A new one-pot synthesis of difluoro(organylsulfinyl)acetic acid esters

Article abstract of DOI:10.1016/S0022-1139(02)00250-6

A novel single-step method for the synthesis of esters of difluoro(organylsulfinyl)acetic acids, by reacting aromatic compounds with isopropyl chlorosulfinyldifluoroacetate, was developed. The feasibility of transforming the sulfoxide intermediates into c

Full text of DOI:10.1016/S0022-1139(02)00250-6

Journal of Fluorine Chemistry 119 (2003) 59±63
A new one-pot synthesis of di¯uoro(organylsul®nyl)acetic acid esters
Lev M. Yagupolskii*,Andrej V. Matsnev,Nataliya V. Kondratenko
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanskaya Street, 02094Kiev, Ukraine
Received 9 July 2002; received in revised form 5 September 2002; accepted 8 September 2002
Dedicated to Professor Tatlow on the occasion of his 80th birthday.
Abstract
A novel single-step method for the synthesis of esters of di¯uoro(organylsul®nyl)acetic acids,by reacting aromatic compounds with
isopropyl chlorosul®nyldi¯uoroacetate,was developed. The feasibility of transforming the sulfoxide intermediates into corresponding
sul®des and sulfones was demonstrated.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Sulfoxides; Sulfones; Sul®nylation; Di¯uoro(organylsul®nyl)acetates
1. Introduction
compound (1) is prepared from its sodium derivative
described earlier [6] (Scheme 1).
Fluoroalkyl sulfoxides are much less known compared
with the corresponding sul®des or sulfones. However some
of them have already found wide application,for example,
the insecticide Fipronyl [1]. Fluorinated sulfoxides can be
obtained by oxidation of corresponding sul®des [2],by
nucleophilic tri¯uoromethylation of sul®nyl halides and
esters of sul®nic acids with CF3SiMe3 in the presence of
¯uoride ion [3],or by the direct introduction of the group ±
S(O)CF3 into aromatic compounds by the action of sodium
tri¯inate,tri¯uoromethanesulfonic acid and tri¯uorometha-
nesulfonic anhydride [4]. Optically active sulfoxides,with a
¯uorinated alkyl substituent in the a-position relative to the
sul®nyl group,have been obtained for the ®rst time by us [5]
through separation of the diastereomeric salts of the corre-
sponding arylsul®nyldi¯uoroacetic acids. Previously,we
prepared arylsul®nyldi¯uoroacetic acids and their esters
by oxidation of the corresponding sul®des [5],but sulfones
were formed therewith as by-products.
The sul®nyl chloride (1) turned out to be a convenient
reagent to introduce ±S(O)CF2COOR groups into aromatic
compounds in the presence of Friedel-Crafts catalysts. It was
found that,the higher electron density in the ring of the
aromatic substrate 2,the less active catalyst should be used
and in some cases the reaction proceeds in the absence of
any catalyst (Table 1).
N,N-Dimethylaniline and N,N-diethylaniline react with 1,
exothermally and without a catalyst,to give sulfoxides 3a
and 3b,respectively. The corresponding sul®nylated deri-
vatives of N-methylindole and N-methylpyrrole were
obtained in a similar way,without catalysts,but the second
substrate gave a 4:1 mixture of 2- and 3-isomer.
Anisole does not give the desired product under the above
conditions and its reaction with 1 was conducted in the
presence of AlCl3,FeCl 3,SnCl 4 or tri¯uoromethanesulfonic
acid. Heavy tarring occurred with AlCl3 even if the reaction
was initiated at À7 8C (at a lower temperature no reaction
was observed). Iron(III) chloride is also too active and the
yield of the expected product 3e is as low as 40%. Also the
use of tri¯uoromethanesulfonic acid as the catalyst did not
produce the desired result.
2. Results and discussion
Now,we report a one-pot procedure for the synthesis of
arylsul®nyldi¯uoroacetic acid esters from aromatic com-
pounds and isopropyl chlorosul®nyldi¯uoroacetate (1);
The optimum catalyst for the sul®nylation of anisole
with 1 was found to be SnCl4. The reaction when carried
out at 0±20 8C afforded isopropyl 4-methoxyphenylsul®nyl-
di¯uoroacetate (3e) in 85% yield. Also in the sul®nylation
of 1,3-dimethoxybenzene, SnCl4 is the best catalyst.
In contrast to anisole and 1,3-dimethoxybenzene, unsub-
stituted benzene enters into the sul®nylation reaction only in
* Corresponding author. Tel.: ‡380-44-559-03-49;
fax: ‡380-44-573-26-43.
E-mail address: lev@fluor-ukr.kiev.ua (L.M. Yagupolskii).
0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 2 5 0 - 6

60
L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 119 (2003) 59±63
the presence of FeCl3 and the substrate is transformed into
isopropyl phenylsul®nyldi¯uoroacetate (3g) in 65% yield
(Table 1).
Toluene,in the presence of different catalysts,gives a
dif®cult-to-separate mixture of products. Chlorobenzene
and nitrobenzene do not react with 1 even in the presence
of AlCl3.
Scheme 1.
Esters 3a±g were hydrolyzed with alkali into correspond-
ing arylsul®nyldi¯uoroacetic acids (4a±g) (Table 2).
Table 1
Preparation of arylsulfinyldifluoroacetates
Entry
Arene (2)
Time (h)
Product (3)
Isolated yield (%)
No catalyst
FeCl3
SnCl4
a
3
90
85
b
3
c
d
e
4
3
2
80
78a
40
85
80
f
1.5
g
2.5
24
65
h
No reaction
a A 4:1 mixture of 2- and 3-isomer.

L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 119 (2003) 59±63
61
Scheme 2.
Table 2
Preparation of arylsulfinyldifluoroacetic acids
NMR: Varian VXR-300 (288 MHz) (CFCl3 as internal
standard).
4.2. Preparation isopropyl chlorosulfinyldifluoroacetate
(1)
Product
R
Melting
Yield of
(4)
point (8C)
4 (%)
Sodium salt of isopropyl di¯uoro(sul®no)acetate (4 g,
17.8 mmol) was added in small portions to thionyl chloride
(5 ml) at 0 8C. The mixture was stirred,until the evolution of
gas ceased,allowed to warm up to RT and the stirring was
continued for a further 6 h. The mixture was ®ltered,the
unreacted SOCl2 was distilled off and the residue was
puri®ed by distillation to give 3.1 g (65%) 1.
4a
4b
4c
4d
4e
4f
4-Me2NC6H4
4-Et2NC6H4
170±171a
179±180a
180±181a
178±179a
135±136b
162±163b
75±76c
75
70
72
81
80
84
78
1-Methyl-3-indolyl
1-Methyl-2-pyrrolyl
4-MeOC6H4
2,4-(MeO)2C6H3
Ph
4g
The bp is 85±87 8C (18 Torr); 1H NMR (300 MHz,
CDCl3): d 1.37 (d, J ˆ 6 Hz,6H),5.3 (spt,1H). 19F NMR
(282 MHz,CDCl 3/CCl3F): d ˆ À106:4 (d, J ˆ 223 Hz,1F),
À111.0 (d, J ˆ 223 Hz,1F).
a Crystallized from benzene-ethyl acetate.
b Crystallized from benzene.
c Crystallized from benzene-hexane.
Fluorine atoms in compounds 1, 3a±g and 4a±g are diaster-
eotopic,owing to the close proximity to the chiral sulfur center
[5],and magnetically nonequivalent in 19F NMR spectra.
Using 3e as an example,the feasibility was demonstrated
of transforming the sulfoxides into the corresponding sul-
®des and sulfones (Scheme 2). Sulfoxide 3e was converted
into sul®de 5 by the reaction with PCl5,previously used for
reduction of aryl tri¯uoromethyl sulfoxides into aryl tri-
¯uoromethyl sul®des [7]. The oxidation of 3e into sulfone 6
was performed with CrO3 in glacial acetic acid.
4.3. Typical experimental procedure for the reaction
of (1) to give 3a±d
To a stirred solution of N,N-dimethylaniline (2.83 g,
23.4 mmol) in CH2Cl2 (10 ml) cooled to 0 8C was added
agent 1 (1.1 g,5.4 mmol). The mixture was warmed to RT in
30 min and stirred at this temperature for a further 2 h. The
solvent was removed by distillation and the residue was
extracted with diethyl ether. The extract was washed with
water,dried (MgSO ),and concentrated. The residue was
4
chromatographed on silica gel (benzene:hexane 2:1) to give
3a as white crystals.
3. Conclusion
Simple and convenient methods were developed for the
synthesis of arylsul®nyldi¯uoroacetic acids and their esters
and for transformation of the latter into corresponding
sul®des and sulfones.
4.3.1. 4-(Me)2NC6H4S(O)CF2COOPr-i (3a)
1
Melting point 81±82 8C; H NMR (300 MHz,CDCl ):
3
d ˆ 1:26 (d, J ˆ 6 Hz,6H),3.04 (s,6H),5.06 (spt,1H),7.14
(A2B2m,4H).
19F NMR (282 MHz,CDCl 3/CCl3F):
d ˆ À111:2(d, J ˆ 224 Hz,1F), À112.3 (d, J ˆ 224 Hz,
1F). Anal. calcd. for C13H17F2NO3S: C,51.13; H,5.61; N,
4.58; S,10.50. Found: C,51.24; H,5.73; N,4.61; S,10.48.
4. Experimental
4.1. General
4.3.2. 4-(Et)2NC6H4S(O)CF2COOPr-i (3b)
White crystals,mp 63±64 8C; 1H NMR (300 MHz,
CDCl3): d ˆ 1:17±1.29 (m,12H),3.39 (q,4H),5.05 (spt,
1
Boiling and melting points are uncorrected. H NMR:
Varian VXR-300 (300 MHz) (TSM as internal standard). 19
F
1H),7.12 (A 2B2m,4H). 19F NMR (282 MHz,CDCl
/
3

62
L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 119 (2003) 59±63
CCl3F): d ˆ À111:3 (d, J ˆ 226 Hz,1F), À112.4 (d,
J ˆ 226 Hz,1F). Anal. calcd. for C 15H21F2NO3S: C,
54.03; H,6.35; N,4.20; S,9.62. Found: C,53.62; H,
6.15; N,4.41; S,9.74.
NMR (282 MHz,CDCl 3/CCl3F): d ˆ À110:1 (d,
J ˆ 227 Hz,1F), À112.3 (d, J ˆ 227 Hz,1F). Anal. calcd.
for C11H12F2O3S: C,50.37; H,4.61; S,12.22. Found: C,
50.10; H,4.43; S,11.98.
The reaction mixture containing 3e turned red,whereas in
the case of 3f it was violet apparently due to protonation of
the sulfoxide oxygen atom. This suggestion was con®rmed
by formation of the same color on bubbling hydrogen
chloride through a solution of 3e in CH2Cl2.
4.3.3. 1-Methyl-3-indolyl S(O)CF2COOPr-i (3c)
White crystals,mp 102±103 8C; 1H NMR (300 MHz,
CDCl3): d ˆ 0:70 (d, J ˆ 6:2 Hz,6H),3.45 (s,3H),4.58
(spt,1H),6.87±7.52 (m,5H). 19F NMR (282 MHz,CDCl 3/
CCl3F): d ˆ À109:8 (d, J ˆ 222 Hz,1F), À111.3 (d,
J ˆ 222 Hz,1F). Anal. calcd. for C 14H15F2NO3S: C,
53.49; H,4.49; N,4.45; S,10.20. Found: C,53.50; H,
4.70; N,4.41; S,9.98.
4.5. Typical procedure for preparation of acids 4a±g
To a 40% aqueous solution of NaOH (5 ml) was added
ester 3a (0.9 g,3 mmol) and the mixture was stirred at 40 8C
until complete dissolution then it was cooled and ®ltered.
The ®ltrate was acidi®ed to pH 5 and extracted with CH2Cl2.
The extract was washed with a saturated solution of NaCl
and concentrated to leave 4a which was puri®ed by crystal-
lization from benzene-ethyl acetate (Table 2). Compounds
4e and 4g show no depression of mixed mp with authentic
samples of the compounds obtained by another method [5].
4.3.4. 1-Methyl-2-pyrrolyl S(O)CF2COOPr-i (3d)
Oil; 1H NMR (300 MHz,(CD ) CO): d ˆ 1:30 (m,6H);
3 2
3.80,3.94 (s,3H); 5.00 (m,1H),6.29±7.21 (m,3H).
19F
NMR (282 MHz,(CD 3)2CO/CCl3F): 2-isomer, d ˆ À106:7
(d, J ˆ 220 Hz,1F), À110.8 (d, J ˆ 220 Hz,1F); 3-isomer,
d ˆ À109:6 (d, J ˆ 223 Hz,1F), À115.2 (d, J ˆ 223 Hz,
1F). Anal. calcd. for C10H13F2NO3S: C,45.27; H,4.94; N,
5.28; S,12.08. Found: C,45.32; H,4.92; N,5.32; S,12.30.
4.5.1. 4-(Me)2NC6H4S(O)CF2COOH (4a)
1
4.4. Typical experimental procedure for the reaction
of (1) to give 3e±g
Yellow crystals; H NMR (300 MHz,CDCl ): d ˆ 3:01
3
(s,6H),7.17 (A 2B2m,4H). 19F NMR (282 MHz,CDCl /
3
CCl3F): d ˆ À111:2 (d, J ˆ 224 Hz,1F), À112.3 (d,
J ˆ 224 Hz,1F). Anal. calcd. for C 10H11F2NO3S: C,
45.63; H,4.18; N,5.32; S,12.20. Found: C,45.56; H,
4.40; N,5.23; S,11.93.
To anisole (1 ml) was added agent 1 (1.1 g,5.4 mmol) at
0 8C followed by SnCl4 (1.3 g,5 mmol). The temperature
was raised to RT and the mixture was stirred until the
evolution of gas ceased. After completion of the reaction,
the mixture was poured onto crushed ice and extracted with
CH2Cl2. The extract was washed with water,dried (MgSO 4),
concentrated and the residue was puri®ed by chromatogra-
phy (benzene:hexane 4:1) to give 3e as an oily substance.
4.5.2. 4-(Et)2NC6H4S(O)CF2COOH (4b)
1
Yellow crystals; H NMR (300 MHz,CDCl ): d ˆ 1:21
3
(t,6H),3.5 (q,4H),7.14 (A 2B2m,4H). 19F NMR (282 MHz,
CDCl3/CCl3F): d ˆ À109:8 (d, J ˆ 228 Hz,1F), À113.2 (d,
J ˆ 228 Hz,1F). Anal. calcd. for C 12H15F2NO3S: C,49.47;
H,5.19; N,4.80; S,11.01. Found: C,49.51; H,5.30; N,4.82;
S,10.95.
4.4.1. 4-MeOC6H4S(O)CF2COOPr-i (3e)
Oil; 1H NMR (300 MHz,CDCl 3): d ˆ 1:27 (d,
J ˆ 5:8 Hz,6H),3.40 (s,3H),4.87 (spt,1H),7.25
(A2B2m,4H). 19F NMR (282 MHz,CDCl 3/CCl3F): d ˆ
À110:7(d, J ˆ 226 Hz,1F), À112.8 (d, J ˆ 226 Hz,1F).
Anal. calcd. for C12H14F2O4S: C,49.31; H,4.83; S,10.97.
Found: C,49.27; H,4.65; S,10.78.
4.5.3. 1-Methyl-3-indolyl S(O)CF2COOH (4c)
1
Yellow crystals; H NMR (300 MHz,CDCl ): d ˆ 3:51
3
(s,3H),6.78±7.30 (m,5H).
19F NMR (282 MHz,CDCl /
3
CCl3F): d ˆ À110:1 (d, J ˆ 225 Hz,1F), À112.3 (d,
J ˆ 225 Hz,1F). Anal. calcd. for C 11H9F2NO3S: C,
48.52; H,2.96; N,5.14; S,11.77. Found: C,48.34; H,
3.20; N,5.35; S,12.06.
4.4.2. 2,4-(MeO)2C6H3S(O)CF2COOPr-i (3f)
White crystals,mp 56±57 8C; 1H NMR (300 MHz,
CDCl3): d ˆ 1:28 (d, J ˆ 6 Hz,6H),3.73 (s,3H),3.85
(s,3H),5.07 (spt,1H),6.46 (d,
4J ˆ 2 Hz,1H),6.68 (dd,
4.5.4. 1-Methyl-2-pyrrolyl S(O)CF2COOH (4d)
3J ˆ 9 Hz, J ˆ 2 Hz,1H),7.71 (d, 3J ˆ 9 Hz,1H). 19F
NMR (282 MHz,CDCl 3/CCl3F): d ˆ À109:02 (d,
J ˆ 217 Hz,1F), À110.01 (d, J ˆ 217 Hz,1F). Anal. calcd.
for C13H16F2O5S: C,49.44; H,5.00; S,9.95. Found: C,
49.84; H,5.00; S,9.85.
Yellow crystals; 1H NMR (300 MHz,CDCl 3): d ˆ 3:74 (s,
3H),6.31±7.04(m,3H). 19F NMR(282 MHz,CDCl 3/CCl3F):
d ˆ À105:6 (d, J ˆ 225 Hz,1F), À110.5 (d, J ˆ 225 Hz,
1F). Anal. calcd. for C7H7F2NO3S: C,37.67; H,3.16; N,6.28;
S,14.36. Found: C,37.52; H,2.98; N,6.20; S,14.30.
4
4.4.3. PhS(O)CF2COOPr-i (3g)
Oil; 1H NMR (300 MHz,CDCl 3): d ˆ 1:22 (d,
4.5.5. 4-MeOC6H4S(O)CF2COOH (4e)
1H NMR (300 MHz,CDCl 3): d ˆ 3:56 (s,3H),7.92
J ˆ 6:1 Hz,6H),4.12 (spt,1H),7.28±7.92 (m,5H).
19F
(A2B2m,4H),10.70 (br,s,1H).
19F NMR (282 MHz,

L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 119 (2003) 59±63
63
CDCl3/CCl3F): d ˆ À110:7(d, J ˆ 226 Hz,1F), À112.8 (d,
4.7. Preparation of sulfone (6)
J ˆ 226 Hz,1F).
To a solution of 3e (0.9 g,3 mmol) in glacial acetic acid
(7 ml) was added CrO3 (1 g,10 mmol). The mixture was
heated at 60 8C for 3 h,poured into water,and extracted with
CH2Cl2. The extract was washed with water,dried (MgSO 4),
and concentrated to leave sulfone 6 as crystals,mp 87 8C
(from benzene). 1H NMR (300 MHz,CDCl 3): 1.27 (d,
J ˆ 5:8 Hz,6H),3.24 (s,3H),4.30 (spt,1H),7.18
4.5.6. 2,4-(MeO)2C6H3S(O)CF2COOHi (4f)
1H NMR ( 300 MHz,CDCl ): d ˆ 4:18 (s,3H),4.22 (s,
3
3H),7.09 (s,1H),7.20 (d, 3Jˆ3 Hz,1H),7.93 (d, 3J ˆ 3 Hz,
1H),11.02 (br,s,1H). 19F NMR (282 MHz,CDCl 3/CCl3F):
d ˆ À109:02 (d, J ˆ 217 Hz,1F), À110.01 (d, J ˆ 217 Hz,
1F). Anal. calcd. for C10H10F2O5S: C,42.85; H,3.60; S,
11.44. Found: C,42.80; H,3.51; S,11.32.
(A2B2m,4H).
19F NMR (282 MHz,CDCl 3/CFCl3):
À110.7 (s,2F). Anal. calcd. for C 12H14F2O5S: C,46.70;
4.5.7. PhS(O)CF2COOH (4g)
1H NMR (300 MHz,CDCl ): d ˆ 6:46±7.97 (m,5H),
H,4.54; S,10.40. Found: C,46.83; H,4.65; S,10.40.
3
10.87 (br,s,1H).
19F NMR (282 MHz,CDCl 3/CCl3F):
d ˆ À110:1 (d, J ˆ 225 Hz,1F), À112.3 (d, J ˆ 225 Hz,
References
1F).
[1] I.G. Buntain,L.R. Hatton,D.W. Hawkins,C.J. Pearson,D.A. Roberts,
EP 295117 (1988); CA 112 (1988) 35845n.
4.6. Preparation of sulfide (5)
[2] L.M. Yagupolskii,Aromatic and Heterocyclic Compounds with
Fluorine-Containing Substituents,Naukova Dumka,Kiev,1988,
pp. 126±129.
To sulfoxide 3e (1.5 g,5 mmol) was added PCl (1.12 g,
5
5.4 mmol),the mixturewasstirred at RT,untiltheevolutionof
gas ceased,and extracted with CH Cl2. The extract was
[3] R.P. Singh,G. Cao,R.L. Kirchmeier,J.M. Shreeve,J. Org. Chem. 55
(1999) 2873±2877.
2
washed with a 10% aqueous solution of soda and with water,
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[5] A.V. Matsnev,N.V. Kondratenko,L.M. Yagupolskii,Y. L Yagupolskii,
Tetrahedron Lett. 43 (2002) 2949±2952.
(300 MHz,CDCl ): 1.31 (d, J ˆ 6:3 Hz,6H),3.21 (s,3H),
3
4.02 (spt,1H),7.24 (A 2B2m,4H). 19F NMR (282 MHz,
CDCl3/CFCl3): À79.2 (s,2F). Anal. calcd. for C 12H14F2O3S:
C,49.20;H,4.78; S,10.87. Found: C,49.31;H,4.73;S,10.78.
[6] Z.-Y. Yang,D.J. Burton,Heteroatom Chem. 3 (1992) 261.
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