4
4
V. March‡n et al.
SHORT PAPER
the concentration of dimethyldioxirane are important for sulfate triple salt or Oxoneª) to an acetone/aq NaHCO mixture.
3
The dimethyldioxirane/acetone solution was distilled at reduced
the quantitative transformation of the dithiolanone 1 into
the 1,1-dioxide 3, since a 95:5 mixture of 3 and 2 was ob-
tained when the reaction was carried out with a ~40 mM
solution of dimethyldioxirane. The preparation of 3H-1,2-
benzodithiol-3-one 1,1-dioxide might be scaled-up by
pressure (~150 Torr) and kept dry over MgSO at Ð20¡C. The di-
4
oxirane concentration (70Ð90 mM) was determined by addition to
an aliquot of aq KI and AcOH and titration of the iodine formed
with Na S O soln.
2
2
3
A solution of 3H-1,2-benzodithiol-3-one (1) (600 mg, 3.56 mmol)
in acetone (HPLC grade, 15 mL) was added, dropwise over 20 min
2
8
concentration of the dimethyldioxirane solutions.
In summary, treatment with one- or twofold molar excess- to 74 mM dimethyldioxirane in acetone (200 mL, 14.8 mmol) at r.t.
The mixture was magnetically stirred at r.t. and its progress was
monitored by TLC and GC. The conversion of 3H-1,2-benzodithi-
ol-3-one (1) into 3H-1,2-benzodithiol-3-one 1,1-dioxide (3) was
quantitative in 2Ð4 h, as checked by comparison with a commercial
es of dimethyldioxirane is a convenient alternative for ox-
idation to the 1-oxide, whereas larger excesses of reagent
allow the 1,1-dioxide to be obtained. This procedure, use-
ful for laboratory gram-scale preparations, allows quanti-
sample. The solvent was eliminated under reduced pressure, and the
tative oxidation to be achieved, whilst the large scale
product was dried by coevaporation with anhyd MeCN. The crude
oxidation of 3H-1,2-benzodithiol-3-one to the 1,1-dioxide product (slightly yellow, mp 96Ð97¡C) was dissolved in CH Cl2
2
2
0
with H O /trifluoroacetic acid has been reported to take and filtered, and solid 3 was obtained by the addition of hexanes.
2
2
Elimination of the solvent under reduced pressure afforded the tar-
place in 49% yield.
20
get product 3 as a white crystalline solid; mp 98.5Ð99.5¡C (lit. mp
1
02.5Ð103¡C, lit.21 mp 98Ð99¡C). TLC (CHCl ): R = 0.77.
3 f
3
H-1,2-Benzodithiol-3-one (1)
On completion of the reaction between 2-mecaptobenzoic acid (5 g,
2.4 mmol) and thiolacetic acid (4.7 mL, 65.7 mmol) in the pres-
ence of H SO (50 mL) (cf. ref 19), the dark crude mixture was
IR (CHCl
): n = 898, 1159, 1334, 1720 cmÐ1.
3
3
1
H NMR (CDCl , 300 MHz): d = 7.88 (t, 1H), 7.99 (t, 1H), 8.05 (d,
3
2
4
1H), 8.13 (d, 1H).
poured onto ice and the precipitate filtered and washed with water.
CHCl (70 mL) and sat. aq NaHCO (80 mL) were then added to the
1
3
C NMR (CDCl , 75 MHz): d = 121.8 (CH), 125.5 (CH), 130.0
3
3
3
(
Cq.), 134.3 (CH), 136.3 (CH), 148.4 (Cq), 182.9 (C=O).
crude solid. The mixture was stirred for 1 h at r.t., filtered and
washed with CHCl and NaHCO , and these filtrates were com-
3
3
EI-MS: m/z (%) = 69 (28), 76 (73), 96 (8), 104 (33), 108 (40), 136
(100), 200 (M) (29), 201 (M + 1) (3), 202 (M + 2) (39).
bined with the previous ones. No 3H-1,2-benzodithiol-3-one was
obtained from additional treatment of the solid with hot CHCl (re-
3
flux, 1.5 h). The organic and aqueous phases were separated and the
aqueous layer was washed with CHCl . The combined organic ex- Acknowledgement
3
tracts were washed with NaHCO and water, dried (MgSO ), fil-
3
4
This work was supported by funds from the DGICYT (grant PB94-
844) and the Generalitat de Catalunya (SRG96-1 and Centre de
Refer•ncia de Biotecnologia).
tered and treated with activated charcoal pellets. Crude 3H-1,2-
benzodithiol-3-one 1 was obtained as a crystalline dark yellow solid
after filtration and evaporation of the solvent; yield: 4.54 g (86%);
0
2
0
mp 73Ð74¡C (lit. mp 73Ð74¡C). The product was recrystallized
from EtOH (66% overall synthesis and purification yield); TLC
References
(
CHCl ): R = 0.63.
3 f
1
3
(1) Ratajczak, M. Z.; Gewirtz, A. M. In Nucleic Acids and Mol-
ecular Biology; Eckstein, F.; Lilley, D. M. J. Eds.; Springer-
Verlag: Berlin, 1994; Vol. 8; p 298.
C NMR (CDCl , 50 MHz): d = 125.2 (CH), 126.2 (CH), 127.8
3
(
CH), 129.6 (Cq), 134.0 (CH), 148.8 (Cq), 194.2 (CO).
EI-MS: m/z (%) = 69 (14), 76 (94), 96 (36), 104 (35), 140 (38), 168
M) (100), 169 (M + 1) (13), 170 (M + 2) (13).
(2) Zon, G.; Stec, W. J. In Oligonucleotides and Analogues. A
(
Practical Approach; Eckstein, F. Ed.; IRL Press: Oxford,
1
991; p 87.
Control of the Oxidation Reaction by Gas Chromatography
(3) Froehler, B. C. Tetrahedron Lett. 1986, 27, 5575.
(4) Agrawal, S.; Tang, J.-Y. Tetrahedron Lett. 1990, 31, 7541.
(5) Rao, M. V.; Macfarlane, K. Tetrahedron Lett. 1994, 35, 6741.
(6) Wyrzykiewicz, T. K.; Ravikumar, V. T. Bioorg. Med. Chem.
Lett. 1994, 4, 1519.
(7) Efimov, V.; Kalinkina, A. L.; Chakhmakhcheva, O. G.; Hill,
T. S.; Jayaraman, K. Nucleic Acids Res. 1995, 23, 4029.
(8) Xu, Q.; Musier-Forsyth, K.; Hammer, R. P.; Barany, G.
Nucleic Acids Res. 1996, 24, 1602.
GC conditions (HewlettÐPackard 5890A): Tracer TRB-5 column
(30 m), 7¡C/min gradient from 100¡C to 250¡C, injector tempera-
ture: 280¡C, detector temperature: 300¡C; t : 3H-1,2-benzodithiol-
R
3
3
-one (1) 9.0 min, 3H-1,2-benzodithiol-3-one 1-oxide (2) 11.6 min,
H-1,2-benzodithiol-3-one 1,1-dioxide (3) 11.4 min. 3 partially de-
composes under the analysis conditions, the area of main peak
amounting ~88% of the total area (authentic sample of commercial
origin).
(9) Xu, Q.; Barany, G.; Hammer, R. P.; Musier-Forsyth, K. Nu-
3
H-1,2-Benzodithiol-3-one 1-Oxide (2)
cleic Acids Res. 1996, 24, 3643.
This was the main product when the oxidation of 1 was attempted
with one- or twofold molar excess of dimethyldioxirane; TLC
(10) Cheruvallath, Z. S.; Cole, D. L.; Ravikumar, V. T. Nucleosi-
des Nucleotides 1996, 15, 1441.
(11) Gerster, M.; Maier, M.; Clausen, N.; Schewitz, J.; Bayer, E.
(
CHCl ): R = 0.54.
3
f
Z. Naturforsch. 1997, 52b, 110.
1
3
C NMR (CDCl , 50 MHz): d = 126.9 (CH), 128.0 (CH), 131.1
3
(
12) Ma, M. Y-X.; Dignam, J. C.; Fong, G. W.; Li, L.; Gray, S. H.;
Jacob-Samuel, B.; George, S. T. Nucleic Acids Res. 1997, 25,
3590.
(
Cq), 133.1 (CH), 135.6 (CH), 151.9 (Cq), 190.2 (CO).
GC-EI-MS: m/z (%) = 69 (33), 76 (61), 96 (20), 104 (22), 136 (100),
1
84 (M) (21), 185 (M + 1) (2), 186 (M + 2) (2).
(13) Kamer, P. C. J.; Roelen, H. C. P. F.; van den Elst, H.; van der
Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1989, 30,
6757.
3
H-1,2-Benzodithiol-3-one 1,1-Dioxide (3)
Dimethyldioxirane was prepared following described proce-
(14) Iyer, R. P.; Egan, W.; Regan, J. B.; Beaucage, S. L. J. Am.
Chem. Soc. 1990, 112, 1253.
2
9,30
dures,
by addition of potassium peroxymonosulfate (monoper-
Synthesis 1999, No. 1, 43Ð45 ISSN 0039-7881 © Thieme Stuttgart · New York