Pearson, Eds. (John Wiley & Sons, New York, 2002, p. 315.
4. G. Mloston´ and H. Heimgartner, In Targets in Heterocyclic Systems—Chemistry and Properties,
O. A. Attanasi and D. Spinelli, Eds. (Italian Society of Chemistry, Rome, 2006), vol. 10, p. 266.
5. (a) K. Urbaniak, M. Sobieraj, G. Mloston´, A. Linden, and H. Heimgartner, Heterocycles, 65,
1373 (2005); (b) I. El-Sayed, O. Aly, A. Fischer, and A. Senning, Heteratom Chem., 14, 170
(2003); (c) A. Khattab, O. Ali, and I. El-Sayed, Heteratom Chem., 18, 28 (2007), and references
cited therein.
6. I. El-Sayed, K. M. H. Hilmy, S. M. El-Kousy, A. Fischer, and H. Slem, Phosphorus, Sulfur, and
Silicon, 178, 2403 (2003), and references cited therein.
7. (a) S. Holm, J. A. Boerma, H. N. Nilsson, and A. Senning, Chem. Ber., 109, 1069 (1976); (b) R.
Huisgen, W. Mack, and E. Anneser, Angew. Chem., 73, 656 (1961).
8. I. El-Sayed, M. Abdel-Megeed, S. Yassin, and A. Senning, Sulfur Rep., 16, 235 (1995), and
references cited therein.
9. C. Grundmann and J. M. Dean, J. Org. Chem., 30, 2809 (1965).
10. H. C. Godet and R. E. Wann, J. Org. Chem., 26, 4047 (1961).