Synthesis of the 1,3-oxathiolanes using asymmetrically oxiranes

Article abstract of DOI:10.1016/j.cclet.2011.05.021

An efficient synthesis of 1,3-oxathiolane-2-imin derivatives is described via one-pot reaction between arylisothiocyanats, asymmetrically substituted oxiranes and catalytic amount of methanol. The mild reaction conditions and high yields of the products e

Full text of DOI:10.1016/j.cclet.2011.05.021

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Chinese Chemical Letters 22 (2011) 1143–1146
www.elsevier.com/locate/cclet
Synthesis of the 1,3-oxathiolanes using asymmetrically oxiranes
b
c
Faramarz Rostami-Charati a, , Zinatossadat Hossaini , Bita Mohtat ,
*
Mehdi Shahraki d, Mohammad R. Hosseini-Tabatabaei d
a Department of Chemistry, Facualty of Science, Gonbad Kavous University, P.O. Box 163, Gonbad, Iran
b Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
c Department of Chemistry, Islamic Azad University, Karaj Branch, Karaj, Iran
d Islamic Azad University, Zahedan Branch, Zahedan, Iran
Received 24 February 2011
Available online 20 July 2011
Abstract
An efficient synthesis of 1,3-oxathiolane-2-imin derivatives is described via one-pot reaction between arylisothiocyanats,
asymmetrically substituted oxiranes and catalytic amount of methanol. The mild reaction conditions and high yields of the products
exhibit the good synthetic advantage of this method.
# 2011 Faramarz Rostami-Charati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 1,3-Oxathiolane-2-imine; Oxirane; Methanol; One-pot reactions; Arylisothiocyanats
Because of the strain induced by the presence of a three membered ring (having a high thermodynamic driving
force, usually greater than 20 kcal/mol) [1], epoxides are significantly more reactive than to other ethers. Thus, they
become as useful building block compounds in organic synthesis. Synthetic procedures for epoxide ring opening can
be based on nucleophilic or protic/Lewis acid-mediated electrophilic ring opening [2,3]. A number of procedures
which feature the oxyphilic Lewis character of metal ions and non-metallic Lewis acids have been developed. Suitable
epoxide opening catalysts include Lewis acids, Lewis bases, Bronsted acids, thioxanthenone-fused azacrown ethers,
Schiff base and porphyrin complexes [3–14]. The regioselectivity has been found to be in many cases sensitive to the
operating opening reactions, that is, if these were carried out under standard or chelating conditions [15–17].
Although, the use of chelating opening conditions affords a nice regioalternating process but the method is limited to
the epoxides bearing chelate-forming substituents. Also, compounds containing an imine group are increasingly
important in organic synthesis [18] and the mechanism of the cis/trans isomerization of imines is being studied in
detail [19]. The 1,3-oxathiolane-2-imine structures include an exocyclic imine group and can be used in organic
synthesis for the preparation of biologically active compounds. As part of our current studies on the development of
new routes in heterocyclic synthesis, we report an efficient procedure for direct synthesis of 1,3-oxathiolan derivatives
3 from the reaction of epoxide 1 and arylisothiocyanate 2 in the presence of catalytic amount of methanol and NaH
under solvent-free conditions at 50 8C in excellent yield (Scheme 1).
* Corresponding author.
E-mail address: f_rostami_ch@yahoo.com (F. Rostami-Charati).
1001-8417/$ – see front matter # 2011 Faramarz Rostami-Charati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.05.021

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F. Rostami-Charati et al. / Chinese Chemical Letters 22 (2011) 1143–1146
NAr
MeOH(20 mol%)
O
NaH (10 mol%)
O
S
+
Ar-N=C=S
Solvent-free, 50oC
R
R'
R'
R
3
2
1
Scheme 1. One-pot reaction of epoxide and arylisothiocyanate in the presence of catalytic amount of methanol.
Structures of compounds 3a–k were assigned by IR, 1H NMR, 13C NMR and mass spectral data (Fig. 1) [20]. Due
to the presence of a stereogenic center, the 1H NMR spectrum of 3a exhibited three multiplets at 3.50–3.58, 4.24–4.34
and 5.01–5.07 ppm arising from two CH2 and CH protons, respectively. The 13C NMR spectrum of 3a appears 12
signals agreement with proposed structure. The mass spectrum of 3a displayed the molecular ion peak at m/z 285.
Although the mechanistic details of the reaction are not known, a plausible rationalization may be advanced to explain
the product formation (Scheme 2). Presumably, the anionic intermediate A formed from the reaction of 2 with
methoxide anion. After that by nucleophilic attacking of A to oxirane derivatives 1, intermediate B was produced.
Eventually the intermediate B can undergo cyclization under the employed reaction conditions to producing of
intermediate C followed by losing of methoxy group, the product of 3 was generated.
PhOH2C
PhOH2C
O
S
O
S
H 3C
O
S
PhOH2C
O
S
N
N
Me
N
N
OMe
H
H
H
H
3d(87%)
3c(88%)
3a(90%)
3b(92%)
(H3 C) 2 HCOH2C
O
S
(H3C)2HCOH2C
H3C
O
S
O
H3C
O
N
S
N
N
Me
N
OMe
Me
S
H
H
H
H
3g(89%)
3h(89%)
3f(86%)
3e(85%)
(H3C)2HCOH2C
O
S
H3CH2CH2C
H
O
S
H3CH 2CH 2C
O
S
N
OMe
N
Me
N
OMe
H
H
3i(87%)
3j(86%)
3k(87%)
Fig. 1. Structures of compounds 3a–k.
MeOH NaH
+
NAr
O
S
Ar
N
C
S
MeO
Na
2
R'
R
3
NAr
MeO
MeO
NAr
O
S
S
Int-A
NAr
MeO
R'
O
R
Int-c
S
R
O
R'
1
R
R'
Int-B
Scheme 2. Possible mechanism for the formation of products 3.

F. Rostami-Charati et al. / Chinese Chemical Letters 22 (2011) 1143–1146
1145
In conclusion, we have developed the most useful and dependable procedure currently available for the synthesis of
1,3-oxathiolane-2-imine by using low cost and readily available starting materials in one-pot. This method represents a
simple and green procedure, uses mild reaction conditions, and has general applicability. It avoids hazardous organic
solvents and toxic catalysts and gives nearly quantitative yields without any by-products in most cases.
Acknowledgments
We gratefully acknowledge support of this research work by Islamic Azad University of Qaemshahr and the
University of Gonbad Kavous.
References
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[12] H. Naeimi, M. Moradian, Can. J. Chem. 84 (2006) 1575.
[13] H. Eshghi, M. Rahimizadeh, A. Shoryabi, J. Iran. Chem. Soc. 2 (2005) 155.
[14] H. Sharghi, A.H. Nejad, Phosphorus Sulfur 179 (2004) 2297.
[15] P. Crotti, V.D. Bussolo, L. Favero, et al. Tetrahedron 56 (2000) 7513.
[16] D.O. Arbelo, J.A. Prieto, Tetrahedron Lett. 43 (2002) 4111.
[17] E.N. Jacobsen, F. Kakiuchi, R.G. Konsler, et al. Tetrahedron Lett. 38 (1997) 773.
[18] (a) G. Borg, M. Chino, J.A. Ellman, Tetrahedron Lett. 42 (2001) 1433;
(b) K.B. Sharpless, Org. Lett. 1 (1999) 783;
(c) G. Alvaro, G. Martelli, D. Savoia, A. Zoffoli, Synthesis (1998) 1773.
[19] J.E. Johnson, N.M. Morales, A.M. Gorszyca, et al. J. Org. Chem. 66 (2001) 7979.
[20] General procedure for preparation of compounds 3a–k: A mixture of methanol (20 mol%) and NaH (10 mol%) was stirred for 10 min. Then,
arylisothiocyanate derivatives 2 (2 mmol) was gently added and warmed at about 50 8C for 2 h. Then, after addition of oxirane derivatives 1
(2 mmol) the reaction mixture was stirred for 4 h. After completion of the reaction (monitored by TLC), the mixture of reaction was purified by
column chromatography (SiO2; n-hexane/AcOEt 9:1) to afford pure title compounds. N-(5-Methyl-1,3-oxathiolan-2-ylidene)benzenamine
(3a): Yellow powder, yield: 0.51 g (90%). IR (KBr) (nmax/cmÀ1): 2928, 1735, 1644, 1483, 1234 and 1072. 1H NMR (500 MHz, CDCl3): d 3.50–
3.59 (m, 2 H, CH2), 4.24–4.35 (m, 2 H, CH2), 5.01–5.05 (m, 1 H, CH), 6.96–7.38 (m, 10 H, 10 CH). 13C NMR (125.7 MHz, CDCl3): d 33.5
(CH2), 66.9 (CH2), 78.9 (CH), 114.6 (2 CH), 121.2 (2 CH), 121.7 (CH), 124.4 (CH), 129.1 (2 CH), 129.6 (3 CH), 148.9 (C), 158.0 (C), 162.9
(C). Anal. Calcd. for C16H15NO2S (285.36): C, 67.35, H, 5.30, N, 4.91. Found: C, 67.23, H, 5.21, N, 4.85. 4-Methyl-N-(5-methyl-1,3-
oxathiolan-2-ylidene)benzenamine (3b): Yellow powder, yield: 0.55 g (92%). IR (KBr) (nmax/cmÀ1). 2972, 1652, 1593, 1481, 1373 and 1266.
1H NMR (500 MHz, CDCl3): d 2.36 (s, 3 H, Me), 3.49–3.58 (m, 2 H, CH2), 4.25–4.28 (m, 1 H, CH), 4.32–4.34 (m, 1 H, CH), 4.99–5.04 (m, 1 H,
CH), 6.91 (d, 2 H, 3J = 8.2 Hz, 2 CH), 6.96 (d, 2 H, 3J = 8.3 Hz, 2 CH), 7.02 (t, 1 H, 3J = 7.3 Hz, CH), 7.16 (d, 2 H, 3J = 8.2, 2 CH), 7.33 (t, 2 H,
3J = 7.9 Hz, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 20.9 (Me), 33.5 (CH2), 66.9 (CH2), 78.9 (CH), 114.7 (2 CH), 121.0 (2 CH), 121.7 (CH),
129.6 (2 CH), 129.7 (2 CH), 133.9 (C), 146.4 (C), 158.1 (C), 162.6 (C). Anal. Calcd. for C17H17NO2S (299.39): C, 68.20, H, 5.72, N, 4.68.
Found: C, 68.25, H, 5.83, N, 4.75. 4-Methoxy-N-(5-methyl-1,3-oxathiolan-2-ylidene)benzenamine (3c): Pale yellow powder, yield: 0.45 g
(89%). IR (KBr) (nmax/cmÀ1): 2974, 1642, 1590, 1481, 1373 and 1118. 1H NMR (500 MHz, CDCl3): d 1.22 (d, 6 H, 3J = 6.2, 2 Me), 3.34–3.42
(m, 2 H, CH2), 3.62–3.70 (m, 3 H, 3 CH), 4.76–4.77 (m, 1 H, CH), 6.98 (d, 2 H, 3J = 7.6, 2 CH), 7.12 (t, 1 H, 3J = 7.4, CH), 7.33 (t, 2 H, 3J = 7.4,
2 CH). 13C NMR (125.7 MHz, CDCl3): d 22.3 (2 Me), 33.9 (CH2), 67.3 (CH2), 73.7 (CH), 80.4 (CH), 121.3 (2 CH), 126.8 (CH), 128.9 (2 CH),
149.0 (C), 163.5 (C). Anal. Calcd. for C17H17NO3S (315.36): C, 64.74, H, 5.43, N, 4.44. Found: C, 64.65, H, 5.38, N, 4.35. 4-Methyl-N-(5-
propyl-1,3-oxathiolan-2-ylidene)benzenamine (3d): Yellow powder, yield: 0.47 g (89%). IR (KBr) (nmax/cmÀ1): 1762, 1642, 1590, 1481, 1373
and 1118. 1H NMR (500 MHz, CDCl3): d 1.15 (d, 6 H, 3J = 6.5, 2 Me), 2.33 (s, 3 H, Me), 3.31–3.38 (m, 2 H, CH2), 3.59–3.73 (m, 3 H, 3 CH),
4.71–4.73 (m, 1 H, CH), 7.06 (d, 2 H, 3J = 7.8, 2 CH), 7.25 (d, 2 H, 3J = 7.6, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 21.9 (Me), 22.1 (2 Me),
33.4 (CH2), 67.2 (CH2), 72.7 (CH), 80.3 (CH), 121.1 (2 CH), 129.7 (2 CH), 133.6 (C), 146.5 (C), 163.3 (C). Anal. Calcd. for C10H11NOS
(193.26): C, 62.15, H, 5.74, N, 7.25. Found: C, 61.98, H, 5.62, N, 7.14. 4-Methoxy-N-(5-propyl-1,3-oxathiolan-2-ylidene)benzenamine (3e):
Pale yellow powder, yield: 0.34 g (87%). IR (KBr) (nmax/cmÀ1): 1762, 1642, 1590, 1481, 1373 and 1118. 1H NMR (500 MHz, CDCl3): d 1.52
(d, 3 H, 3J = 6.2, Me), 3.01–3.05 (m, 1 H, CH), 3.33–3.37 (m, 1 H, CH), 4.71–4.75 (m, 1 H, CH), 6.97 (d, 2 H, 3J = 7.3, 2 CH), 7.10 (t, 1 H,
3J = 7.2, CH), 7.30 (t, 2 H, 3J = 7.2, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 19.4 (Me), 37.1 (CH2), 78.7 (CH), 119.5 (2 CH), 125.2 (CH),
129.1 (2 CH), 137.1 (C), 149.1 (C), 151.1 (C), 163.6 (C). Anal. Calcd. for C11H13NOS (207.29): C, 63.74, H, 6.32, N, 6.76. Found: C, 63.67, H,

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F. Rostami-Charati et al. / Chinese Chemical Letters 22 (2011) 1143–1146
6.26, N, 6.67. N-(5-(Phenoxymethyl)-1,3-oxathiolan-2-ylidene)benzenamine (3f): Pale yellow powder, yield: 0.35 g (85%). IR (KBr) (nmax
/
cmÀ1): 1762, 1642, 1590, 1481, 1373 and 1118. 1H NMR (500 MHz, CDCl3): d 1.52 (d, 3 H, 3J = 6.2, Me), 2.29 (s, 3 H, Me), 3.03–3.08 (m, 1
H, CH), 3.36–3.39 (m, 1 H, CH), 4.73–4.76 (m, 1 H, CH), 7.22 (d, 2 H, 3J = 8.5, 2 CH), 7.27 (d, 2 H, 3J = 8.5, CH). 13C NMR (125.7 MHz,
CDCl3): d 19.5 (Me), 20.7 (Me), 37.8 (CH2), 78.5 (CH), 119.1 (2 CH), 129.6 (2 CH), 134.6 (C), 137.0 (C), 146.5 (C), 163.3 (C). Anal. Calcd. for
C
11H13NO2S (223.29): C, 59.17, H, 5.87, N, 6.27. Found: C, 59.25, H, 5.92, N, 6.34. 4-Methyl-N-(5-(phenoxymethyl)-1,3-oxathiolan-2-
ylidene)benzenamine (3g): Pale yellow powders, yield: 0.45 g (89%). IR (KBr) (nmax/cmÀ1): 2925, 1652, 1593, 1491, 1100, 912 and 744. 1H
NMR (500.1 MHz, CDCl3): d 1.22 (d, 6 H, 3J = 6.2, 2 Me), 3.34–3.42 (m, 2 H, CH2), 3.62–3.70 (m, 3 H, 3 CH), 4.76–4.77 (m, 1 H, CH), 6.98
(d, 2 H, 3J = 7.6, 2 CH), 7.12 (t, 1 H, 3J = 7.4, CH), 7.33 (t, 2 H, 3J = 7.4, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 22.3 (2 Me), 33.9 (CH2), 67.3
(CH2), 73.7 (CH), 80.4 (CH), 121.3 (2 CH), 126.8 (CH), 128.9 (2 CH), 149.0 (C), 163.5 (C). Anal. Calcd. for C13H17NO2S (251.34): C, 62.12,
H, 6.82, N, 5.57. Found: C, 61.97, H, 6.78, N, 5.48. 4-Methoxy-N-(5-(phenoxymethyl)-1,3-oxathiolan-2-ylidene)benzenamine (3h): Yellow
powders, yield: 0.47 g (89%). IR (KBr) (nmax/cmÀ1): 2925, 1692, 1543, 1491, 1100, 912 and 780. 1H NMR (500.1 MHz, CDCl3): d 1.15 (d, 6 H,
3J = 6.5, 2 Me), 2.33 (s, 3 H, Me), 3.31–3.38 (m, 2 H, CH2), 3.59–3.73 (m, 3 H, 3 CH), 4.71–4.73 (m, 1 H, CH), 7.06 (d, 2 H, 3J = 7.8, 2 CH),
7.25 (d, 2 H, 3J = 7.6, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 21.9 (Me), 22.1 (2 Me), 33.4 (CH2), 67.2 (CH2), 72.7 (CH), 80.3 (CH), 121.1 (2
CH), 129.7 (2 CH), 133.6 (C), 146.5 (C), 163.3 (C). Anal. Calcd. for C14H19NO2S (265.37): C, 63.37, H, 7.22, N, 5.28. Found: C, 63.32, H,
7.18, N, 5.20. N-(5-Isopropoxymethyl-1,3-oxathiolan-2-ylidene)benzenamine (3i): Pale yellow powders, yield: 0.49 g (87%). IR (KBr) (nmax
/
cmÀ1): 2925, 1692, 1543, 1491, 1100, 912 and 780. 1H NMR (500.1 MHz, CDCl3): d 1.17 (d, 6 H, 3J = 6.5, 2 Me), 3.32–3.40 (m, 2 H, CH2),
3.64–3.71 (m, 2 H, CH2), 3.72–3.75 (m, 1 H, CH), 3.78 (s, 3 H, MeO), 4.69–4.74 (m, 1 H, CH), 6.84 (d, 2 H, 3J = 8.8, 2 CH), 6.91 (d, 2 H,
3J = 8.8, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 22.0 (2 Me), 33.5 (CH2), 55.4 (MeO), 67.3 (CH2), 72.7 (CH), 80.2 (CH), 114.3 (2 CH), 122.3
(2 CH), 142.3 (C), 156.5 (C), 163.3 (C). Anal. Calcd. for C14H19NO3S (281.37): C, 59.76, H, 6.81, N, 4.98. Found: C, 59.65, H, 6.74, N, 4.87.
N-(5-Isopropoxymethyl-1,3-oxathiolan-2-ylidene)-4-methylbenzenamine (3j): Pale yellow powders, yield: 0.40 g (86%). IR (KBr) (nmax
/
cmÀ1): 1762, 1642, 1590, 1481, 1373 and 1118. 1H NMR (500.1 MHz, CDCl3): d 1.10 (t, 2 H, 3J = 7.4, Me), 1.77–1.82 (m, 2 H, CH2), 1.93–
1.99 (m, 2 H, CH2), 2.32 (s, 3 H, Me), 3.07–3.11 (m, 1 H, CH), 3.33–3.37 (m, 1 H, CH), 4.52–4.56 (m, 1 H, CH), 6.88 (d, 2 H, 3J = 8.2, 2 CH),
7.12 (d, 2 H, 3J = 8.2, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 10.9 (Me), 21.6 (CH2), 21.9 (Me), 27.8 (CH2), 36.8 (CH2), 84.5 (CH), 121.7 (2
CH), 129.4 (2 CH), 134.5 (C), 147.4 (C), 164.3 (C). Anal. Calcd. for C13H17NOS (235.34): C, 66.35, H, 7.28, N, 5.95. Found: C, 66.28, H, 7.19,
N, 5.87. N-(5-Isopropoxymethyl-1,3-oxathiolan-2-ylidene)-4-methoxybenzenamine (3k): Pale yellow powders, yield: 0.44 g (87%). IR (KBr)
(nmax/cmÀ1): 1762, 1642, 1590, 1481, 1373 and 1118. 1H NMR (500.1 MHz, CDCl3): d 1.10 (t, 2 H, 3J = 7.4, Me), 1.77–1.82 (m, 2 H, CH2),
1.93–1.99 (m, 2 H, CH2), 3.08–3.12 (m, 1 H, CH), 3.34–3.37 (m, 1 H, CH), 3.81 (s, 3 H, MeO), 4.52–4.55 (m, 1 H, CH), 6.85 (d, 2 H, 3J = 8.2, 2
CH), 6.92 (d, 2 H, 3J = 8.2, 2 CH). 13C NMR (125.7 MHz, CDCl3): d 10.8 (Me), 28.1 (CH2), 30.4 (CH2), 36.9 (CH2), 56.4 (MeO), 84.5 (CH),
115.2 (2 CH), 123.6 (2 CH), 143.3 (C), 157.3 (C), 164.3 (C). Anal. Calcd. for C13H17NO2S (251.34): C, 62.12, H, 6.82, N, 5.57. Found: C,
61.97, H, 6.73, N, 5.48.