A simple and efficient direct method for the synthesis of symmetric dibenzyl sulfones from sodium dithionite and benzyl chlorides in ionic liquid

Article abstract of DOI:10.1007/s00706-006-0530-0

Symmetric dibenzyl sulfones were synthesized in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF₄) at 100°C from various benzyl chlorides and sodium dithionite in moderate yields.

Full text of DOI:10.1007/s00706-006-0530-0

Monatshefte f€ur Chemie 137, 1315–1319 (2006)
DOI 10.1007/s00706-006-0530-0
A Simple and Efficient Direct Method
for the Synthesis of Symmetric Dibenzyl
Sulfones from Sodium Dithionite and Benzyl
Chlorides in Ionic Liquid
ꢀ
Yi-Qun Li and Li-Ping Zhang
Department of Chemistry, Jinan University, Guangzhou, China
Received January 23, 2006; accepted March 6, 2006
Published online September 15, 2006 # Springer-Verlag 2006
Summary. Symmetric dibenzyl sulfones were synthesized in ionic liquid 1-butyl-3-methylimidazo-
lium tetrafluoroborate ([bmim]BF4) at 100ꢁC from various benzyl chlorides and sodium dithionite in
moderate yields.
Keywords. Dibenzyl sulfones; Sodium dithionite; Benzyl chloride; Ionic liquid; Synthesis.
Introduction
The use of sulfones in organic synthesis has become increasing important in recent
years [1]. From the methodological point of view, sulfones have been employed
in the preparation and functionalization of a wide variety of products by stabilizing
ꢀ-radicals [2], ꢀ-anions [3], and acting as cationic synthons [4]. Sulfones are also
widely used in medicinal chemistry and found on numerous drugs, including the
recently developed selective COX-2 inhibitor Vioxx [5].
The most common and straightforward procedure for the preparation of sulfones
is the oxidation of the corresponding sulfides and sulfoxides [6]. Other methods may
include the alkylation of sulfinate salts [7], Friedel-Crafts type reaction of sulfonyl
chlorides [8], and coupling reaction of aryl halides and sulfinic acid salts [9]. But
these protocols often suffer from drawbacks such as side reactions, limited substrate
sources, toxic solvents, irritant and foul smell, low yields, and so on, and thus reduce
their scope of application. More recently, the metal mediated cross coupling reac-
tions of sulfinate salts with halides and triflates were reported as mild alternatives to
these previous methods. Among these synthetic strategies, only a few direct syn-
thetic methods were observed for preparation of symmetric dibenzyl sulfones.
ꢀ
Corresponding author. E-mail: tlyq@jnu.edu.cn

1316
Y.-Q. Li and L.-P. Zhang
In 1964, Wellisch et al. [10] reported a one step synthesis of dibenzyl sulfones
by the reaction of sodium dithionite with benzyl chloride in DMF at 110ꢁC for 9 h
with a yield of 17%. Then, Amiri et al. [11] in 1978 also prepared the di-ꢀ-methyl-
enenaphthyl sulfone with the similar method in DMSO at 110ꢁC for 9 h with a
yield of 18%. However, these procedures have suffered from disadvantages such as
limited number of substrates, low yield, and long reaction time. Therefore, further
improvements to synthesize these sulfones would be desirable.
The development of environmentally friendly solvents for organic chemistry is
an area of considerable importance. From both economical and environmental
points of view, the use of ionic liquids as solvents has attracted much interesting
recently, partly due to their polar nature, their phase behavior, and their lack of
vapour pressure.
Based on our previous works at ionic liquids and inspired by relative studies
reported in literature, we have explored the direct synthesis of symmetric dibenzyl
sulfones from sodium dithionite and benzyl chlorides in ionic liquid 1-butyl-3-
methylimmidazolium tetrafluoroborate ([bmim]BF4).
Results and Discussion
The general process is shown in Scheme 1 in which sodium dithionite reacts with a
series of benzyl chlorides to produce corresponding symmetric dibenzyl sulfones.
Scheme 1
Table 1. Synthesis of symmetric dibenzyl sulfones from sodium dithionite and benzyl chlorides
Entry
Benzyl chloride
Producta
Time=h
Yieldb=%
a
b
c
d
e
f
C6H5CH2Cl
(C6H5CH2)2SO2
4
6
6
6
6
6
6
6
6
6
5
78 (76)c
70
2-FC6H4CH2Cl
3-FC6H4CH2Cl
4-FC6H4CH2Cl
2-ClC6H4CH2Cl
3-ClC6H4CH2Cl
4-ClC6H4CH2Cl
2-MeC6H4CH2Cl
3-MeC6H4CH2Cl
4-MeC6H4CH2Cl
(2-FC6H4CH2)2SO2
(3-FC6H4CH2)2SO2
(4-FC6H4CH2)2SO2
(2-ClC6H4CH2)2SO2
(3-ClC6H4CH2)2SO2
(4-ClC6H4CH2)2SO2
(2-MeC6H4CH2)2SO2
(3-MeC6H4CH2)2SO2
(4-MeC6H4CH2)2SO2
53
78
57
50
g
h
i
57
66
73
j
77
k
75
a
1
Products were characterized by their IR spectra, H NMR, mass spectra, and elemental analysis;
isolated yields based on benzyl chloride; c yield in parenthesis is based on the recovered ionic liquid
b

Synthesis of Symmetric Dibenzyl Sulfones
1317
Sodium dithionite when treated with various benzyl chlorides in ionic liquid
[bmim]BF4 affords sulfones in moderate to good yields. In most cases, the reaction
was completed in about 4–6 h at 100ꢁC. The results are shown in Table 1.
Compared with the two previous results in DMF [10] and DMSO [11], our ionic
liquid system was superior to them in many aspects such as rate and yield.
To explore the scope of this reaction, we extended the reaction of sodium
dithionite with various benzyl chlorides carrying either electron withdrawing
or electron releasing constituents in aromatic cycles. Benzyl chlorides bearing
either an electron withdrawing or an electron donating group in the ortho-
position of the aromatic ring give lower yields owing to their higher steric
hindrance (Table 1, entries b, e, and h). When the electron withdrawing group
was at the meta-position on the aromatic ring of the benzyl chloride, the yield
of sulfone was slightly poorer than when the same group was at another posi-
tion (Table 1, entries c and f). When there was a chloride on the aromatic cycle
of the benzyl chloride, they worked less efficient to form sulfones than with
other substituents.
Another merit of the ionic liquid is that it is recyclable as reaction medium. In
view of environmentally friendly methodologies, recovery and reuse of the ionic
liquid is highly preferable. [bmim]BF4 is easily separated from the water media
after the quench of the reaction and it can be recovered and reused for a next run
without loss of efficiency after removal of the organic extractant.
In conclusion, we have devised a simple and efficient direct one pot synthesis of
symmetric dibenzyl sulfones. This protocol is featured by easy availability of
starting materials, mild conditions, simple manipulation, ease of isolation of the
products, and it is benign to the environment.
Experimental
Melting points were measured on an Electrothemal X6 microscopy digital melting point apparatus and
are uncorrected. IR spectra were recorded on a Bruke Equinox-55 spectrometer using KBr pellets. 1H
NMR spectra were recorded in CDCl3 on a Bruker AVANCE 300 (300 MHz) instrument with TMS at
ꢁ ¼ 0.00 ppm or the residual CHCl3 at ꢁ ¼ 7.24ppm as an internal standard. Mass spectra were
performed on a QP5050A GC-MS. Elemental analyses were obtained from a Vario EL elemental
analyzer; results agreed favorably with calculated values. Chemicals used were of commercial grade
without further purification.
General Procedure for the Synthesis of Symmetric Dibenzyl Sulfones 3a–3k
A mixture of benzyl chloride (5mmol), sodium dithionite (3mmol), and ionic liquid [bmim]BF4
(3cm3) was stirred at 100ꢁC for about 4–6 h. The progress of the reaction was monitored by TLC.
After completion of the reaction, the mixture was poured into distilled water (10 cm3). The precipitated
solid was filtered off and washed with water. The crude products were purified by recrystallization with
ethanol water mixtures. The ionic liquid was recovered by extracting the water phase with dichloro-
methane and was used in subsequent runs after removing the dichloromethane.
Dibenzyl sulfone (3a, C14H14SO2)
Yield 78%; mp 150–152ꢁC; 1H NMR (300 MHz, CDCl3): ꢁ ¼ 7.35–7.41 (m, 10H), 4.11 (s, 4H) ppm;
IR (KBr): ꢂꢀ¼ 3103, 3062, 3034, 2985, 2937, 2856, 1637, 1605, 1545, 1495, 1453, 1409, 1297, 1120,
817, 765, 722, 619, 539 cmꢂ1; MS (70 eV): m=z ¼ 246 (Mþ, 1), 182 (10), 91 (100).

1318
Y.-Q. Li and L.-P. Zhang
Di(2-flourobenzyl) sulfone (3b, C14H12F2SO2)
1
Yield 75%; mp 160–162ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.42–7.53 (m, 2H, Ar–H), 7.40–7.42
(m, 2H, Ar–H), 7.13–7.24 (m, 4H, Ar–H), 4.33 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3083, 3007, 2952,
1620, 1586, 1495, 1456, 1418, 1309, 1236, 1193, 1134, 1091, 905, 853, 769, 703, 657, 618cmꢂ1; MS
(70 eV): m=z ¼ 282 (Mþ, 1), 218 (36), 109 (100).
Di(3-flourobenzyl) sulfone (3c, C14H12F2SO2)
1
Yield 53%; mp 152–154ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.39–7.44 (m, 2H, Ar–H), 7.11–7.17
(m, 6H, Ar–H), 4.16 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3065, 2983, 2933, 1589, 1486, 1448, 1416,
1308, 1271, 1237, 1150, 1123, 1078, 948, 898, 797, 760, 689, 636 cmꢂ1; MS (70 eV): m=z ¼ 282
(Mþ, 3), 218 (27), 109 (100).
Di(4-flourobenzyl) sulfone (3d, C14H12F2SO2)
1
Yield 78%; mp 190–191ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.35–7.40 (m, 4H, Ar–H), 7.09–7.15
(m, 4H, Ar–H), 4.13 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3052, 2980, 2935, 1607, 1511, 1418, 1311, 1287,
1240, 1161, 1130, 842, 787, 751, 563, 531 cmꢂ1; MS (70 eV): m=z ¼ 282 (Mþ, 1), 218 (19), 109 (100).
Di(2-chlorobenzyl) sulfone (3e, C14H12Cl2SO2)
1
Yield 57%; mp 189–191ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.55–7.58 (m, 2H, Ar–H), 7.46–7.49
(m, 2H, Ar–H), 7.32–7.37 (m, 4H, Ar–H), 4.51 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3081, 3002, 2959,
1638, 1575, 1475, 1440, 1413, 1317, 1285, 1125, 1046, 823, 776, 739, 677, 616, 523, 485cmꢂ1; MS
(70 eV): m=z ¼ 314 (Mþ, 0.5), 250 (6), 127 (31), 125 (100).
Di(3-chlorobenzyl) sulfone (3f, C14H12Cl2SO2)
1
Yield 50%; mp 197–198ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.38–7.42 (m, 6H, Ar–H), 7.27–7.30
(m, 2H, Ar–H), 4.13 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3076, 2996, 2946, 1594, 1577, 1477, 1312,
1276, 1123, 1088, 909, 863, 805, 742, 685, 633, 533, 482 cmꢂ1; MS (70 eV): m=z ¼ 314 (Mþ, 2), 250
(11), 127 (64), 125 (100).
Di(4-chlorobenzyl) sulfone (3g, C14H12Cl2SO2)
1
Yield 57%; mp 249–250ꢁC; H NMR (300MHz, CDCl3): ꢁ ¼ 7.22 (d, 4H, J ¼ 2 Hz, Ar–H), 7.42 (d,
4H, J ¼ 2 Hz, Ar–H), 4.11 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3064, 2991, 2942, 2853, 1642, 1597,
1490, 1453, 1411, 1306, 1274, 1118, 1018, 816, 739, 642, 583, 510cmꢂ1; MS (70 eV): m=z ¼ 314
(Mþ, 1), 250 (10), 127 (64), 125 (100).
Di(2-methylbenzyl) sulfone (3h, C16H18SO2)
Yield 66%; mp 169–171ꢁC; 1H NMR (300MHz, CDCl3): ꢁ ¼ 7.36–7.39 (m, 2H, Ar–H), 7.24–7.31(m,
6H, Ar–H), 4.32 (s, 4H, 2CH2), 2.38 (s, 6H, 2CH3) ppm; IR (KBr): ꢂꢀ¼ 3060, 3023, 2953, 2919, 2865,
1494, 1457, 1417, 1314, 1287, 1120, 792, 754, 620, 597, 570, 516, 482 cmꢂ1; MS (70 eV): m=z ¼ 274
(Mþ, 0.5), 210 (10), 105 (100).
Di(3-methylbenzyl) sulfone (3i, C16H18SO2)
1
Yield 73%; mp 116–118ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.30–7.35 (m, 2H, Ar–H), 7.20–7.25
(m, 6H, Ar–H), 4.13 (s, 4H, 2CH2), 2.40 (s, 6H, 2CH3) ppm; IR (KBr): ꢂꢀ¼ 3060, 3023, 2953, 2919,
2865, 1494, 1457, 1417, 1314, 1287, 1120, 792, 754, 620, 597, 570, 516, 482 cmꢂ1; MS (70 eV):
m=z ¼ 274 (Mþ, 2), 210 (11), 105 (100).
Di(4-methylbenzyl) sulfone (3j, C16H18SO2)
1
Yield 77%; mp 204–206ꢁC; H NMR (300MHz, CDCl3): ꢁ ¼ 7.29 (d, J ¼ 8.10 Hz, 4H, Ar–H), 7.22
(d, J ¼ 8.14 Hz, 4H, Ar–H), 4.10 (s, 4H, 2CH2), 2.39 (s, 6H, 2CH3) ppm; IR (KBr): ꢂꢀ¼ 3031, 2973,

Synthesis of Symmetric Dibenzyl Sulfones
1319
2925, 2863, 1647, 1613, 1514, 1449, 1416, 1307, 1283, 1118, 1036, 818, 766, 697, 603, 517 cmꢂ1; MS
(70 eV): m=z ¼ 274 (Mþ, 1), 210 (8.5), 105 (100).
Di(2-methylenenaphthyl) sulfone (3k, C22H18SO2)
1
Yield 75%; mp 218–219ꢁC; H NMR (300 MHz, CDCl3): ꢁ ¼ 7.89–8.00 (m, 6H, Ar–H), 7.44–7.61
(m, 8H, Ar–H), 4.76 (s, 4H, 2CH2) ppm; IR (KBr): ꢂꢀ¼ 3047, 3006, 2952, 2856, 1637, 1596, 1512,
1419, 1301, 1215, 1119, 1016, 778, 739, 553, 508, 479 cmꢂ1; MS (70 eV): m=z ¼ 346 (Mþ, 3), 282
(6.7), 141 (100).
Acknowledgements
We are grateful to the National Natural Science Foundation of China (20272018) and the Guangdong
Natural Science Foundation (04010458, 021166) for financial support.
References
[1] a) Patai S, Rappoport Z, Stirling C (1988) The Chemistry of Sulphones and Sulfoxides. John
Wiley & Sons, Chichester; b) Simpkins NS (1993) Sulphones in Organic Synthesis. Pergamon
Press, Oxford; c) Langcake P, Pryce RJ (1976) Physiol Plant Pathol 9: 77
[2] Paquette LA (2001) Synlett 1
´
[3] Najera C, Sansano JM (1998) Recent Res Devel Org Chem 2: 637
´
[4] Chinchilla R, Najera C (1997) Recent Res Devel Org Chem 1: 437
[5] Prasit P, Wang Z, Brideau C, Chan CC, Charleston S, Cromlish W, Wthier D, Evans JF,
Ford-Hutchinson AW, Gauthier JY, Gordon R, Guay J, Gresser M, Kargman S, Kennedy B,
ꢁ
Leblance Y, Leger S, Mancini J, O’Neill GP, Ouellet M, Percival MD, Perrier H, Riendeau D,
Rodger I, Tagari P, Therien M, Vickers P, Wong E, Xu LJ, Young RN, Zamboni R (1999) Bioorg
ꢁ
Med Chem Lett 9: 1773
ꢁ
[6] a) Hudlicky M (1999) Oxidation in Organic Chemistry; ACS Monograph Ser. 186. American
Chemical Society: Washington, DC, pp 250–264; b) Alonso DA, Najera C, Varea M (2002)
´
Tetrahedron Lett 43: 3459; c) Sato K, Hyodo M, Aoki M, Zhang XQ, Noyori R (2001)
Tetrahedron 57: 2469
[7] a) Magnus PD (1977) Tetrahedron 33: 2019; b) Procter DJ (1999) J Chem Soc Perkin Trans 1, 641
[8] a) Garzya V, Forbes IT, Lauru S, Maragni P (2004) Tetrahedron Lett 45: 1499; b) Alexander MV,
ꢁ
Khandekar AC, Samant SD (2004) J Mol Catal A Chem 223: 75; c) Marquie J, Laporterie A,
Dubac J, Roques N, Desmurs JR (2001) J Org Chem 66: 421; d) Repichet S, Le Roux C,
ꢁ
Hernandez P, Dubac J, Desmus JR (1999) J Org Chem 64: 6479
[9] a) Zhu W, Ma D (2005) J Org Chem 70: 2696; b) Cacchi S, Fabrizi G, Goggiamani A, Parisi LM,
Bernini R (2004) J Org Chem 69: 5608; c) Suzuki H, Abe H (1995) Tetrahedron Lett 36: 6239
[10] Wellisch E, Gipstein E, Sweeting OJ (1964) Polym Lett B2, 35
[11] Amiri A, Mellor JM (1978) J Photochem 9: 571