Benzothiazol-2-yl(difluoro)methanesulfonic acid: Synthesis and reactions

Article abstract of DOI:10.1134/S1070428006080148

The condensation of o-aminothiophenol with sulfodifluoroacetic acid led to the formation of benzothiazol-2-yl(difluoro)methanesulfonic acid whose aryldiazonium salts were converted by pyrolysis into aryl benzothiazol-2- yl(difluoro)methanesulfonates. Nauka/Interperiodica 2006.

Full text of DOI:10.1134/S1070428006080148

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 8, pp. 1188-1191. Ó Pleiades Publishing, Inc. 2006.
Original Russian Text Ó V.P. Nazaretyan, N.D. Volkov, N.I. Liptuga, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 8,
pp. 1208-1211.
Benzothiazol-2-yl(difluoro)methanesulfonicAcid: Synthesis
and Reactions
V.P. Nazaretyan, N.D. Volkov, and N.I. Liptuga
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, 02094 Ukraine
e-mail: volkov_nd@ukr.net
Received September 2005
Abstract—The condensation of o-aminothiophenol with sulfodifluoroacetic acid led to the formation of
benzothiazol-2-yl(difluoro)methanesulfonic acid whose aryldiazonium salts were converted by pyrolysis into aryl
benzothiazol-2-yl(difluoro)methanesulfonates.
DOI: 10.1134/S1070428006080148
We formerly prepared benzothiazol-2-yl(difluoro)-
methanesulfonyl fluoride, an analog of trifluoromethane-
sulfonyl fluoride containing a benzothiazolyl group instead
of one fluorine atom. The preparation method consisted
in reacting cyanodifluoromethanesulfonyl fluoride with
methanesulfonic acid is a fluid.Apparently benzothiazol-
2-yl(difluoro)methanesulfonic acid (IIa) exist in the form
of an internal salt IIb.
6
&
) 62 2+
2-aminothiophenol to give the benzothiazol-2-yl(difluoro)-
1
methanesulfonyl fluoride in a 32% yield [1]. The alkaline
hydrolysis of the sulfonyl fluoride followed by acidifying
resulted in the preparation of benzothiazol-2-yl(difluoro)-
methanesulfonic acid in an overall yield not exceeding
,,D
6
&
) 62 2
2
2%.
The goal of the present study was a development of
a preparative procedure for the synthesis of benzothiazol-
-yl(difluoro)methanesulfonic acid and investigation of its
properties.
We found that in the condensation of the available
sulfodifluoroacetic acid [2] with the 2-aminothiophenol
I) formed acid II in a 70% yield notwithstanding the
relatively rigid reaction conditions.
1
+
,
,E
2
Sulfonic acid IIa formed with various cations salts
soluble in water. In the synthesis of salts III–VI we used
the alkali metals hydroxides, and the zinc salt VII was
prepared form the zinc oxide.
(
6
0
ꢀꢀ2+
,,D
6+
&) 62 2 0
,,, 9,
M = NH , Li, Na, K.
ꢀꢁ+2&2&) 62 2+
1
1+
,
4
6
ꢂꢃꢃ &
We attempted to synthesize acid IIa chloride to be
used in preparation of the acid derivatives. However it
turned out that neither sulfonic acid IIa nor its sodium
salt V reacted with the phosphorus pentachloride. We
also failed to obtain the corresponding sulfonyl chloride
treating acid IIa with the phosphorus pentachloride in
&
) 62 2+ꢁꢀꢁ+ 2
1
,,D
Sulfonic acid IIa is a high-melting colorless crystalline
compound whereas its closest analog, the trifluoro-
1188

BENZOTHIAZOL-2-YL(DIFLUORO)METHANESULFONIC ACID
1189
the presence of zinc chloride. Instead of benzothiazol-2-
yl(difluoro)methanesulfonyl chloride (VIIIa) we isolated
to compare it with the closest analog, the trifluoro-
methanesulfonyloxy group. To this end we prepared
m-fluoro- and p-fluorophenyl trifluoromethanesulfonates
XIIIa and XIIIb by decomposition of the m-fluoro- and
p-fluorophenyldiazonium trifluoromethanesulfonates XIIa
and XIIb.
2-(difluorochloromethyl)benzothiazole (VIIIb) originating
obviously from the decomposition of chloride VIIIa under
the reaction conditions.
3&O ꢀ=Q&O
6
Chemical shifts d were measured in the 19F NMR
F
,,D
&
) 62 &O
spectra of benzothiazol-2-yl(difluoro)methanesulfonyloxy
and trifluoromethanesulfonyloxy groups, and also of the
fluorine atoms in the m-fluoro- and p-fluorophenyl esters
of the corresponding sulfonic acids. These data were
used in the calculation of the s-constants of substituted
difluoromethanesulfonyloxy groups containing as a sub-
stituent either fluorine atom or a benzothiazolyl moiety.
1
9
,,,D
) &Oꢁꢂꢁ62
,,,E
6
&
1
9
Benzothiazol-2-yl(difluoro)methanesulfonic acid (IIa)
with water solutions of aryldiazonium chlorides gave rise
to salts IXa and IXb which eliminated nitrogen on pyrolysis
to give aryl esters Xa and Xb.
The calculation of the s and s constants was
I
R
performed by formulas from [3], and the s and s
m
p
constants, by formulas from [4] (see the table).
As seen from the table, the benzothiazol-2-yl(difluoro)-
methanesulfonyloxy group is similar in the values of the
s and s substituents to the trifluoromethanesulfonyloxy
6
$U1 ꢀ&O
I
R
,,
&) 62 2 1 $U
;Dꢁꢀ,;E
group, with a little less inductive effect than that of the
latter. This result is in agreement with the smaller value
1
,
of the s of the benzothiazolyl moiety as compared with
I
6
ꢁ
ꢂ &
that of the fluorine atom (0.37 and 0.44 respectively [3]).
Both benzothiazol-2-yl(difluoro)methanesulfonyloxy and
trifluoromethanesulfonyloxy groups are p-donors.
&
) 62 2$U
1
1
;
Dꢁꢀ;E
Therewith the values of s constants of benzothiazol-2-
R
Ar = 3-FC H (a), Ar = 4-FC H (b).
6
4
6 4
yl-(difluoro)methanesulfonyloxy group and trifluoro-
methanesulfonyloxy group according to the calculations
based on our experimental data equal –0.19 and –0.17
The reaction of acid IIa with aryldiazonium chlorides
followed by decomposition of the diazonium salts can be
a convenient preparation method for aryl benzothiazol-2-
yl(difluoro)methanesulfonates.
respectively. The close s and s values for trifluoro-
I
R
methanesulfonyloxy group were reported before [5].
We tried to estimate the electronic character of the
benzothiazol-2-yl(difluoro)methanesulfonyloxy group and
EXPERIMENTAL
1H and 19F NMR spectra were registered on
a spectrometer VXR-300 at operating frequency 299.9
and 282.2 MHz respectively, internal references TMS
and CCl F, solvent DMSO-d (compounds II–VII),
1+ ꢀꢀ262 &)
3
6
)
ꢁ
PꢀꢁSꢂ
;,Dꢀꢁ;,E
CDCl (compounds VIIIb, Xa, Xb, XIIIa, and XIIIb).
3
s-Constants of substituted difluoromethanesulfonyloxy groups
1
ꢀꢀ262 &)
%X212
RCF SO O
2
2
)
ꢁ
PꢀꢁSꢂ
;,,Dꢀꢁ;,,E
2
62 &)
ꢃꢄ &
1
)
ꢁ
PꢀꢁSꢂ
;,,,Dꢀꢁ;,,,E
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 8 2006

1190
NAZARETYAN et al.
Commercial o-aminothiophenol (I) was used, sulfodi-
C H F KNO S . Calculated, %: C 31.68; H 1.33; N 4.62;
8 4 2 3 2
fluoroacetic acid was synthesized by procedure [2].
S 21.14.
Benzothiazol-2-yl(difluoro)methanesulfonic acid
IIa).Amixture of 1.25 g (10 mmol) of o-aminothiophenol
I) and 1.93 g (11 mmol) of sulfodifluoroacetic acid was
Zinc benzothiazol-2-yl(difluoro)methanesulfonate
(VII). Into a solution of 3 g (11.3 mmol) of acid II in
20 ml of water was added 1.5 g (18.5 mmol) of zinc
oxide, and the suspension was stirred for 2 h at room
temperature. Excess of the zinc oxide was filtered off,
the filtrate was evaporated on a water bath, and the
crystalline mass obtained was ground and dried in
a vacuum (20 mm Hg) at 100°C. Yield 3.0 g (92%),
(
(
within 1 h gradually heated to 200°C under reduced
pressure (20 mm Hg), and the heating at this temperature
was continued for 3 h more. On cooling activated carbon
and 10 ml of acetonitrile was added to the reaction
mixture. The mixture was boiled, then filtered, and the
mother liquor was evaporated. Yield 1.86 g (70%),
1
t.decomp. 355°C. H NMR spectrum, d, ppm: 7.58 m
1
(2Harom), 8.11 d (1Harom, J7.9 Hz), 8.15 d (1Harom, J7.5 Hz).
colorless crystals, mp 255–257°C. H NMR spectrum,
1
9F NMR spectrum, d, ppm: –101.0 s. Found, %: C 32.45;
d, ppm: 7.58 m (2H ), 8.13 d (1Harom, J 8.1 Hz), 8.19 d
arom
H 1.33; N 4.73; S 21.71. C H F N O S Zn. Calculated,
1
9
16
8
4
2
6 4
(
1Harom, J 7.6 Hz ). F NMR spectrum, d, ppm: –99.1 s.
%
: C 32.36; H 1.36; N 4.72; S 21.60.
-(Difluorochloromethyl)benzothiazole (VIIIa).
A mixture of 3.13 g (10.9 mmol) of sodium salt V, 6.9 g
33.2 mmol) of a fine powder of PCl , and 2.0 g of ZnCl
Found, %: C 36.09; H 1.79; N 5.21; S 24.26.
C H F NO S . Calculated, %: C 36.22; H 1.90; N 5.28;
2
8
5
2
3 2
S 24.17.
(
5
2
Ammonium benzothiazol-2-yl(difluoro)methane-
sulfonate (III). In 8 ml of 25% aqueous ammonia was
dissolved 2.65 g (10 mmol) of acid IIa, the solution was
evaporated on a water bath, the residue was ground and
dried in a vacuum (20 mm Hg) at 100°C.Yield quantitative,
was heated for 2 h at 180°C. The volatile products were
distilled off in a vacuum (20 mm Hg), 15 ml of dichloro-
methane were added to the residue, the mixture was
filtered, and the filtrate was washed with 8 ml of ice
water. The organic layer was separated and dried over
1
t.decomp. 282°C. H NMR spectrum, d, ppm: 7.58 m
CaCl , the solvent was removed. Yield 1.34 g (56%),
2
(
2Harom), 8.16 d (1Harom, J 8.5 Hz), 8.20 d (1Harom,
1
colorless oily substance. H NMR spectrum, d, ppm:
.57 m (2Harom), 7.96 d (1Harom, J 7.9 Hz), 8.19 d (1Harom,
J 7.5 Hz). F NMR spectrum, d, ppm: –47.95 s (publ.: –
7.5 ppm [6]). Found, %: C 43.66; H 1.71; Cl 16.31;
N 6.45; S 14.51. C H ClF NS. Calculated, %: C 43.75;
1
9
J 7.5 Hz). F NMR spectrum, d, ppm: –97.8 s. Found,
7
%
: C 34.22; H 2.84; N 9.86; S 22.84. C H F N O S .
8
8
2
2
3
2
19
Calculated, %: C 34.04; H 2.86; N 9.92; S 22.72.
4
Lithium, sodium, and potassium salts were obtained
similarly from the corresponding hydroxides in quantitative
yields.
8
4
2
H 1.84; Cl 16.14; N 6.38; S 14.60.
Aryldiazonium benzothiazol-2-yl(difluoro)-
methanesulfonates IXa and IXb. To a solution of
aryldiazonium chloride prepared from 4.7 mmol of
arylamine in 4 ml of 10% hydrochloric acid and 4.7 mmol
of sodium nitrite was added 2.6 mmol of a solution of
sulfonic acid II in 8 ml of water at 0–5°C, and the mixture
was stirred for 15–20 min with a glass rod; the separated
solidified precipitate was isolated and washed with ice
water (2´1 ml) and dried in a vacuum desiccator for 24 h
over phosphorus pentoxide with intermittent grinding.
Lithium benzothiazol-2-yl(difluoro)methane-
1
sulfonate (IV). T.decomp. 244°C. H NMR spectrum,
d, ppm: 7.58 m (2H ), 8.14 d (1Harom, J 8.1 Hz), 8.20 d
arom
1
9
(
1Harom, J 7.7 Hz). F NMR spectrum, d, ppm: –97.8 s.
Found, %: C 35.31; H 1.53; N 5.21; S 23.73.
C H F LiNO S . Calculated, %: C 35.43; H 1.49; N 5.16;
8
4
2
3 2
S 23.65.
Sodium benzothiazol-2-yl(difluoro)methane-
1
sulfonate (V). T.decomp. 259°C. H NMR spectrum,
d, ppm: 7.58 m (2H ), 8.14 d (1Harom, J 7.7 Hz), 8.20 d
3-Fluorophenyldiazonium benzothiazol-2-
yl(difluoro)methanesulfonate (IXa). Yield 86%,
t.decomp. 95°C. Found, %: C 43.31; H 2.00; N 10.93; S
16.43. C H F N O S . Calculated, %: C 43.41; H 2.08;
arom
1
9
(
1Harom, J 7.2 Hz). F NMR spectrum, d, ppm: –97.7 s.
Found, %: C 33.60; H 1.35; N 4.78; S 22.24.
C H F NNaO S . Calculated, %: C 33.45; H 1.40; N
8
4
2
3
2
14
8
3
3
3 2
4.87; S 22.32.
N 10.85; S 16.56.
Potassium benzothiazol-2-yl(difluoro)methane-
sulfonate (VI). T.decomp. 246°C. H NMR spectrum,
4-Fluorophenyldiazonium benzothiazol-2-
yl(difluoro)methanesulfonate (IXb). Yield 64%,
t.decomp. 96°C. Found, %: C 43.60; H 2.04; N 10.97;
S 16.47. C H F N O S . Calculated, %: C 43.41; H 2.08;
1
d, ppm: 7.58 m (2H ), 8.14 d (1Harom, J 7.0 Hz), 8.19 d
arom
1
9
(
1Harom, J 6.9 Hz). F NMR spectrum, d, ppm: –97.7 s.
14
8
3
3
3 2
Found, %: C 31.81; H 1.41; N 4.67; S 21.06.
N 10.85; S 16.56.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 8 2006

BENZOTHIAZOL-2-YL(DIFLUORO)METHANESULFONIC ACID
1191
O-Aryl benzothiazol-2-yl(difluoro)methane-
sulfonates Xa and Xb. Into a test tube placed into an oil
bath heated to 130–135°C was charged by small portions
dry finely ground aryldiazonium sulfonate IXa or IXb.
The heating continued for 1 h, then the test tube was
cooled, and the reaction product was extracted with hot
hexane (30 ml), the extract was washed with 5% NaOH
solution, the organic layer was dried with anhydrous
p-Fluorophenyldiazonium trifluoromethane-
sulfonate (XIIb). Yield 71%, t.decomp. 95–96°C. Found,
%: C 34.40; H 1.7; S 13.0. C H F O S. Calculated, %:
7
4
4
3
C 34.43; H 1.6; S 13.11.
O-Aryl trifluoromethanesulfonates XIIIa and
XIIIb. Into a test tube placed into an oil bath heated to
110–120°C was charged by small portions finely ground
aryldiazonium trifluoromethanesulfonate XIIa or XIIb.
The heating continued for 1 h, then the test tube was
cooled, and the reaction product was extracted with hot
hexane (30 ml), the extract was washed with 5% NaOH
solution, the organic layer was dried with anhydrous
MgSO , filtered, evaporated to 3 ml volume. The
4
separated crystals were filtered off.
m-Fluorophenyl benzothiazol-2-yl(difluoro)-
methanesulfonate (Xa). Yield 61%, t.decomp. 78°C.
1H NMR spectrum, d, ppm: 7.10–7.14 m (3H), 7.42–
MgSO , filtered, evaporated to 3 ml volume. The
4
separated crystals were filtered off. The physical
constants of compounds XIIIa and XIIIb coincided with
the published data [7].
7
8
9
.44 m (1H), 7.56 m (2H ), 8.00 d (1Harom, J 7.6 Hz),
.20 d (1H arom, J 7.8 Hz). F NMR spectrum, d, ppm: –
4.21 s (2F), –109.46 s (1F). Found, %: C 44.83; H 2.20;
arom
1
9
m-Fluorophenyl trifluoromethanesulfonate
N 3.77; S 17.12. C H F NO S . Calculated, %: C 46.75;
1
4
8
3
3 2
1
9
(
XIIIa). Yield 72%. F NMR spectrum, d, ppm: –73.20 s
H 2.23; N 3.90; S 17.81.
(
3F), –108.65 s (1F).
p-Fluorophenyl benzothiazol-2-yl(difluoro)
methanesulfonate (Xb). Yield 53%, mp 57–59°C.
1H NMR spectrum, d, ppm: 7.13–7.17 m (2H), 7.23–
p-Fluorophenyl trifluoromethanesulfonate
1
9
(
XIIIb). Yield 76%. F NMR spectrum, d, ppm: –73.20 s
(
3F), –112.79 s (1F).
7
8
–
.29 m (2H), 7.56 m (2H ), 7.96 d (1Harom, J 7.6 Hz),
.21 d (1Harom, J 7.8 Hz). F NMR spectrum, d, ppm:
94.27 s (2F), –113.76 s (1F). Found, %: C 46.66;
arom
1
9
REFERENCES
H 2.27; N 3.86; S 17.95. C H F NO S . Calculated, %:
C 46.75; H 2.23; N 3.90; S 17.81.
1. Volkov, N.D., Nazaretian, V.P., andYagupolskii, L.M., J. Fluor.
Chem., 1997, vol. 84, p. 135.
1
4
8
3
3 2
2
. Sokol’skii, G.A. and Knunyants, I.L., Izv. Akad. Nauk SSSR.
Ser. Khim., 1967, p. 1289.
Aryldiazonium trifluoromethanesulfonates XIIa
and XIIb. In 5 ml of glacial acetic acid was dissolved
mmol of arylammonium trifluoromethanesulfonates XIa
or XIb prepared from equimolar amounts of arylamine
and trifluoromethanesulfonic acid, and 3 mmol of butyl
nitrite was added. The reaction mixture was left overnight,
the solution was evaporated, to the residue was added
ml of a mixture dichloromethane-pentane, 1:3, the
separated crystals were filtered off and dried in a vacuum.
3. Hanch, C., Leo,A., and Taft, R.W., Chem. Rev., 1991, vol. 91,
3
p. 165.
4. Gunther, H., NMR Spectroscopy: an Introduction, Chichester:
Wiley, 1980.
5
. Yagupol’skii, L.M., Aromaticheskie i geterotsiklicheskie
soedineniya s ftorsoderzhashchimi zamestitelyami (Aromatic
and Heterocyclic Compounds with Fluorocontaining Sub-
stituents), Kiev: Naukova Dumka, 1988.
8
m-Fluorophenyldiazonium trifluoromethane-
sulfonate (XIIa). Yield 76%, t.decomp. 109–110°C.
Found, %: C 34.36; H 1.7; S 13.05. C H F O S . Cal-
6. Quan-Fu, Wang, Yun-Yu, Mao, Shi-Zheng, Zhu, and Chang-
Ming, Hu, J. Fluor. Chem., 1999, vol. 95, p. 141.
7. Yagupol’skii, L.M. and Nazaretyan, V.P., Zh. Org. Khim., 1971,
vol. 7, p. 996.
7
4
4
3
culated, %: C 34.43; H 1.6; S 13.11.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 8 2006