Mendeleev Commun., 2006, 16(3), 135–134
The obtained difluoromethyl iodides were introduced into
reactions with aldehydes and unsaturated compounds, and reduc-
tion reaction.
Thus, p-chlorophenylsulfinyldifluoromethyl iodide reacts with
p-methylbenzaldehyde in the presence of tetrakis(diethylamino)-
ethylene (TDAE) and gives corresponding secondary alcohol 4
in 60% yield as a diastereomer mixture. Likewise, the p-chloro-
phenylsulfonyldifluoromethyl iodide reacts with p-methylbenz-
aldehyde.¶
We established that it is possible to obtain the corresponding
optically active sulfinyldifluoromethyl iodides and difluoromethyl
sulfoxides from optically active sulfinyldifluoroacetic acids.
Optically active (+)-p-chlorophenylsulfinyldifluoroacetic acid
(98% ee) was taken as a model compound. The optically active
difluoromethyl iodide containing the sulfinyl group was obtained
from this acid according to the above method in 75% yield.‡‡
O
S
O
*
*
S
H
HgO, I2
C2H4Cl2
CF2COOH
CF2I
S(O)n
O
CF2I
+
Cl
Cl
7
Cl
Me
[a]D20 +171.4° (c 0.01, CH2Cl2), 98% ee
1c n = 1
3c n = 2
TDAE – 15 to 25 °C
OH
Scheme 5 Synthesis of optically active p-chlorophenylsulfinyldifluoro-
methyl iodide.
S(O)n
CF2
H
The optically active p-chlorophenyldifluoromethyl sulfoxide
was synthesised in a reaction of (+)-p-chlorophenylsulfinyl-
difluoromethyl iodide with zinc in DMF.§§
Cl
Me
4 n = 1
5 n = 2
O
S
O
Scheme 3 Reaction of 1c and 3c with p-methylbenzaldehyde.
*
*
S
p-Chlorophenylsulfinyldifluoromethyl iodide reacts with zinc
in dimethylformamide (DMF) at room temperature to form
corresponding difluoromethylsulfoxide 6 in high yield.††
CF2I
CF2H
Zn, DMF
Cl
Cl
[a]D20 +227.8° (c 0.01, CH2Cl2), 98% ee
7
8
O
S
O
S
CF2I
CF2H
Zn, DMF
Scheme 6 Synthesis of optically active p-chlorophenyldifluoromethyl
sulfoxide.
Cl
Cl
The enantiomer purity was defined using 19F NMR spectro-
scopy in the presence of a chiral shift reagent, (+)-phenyl-
tert-butylthiophosphonic acid.11
Thus, we found a new method for the synthesis of compounds
with the difluoromethyliodide group directly connected to sulfide
or sulfonyl groups. Sulfoxides and their optically active forms
with difluoroiodomethyl and difluoromethyl groups bound to
sulfur were synthesised for the first time.
1c
6
Scheme 4 Reaction of 1c with zinc.
An attempt to add sulfinyldifluoromethyl iodide to the double
bond of styrene under UV irradiation of the reaction mixture
yielded a hard-to-separate mixture of products. The use of azo-
isobutyronitrile (AIBN) as a catalyst did not cause the addition
of difluoromethyl iodides to double bonds, and benzoyl peroxide
oxidised the sulfinyldifluoromethyl group to sulfone.
Earlier, we have elaborated the synthesis of the first optically
active fluorocontaining sulfoxides with fluorinated groups bounded
directly to the centre of optical activity, namely, sulfur.8
References
1 C. Wakselman and A. Lantz, in Organofluorine Chemistry, ed. R. E.
Banks, Plenum Press, New York, 1994, pp. 177–190.
2 R. D. Chambers, Fluorine in Organic Chemistry, Blackwell Publishing,
Oxford, 2004, pp. 122–126.
¶
The synthesis of p-chlorophenylsulfinyl- and sulfonyldifluoromethyl-
p-tolylcarbinols 4 and 5. Iodide 1c or 3c (0.02 mol) was added to 1 ml
of p-methylbenzaldehyde, the mixture was cooled to –15 °C under argon,
after that 0.02 mol of TDAE was added with intense stirring. The reaction
mixture was kept at this temperature for 1.5 h. Then, the temperature was
slowly raised to room temperature, the mixture was stirred until the orange-
brown colour disappeared. After the end of the reaction, water was added,
the mixture was acidified to pH 4–5. The product was extracted by
3×5 ml of CH2Cl2. The combined organic phase was washed with ice-cold
water and dried over MgSO4. The solvent was distilled off, the product
was purified by column chromatography (ethyl acetate–hexane).
3 P. Kirsch, Modern Fluoroorganic Chemistry I, Wiley-VCH, Weinheim,
2004, pp. 91–98.
‡‡ Preparation of optically active p-chlorophenylsulfinyldifluoromethyl
iodide 7. Mercury oxide (0.05 mol) was added to a solution of 0.05 mol
of optically active p-chlorophenylsulfoxydifluoracetic acid in 10 ml of
anhydrous dichloroethane. The mixture was heated to the boiling point
and stirred for 30 min until the precipitate of mercury salt formed. Then,
the solution of 0.05 mol of iodine in 10 ml of anhydrous dichloroethane
was added dropwise to the reaction mixture. The mixture was refluxed
with stirring for 4 h. The end of the reaction was controlled by TLC.
Then, the reaction mixture was cooled down to 10 °C and filtered. The
solvent was distilled off; the product was purified by column
1
4: H NMR [(CD3)2CO] d: 2.66 (d, 3H), 4.69 (br. s, 1H), 5.49–5.73
(m, 1H), 7.47–7.97 (m, 8H). 19F NMR, d: –111.2 (ddd, JFF 217 Hz,
JFH 14 Hz), –111.5 (d, JFF 222 Hz), –117.5 (ddd, JFF 222 Hz, JFH 23 Hz),
–118.9 (ddd, JFF 217 Hz, JFH 14 Hz). MS, m/z (RI): 330 (4.5), 162 (37),
160 (100), 121 (30), 112 (27).
1
1
5: H NMR [(CD3)2CO] d: 2.43 (s, 3H), 4.89 (br. s, 1H), 5.51 (dd,
chromatography (benzene–hexane); oil. H NMR (CDCl3) d: 7.54–7.69
1H, J1 20 Hz, J2 3 Hz), 7.17–7.93 (m, 8H). 19F NMR, d: –104.5 (d,
JFF 234 Hz), –118.2 (dd, JFF 234 Hz, JFH 20 Hz). MS, m/z (RI): 175
(0.2), 170 (2), 121 (100), 94 (11).
(m, 4H). 19F NMR, d: –44.4 (d, 2F, J 172 Hz), –49.0 (d, 2F, J 172 Hz).
Found (%): I, 37.54; S, 9.23. Calc. for C7H4ClIF2OS (%): I, 37.79; S,
9.52.
†† Preparation of p-chlorophenyldifluoromethyl sulfoxide 6. Zinc dust
(0.02 mol) was added to a solution of iodide 1c in 2 ml of DMF and
stirred at room temperature until the iodide disappeared, according to
TLC; then, the mixture was poured into water. The product was extracted
by 3×5 ml of diethyl ether. The combined organic phase was washed with
2×5 ml of cold water and dried over MgSO4. The solvent was distilled
off, the product was purified by column chromatography (benzene–
hexane); mp 74–75 °C. 1H NMR (CDCl3) d: 5.6 (t, 1H, J 54 Hz),
7.54–7.63 (m, 4H). 19F NMR, d: –119.7 (dd, 2F, J 252 Hz), –121.5
(dd, 2F, J 252 Hz). Found (%): C, 40.33; H, 2.43; S, 15.30. Calc. for
C7H5ClF2OS (%): C, 39.91; H, 2.38; S, 15.23.
§§ Preparation of optically active p-chlorophenylfluoromethyl sulfoxide 8.
Zinc dust (0.02 mol) was added to a solution of iodide 7 in 2 ml of DMF,
the mixture was stirred at room temperature until iodide 7 disappeared
according to TLC data. After the end of the reaction, the mixture was
poured into water. The product was extracted with 3×5 ml of diethyl ether.
The combined organic phase was washed with 2×5 ml of cold water and
dried over MgSO4. The solvent was distilled off; the product was purified
1
by column chromatography (benzene–hexane); mp 91–92 °C. H NMR
(CDCl3) d: 6.0 (t, 1H, J 55 Hz), 7.57–7.68 (m, 4H). 19F NMR, d: –119.0
(dd, 2F, J 252 Hz), –120.6 (dd, 2F, J 252 Hz). Found (%): C, 39.71;
H, 2.55; S, 15.52. Calc. for C7H5ClF2OS (%): C, 39.91; H, 2.38; S, 15.23.
Mendeleev Commun. 2006 133