Oxidative nucleophilic substitution of hydrogen in nitroarenes with trifluoromethyl carbanions. Synthesis of trifluoromethyl phenols

Article abstract of DOI:10.1016/j.tet.2004.04.022

Trifluoromethyl carbanions generated from the Ruppert reagent and TASF add to highly electron-deficient nitroarenes to produce σ^H adducts subsequently oxidized with dimethyldioxirane to substituted trifluoromethyl phenols.

Full text of DOI:10.1016/j.tet.2004.04.022

Tetrahedron 60 (2004) 5019–5024
Oxidative nucleophilic substitution of hydrogen in
nitroarenes with trifluoromethyl carbanions.
Synthesis of trifluoromethyl phenols
*
Marek Surowiec and Mieczysław Ma˛kosza
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PL-01-224 Warsaw POB 58, Poland
Received 3 February 2004; revised 18 March 2004; accepted 8 April 2004
Abstract—Trifluoromethyl carbanions generated from the Ruppert reagent and TASF add to highly electron-deficient nitroarenes to produce
sH adducts subsequently oxidized with dimethyldioxirane to substituted trifluoromethyl phenols.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
nucleophilic substitution (VNS).9 On the other hand,
oxidation of the sH adducts with external oxidants such as
KMnO4, DDQ etc. gives substituted nitroarenes, products of
oxidative nucleophilic substitution10 whereas some sH
adducts oxidized with dimethyldioxirane (DMD) are
converted into substituted phenols.11 Trichloromethyl
anions generated by deprotonation of chloroform react
with nitroarenes along the VNS pathway affording nucleo-
philic dichloromethylation.12 The various ways of trans-
forming sH adducts of carbanions to nitroarenes into final
products are shown in Scheme 1.
Pharmaceutical and plant protection agents often contain F
or CF3 substituents and thus methods of introduction of
these groups are of great interest in modern organic
synthesis.1,2 Of particular interest are arenes containing
CF3 groups. There are a few general methods of synthesis of
such arenes, and the main ones are: exchange of chlorine for
fluorine in CCl3 groups of readily available trichloromethyl
arenes and treatment of benzoic acids with SF4.3 On the
other hand, the direct introduction of a CF3 group to arenes
is also possible via Cu catalyzed replacement of halogen
with CF23 carbanion generated from the Ruppert reagent,
CF3SiMe3, or other sources.4 Attempts to replace halogens
or the nitro group in halonitrobenzenes with CF23 , generated
from the Ruppert reagent without a Cu catalyst, gave the
expected products, trifluoromethylnitroarenes, in low
yields.5 There is also one report on oxidative nucleophilic
replacement of hydrogen in trinitrobenzene with a CF32
anion.6
2. Results and discussion
Taking into account the expected higher nucleophilicity of
CF23 anions, that are less stabilized by fluorine substituents
than CCl23 anions, and low rate of elimination of HF from
sH adducts of CF23 anions to nitroarenes, we expected that
there is a good chance for introduction of CF3 groups into
nitroarenes via an oxidative process. Our first attempts of
reaction of CF23 anions generated by treatment of CF3-
SiMe3, (1) with TASF [tris(dimethylamino)sulfonium
difluorotrimethylsilicate] in THF–MeCN with nitro-
benzene, 1-nitronaphthalene, 2-and 4-chloronitrobenzenes
followed by oxidation with Bu4NþMnO42 or DMD gave
negative results. No CF3ArNO2 or CF3ArOH or other
aromatic products containing fluorine were found in the
reaction mixtures, although the nitroarenes were partially
consumed. Since in the reaction mixture we have found
some amounts of nitroaryl acetonitriles it appears that the
generated CF23 anions afforded deprotonation of acetonitrile
and the produced carbanion reacts with nitroarenes. This
supposition was confirmed by treatment of CF3SiMe3 and
2,4,6-trichloronitrobenzene in THF–MeCN with TASF
Introduction of carbon substituents into electron-deficient
arenes can be efficiently executed via nucleophilic substi-
tution of hydrogen with carbanions7 or Grignard reagents.8
The reaction proceeds via addition of these carbon
nucleophiles to the electron-deficient rings in the ortho- or
para- positions to the NO2 group occupied with hydrogen to
form sH adducts that are converted into the final products in
many ways. When the reacting carbanions contain leaving
groups X at the carbanion center, base induced b-elimin-
ation of HX from the sH adducts gives products of vicarious
Keywords: Ruppert reagent; Nitroarenes; Carbanions; Dimethyldioxirane;
Phenols.
*
Corresponding author. Tel.: þ48-22-6318788; fax: þ48-22-6326681;
e-mail address: icho-s@ich.edu.pl
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.04.022

5020
M. Surowiec, M. Ma˛kosza / Tetrahedron 60 (2004) 5019–5024
Scheme 1.
giving 3,5-dichloro-6-nitrophenylacetonitrile in a reason-
able yield 46%. Thus, the THF–MeCN solvent system,
widely used for reaction of aldehydes and ketones with CF32
When a solution of equimolar amounts of the Ruppert
reagent 1, 3-cyanonitrobenzene 2 and TASF in THF–Py
(1:1) at 270 8C was treated with an acetone solution of
DMD, the reaction resulted in formation of a mixture of
three isomeric cyanotrifluoromethyl phenols in a reasonable
overall yield 49%. The ratio of 3-cyano-2-trifluoromethyl-
2a, 3-cyano-4-trifluoromethyl- 2b and 3-cyano-6-trifluoro-
methyl phenol 2c was 5.5:1:6. On the other hand, oxidation
of this system with Bu4NþMnO42 did not produce
trifluoromethyl cyanonitrobenzenes, products of ONSH
reaction. We have already observed that MnO24 oxidation
of the anionic sH adducts is very sensitive to steric
hindrance at the addition site and usually does not proceed
with the sH adducts of carbanions in ortho position to the
NO2 group.10 Interestingly the addition of CF3 carbanions
took place preferentially ortho to the nitro group and as a
consequence oxidation of the sH adducts to 2 with DMD
13
anion generated from CF3SiMe3 cannot be used for its
reactions with nitroarenes. Perhaps due to low rate and
unfavorable equilibrium of the addition of CF23 to
nitroarenes, the main process was acid–base equilibrium
with MeCN. Thus in further studies we used the THF–
pyridine solvent system, as neat THF cannot be used
because it does not dissolve TASF. However, treatment of
nitrobenzene and p-chloronitrobenzene with 1 and TASF in
THF–Py (1:1) at 270 8C, followed by oxidation with
Bu4NþMnO24 or DMD gave negative results. Since the
nitroarenes were mostly recovered we can assume that there
was negligible conversion of ArNO2 into sH adducts.
Hence, we used more electrophilic nitroarenes in our further
studies. The results are presented in Table 1.
Table 1.
Starting nitroarene
Yields of phenols (%)
X
Z
No.
Total
Isomers
CN
H
2
49
3-CN-2-CF3
3-CN-4-CF3
3-CN-6-CF3
2a
2b
2c
22
4
23
CN
4-Cl
H
3
4
63
78
3-CN-4-Cl-2-CF3
3-CN-4-Cl-6-CF3
3a
3b
47
16
NO2
3-NO2-2-CF3
3-NO2-4-CF3
3-NO2-6-CF3
4a
4b
4c
47
18
13
NO2
NO2
4-Br
5
46
3-NO2-4-Br-2-CF3
3-NO2-6-Br-2-CF3
3-NO2-6-Br-4-CF3
5a
5b
5c
29
6
11
5-NO2
6
7
53a
57b
3,5di-NO2-2-CF3
3,5di-NO2-4-CF3
6a
6b
22
31
2-Chloro-3-nitropyridine
2-Cl-3-OH-4-CF3-Py
2-Cl-3-OH-6-CF3-Py
7a
7b
28
29
a
Additionally a,a,a-trifluoro-2,4,6-trinitrotoluene, 33% was obtained.
Additionally 2,20-dichloro-3,30-dinitro-bipyridyl-4,40, 7c, 6% was obtained.
b

M. Surowiec, M. Ma˛kosza / Tetrahedron 60 (2004) 5019–5024
5021
Scheme 2.
gave mostly 2a and 2c. Under similar conditions, other
highly electro-deficient nitroarenes such as m-dinitro-
benzene 3, 3-cyano-4-chloronitrobenzene 4, 2,4-dinitro-
bromobenzene 5, 1,3,5-trinitrobenzene 6 and 2-chloro-3-
nitropyridine 7 were converted into substituted trifluoro-
methylphenols as shown in Scheme 2. Also in the reaction
of these nitroarenes with CF23 anions, the addition
proceeded preferentially ortho to the nitro groups.
Oxidation of sH adducts of CF23 to 2 and 7 with other
oxidants (MnO24 , DDQ, Br2) failed; only when sH adducts
to 4 were treated with Br2 and Et3N, one of the isomeric sH
adducts was converted into 3,5-dinitro-4-trifluoromethyl-
bromobenzene, 4d.
3. Conclusion
Oxidation of the sH adducts of CF23 anions to polynitro-
arenes 4, 5 and 6 creates an interesting question: which of
the negatively charged NO2 groups is oxidized by DMD and
converted into the OH group? Surprising there was not
significant difference between rates of oxidation of such
nitro groups located ortho and para to the addition site. For
instance in the sH adduct of CF3 to 4 ratio of the
corresponding rates equals 0.72.
We have shown that the CF23 anion generated by treatment
of the Ruppert reagent with TASF adds to nitroarenes
provided they show sufficiently high electron deficiency. In
our hands the oxidation of such sH adducts proceeds
satisfactorily only with dimethyldioxirane giving substi-
tuted trifluoromethyl phenols.
4. Experimental
The structures of the trifluoromethyl phenols obtained by
oxidation of the sH adducts of CF23 anions to nitroarenes
4.1. General remarks
were determined on the basis of analysis of 1H, 13C and 19
F
NMR spectra. For this purpose, mass spectra were also very
helpful. In MS of all ortho CF3 phenols, there were well
pronounced ions [M220]þ formed by elimination of HF.
Melting points are uncorrected. Infrared spectra were
recorded on a Perkin–Elmer FT-IR spectrometer. NMR
spectra were measured at 400 MHz on a Mercury-400BB or
at 200 MHz on a Gemini-200BB spectrometers. Chemical
shifts are reported in ppm relative to tetramethylsilane as
internal standard. Mass spectra were obtained on AMD 604
Inectra GmbH instrument using EI, appropriate isotope
patterns were observed. Analytical TLC was carried out on
Merck alufolien sheets Kieselgel 60 F254. For preparative
HPLC Merck-Hitachi equipment was used with pump
L-7100 detector VL-7400, using hexane and ethyl acetate
as a solvent. For column chromatography silica gel 230–
400 mesh, Merck was used. Solvents, nitroarenes and TASF
were used as received from the manufacturers except for
tetrahydrofuran that was distilled over potassium benzo-
phenone ketyl before use. The Ruppert reagent was a gift
from Dr A. Marhold (Bayer AG).
Although yields of the trifluoromethyl phenols were rather
moderate (46–78%), unreacted nitroarenes were recovered
and thus there was an excellent material balance of the
nitroarenes, usually above 90%. On this basis we suppose
that the sH adducts of CF3 anions, once formed, are
efficiently oxidized by DMD to phenols. However, the
degree of conversion of CF23 into the sH adducts is not
very high in spite of high electrophilicity of the arenes. This
is perhaps due to fast dissociation of CF23 to difluoro-
carbene.14
Formation of the sH adducts of CF23 to nitroarenes is
accompanied with coloration of the mixture (orange, red,
blue, etc) and oxidation of these adducts with DMD results
in disappearance of the color. Usually, oxidation is
completed within a few min. Only oxidation of sH adducts
of 6 required a few hours for completion. Because of that,
oxidation of the sH adducts to 1,3,5-trinitrobenzene with
DMD gave, besides the expected phenols 6a and 6b
substantial quantities of the ONSH product a,a,a-trifluoro-
trinitrotoluene, 6c. Surprisingly oxidation of the corre-
sponding sH adduct to 2-chloro-3-nitropyridine 7 also gave
small amount of the bipyridine 7c. This byproduct is
perhaps formed via oxidation of the deprotonated pyridine
by analogy to reported observations.15 In this case, CF32
acted as a base abstracting a proton from the pyridine ring.
This process shows that CF32 despite being a strong base is a
weak nucleophile and can be considered as a hard
nucleophile.
Acetone solution of DMD was prepared according to the
described procedure.16
4.2. Reaction of the Ruppert reagent with 2,4,6-
trichloronitrobenzene in the presence of TASF in
THF/MeCN system
To a stirred solution of 1 (0.6 mmol) and nitroarene
(0.5 mmol) in THF (5 mL) at 270 8C under argon, TASF
(153 mg, 0.5 mmol) dissolved in MeCN (1 mL) was added
dropwise, the mixture was stirred for 30 min and the cooling
bath was removed. After 30 min of further stirring, aqueous
HCl (1 mL) was added. The reaction mixture was dried over
anhydrous MgSO4, the solid phase was filtered off and
washed with dichloromethane (20 mL). The solvents were

5022
M. Surowiec, M. Ma˛kosza / Tetrahedron 60 (2004) 5019–5024
evaporated (25 8C, 15 Torr) and the product was purified by
column chromatography using hexane–ethylacetate 20:1 as
eluent.
118.0, 96.6. IR (KBr): 3234, 2259, 1980, 1591, 1473, 1316,
1268, 1148, 1108, 1041, 983, 808, 753. Anal. calcd for
C8H4F3NO: C, 51.35; H, 2.15; N, 7.49. Found: C, 50.99; H,
1.85; N, 7.20.
4.2.1. 3,5-Dichloro-2-nitrophenylacetonitrile. Yield
54 mg, 46%, colorless crystals, mp 69–70 8C (EtOH). HR
EIMS calcd for C8H4N2O325Cl2 M¼229.9650. Found:
229.9654. 1H NMR (400 MHz, CDCl3): 7.61–7.59 (m,
1H), 7.85–7.70 (m, 1H), 3.81–3.75 (m, 2H). 13C NMR
(100 MHz, CDCl3): 137.8, 132.5, 130.8, 128.3, 127.7,
125.7, 114.6, 20.3. Anal. calcd for C8H4N2O2Cl2: C, 41.59;
H, 1.75; N, 12.13, Cl, 30.69. Found: C, 41.68; H, 1.49; N,
12.19, Cl, 30.79.
4.3.4. 4-Chloro-3-cyano-2-trifluoromethylphenol (3a).
Yield 52 mg, 47%, yellow crystals, mp 201–202 8C
(CH2Cl2). EIMS m/z (%): 223 (9), 221 (29), 203 (18), 201
(100), 175 (13), 173 (41). HR EIMS calcd for C8H3ONF335Cl
M¼220.9855. Found: 220.9858. 1H NMR (400 MHz,
acetone-d6): 10.50 (s broad, 1H), 7.78 (d, 1H, J¼8.9 Hz),
7.48 (d, 1H, J¼8.9 Hz). 19F NMR (376 MHz, acetone-d6):
254.33. 13C NMR (100 MHz, acetone-d6): 156.6, 135.4,
129.2 (q, J¼5 Hz), 124.6, 123.1 (q, J¼274 Hz), 123.0 (q,
J¼30 Hz), 113.8, 96.6. Anal. calcd for C8H3F3NOCl: C,
43.37; H, 1.36; N, 6.32. Found: C, 43.16; H, 1.12; N, 6.17.
4.3. General procedure for oxidation of the sH adducts
of CF23 to nitroarenes with DMD
To a stirred solution of 1 (0.6 mmol) and nitroarene
(0.5 mmol) in THF (5 mL) at 270 8C under argon, TASF
(153 mg, 0.5 mmol) dissolved in pyridine (1 mL) was added
dropwise and the mixture was stirred for 5 min. Water
(9 mL, 0.5 mmol) and than an acetone solution of DMD (ca.
0.6 mmol, 10 mL of ca. 0.06 M) was added to the mixture.
After 15 min of further additional stirring, dilute HCl
(1 mL) was added and the cooling bath was removed. A
mixture of isomeric trifluoromethylphenols was extracted
from the reaction mixture with aqueous NaOH and after
acidification of the aqueous layer was separated by
preparative HPLC.
4.3.5. 4-Chloro-3-cyano-6-trifluoromethylphenol (3b).
Yield 18 mg, 16%, yellow crystals, mp 168–169 8C
(CH2Cl2). EIMS m/z (%): 223 (18), 221 (57), 203 (34),
202 (16), 201 (100), 175 (24), 173 (70). HR EIMS calcd for
1
C8H3ONF335Cl M¼220.9855. Found: 220.9862. H NMR
(400 MHz, acetone-d6): 7.84 (d, 1H, J¼0.6 Hz), 7.54 (s,
1H), 3.4 (s broad, 1H). 19F NMR (376 MHz, acetone-d6):
264.5. Anal. calcd for C8H3F3NOCl: C, 43.37; H, 1.36; N,
6.32. Found: C, 43.21; H, 1.28; N, 6.34.
4.3.6. 3-Nitro-2-trifluoromethylphenol (4a). Yield 49 mg,
47%, colorless crystals, mp 136–137 8C (CH2Cl2/hexane).
EIMS m/z (%): 208 (9), 207 (100), 188 (4), 187 (2), 177
(13), 161 (80), 149 (28), 133 (18), 113 (43). HR EIMS calcd
The products 7a and 7b were isolated in another manner.
The reaction mixture was dried over anhydrous MgSO4, the
solid phase was filtered off and washed with acetone
(20 mL). The solvents were evaporated (25 8C, 15 Torr) and
the products were purified by preparative HPLC.
1
for C7H4O3NF3 M¼207.0143. Found: 207.0150. H NMR
(acetone-d6, 400 MHz): 10.36 (s, 1H), 7.73–7.67 (m, 1H),
7.38 (d, 1H, J¼8.4 Hz), 7.28 (d, 1H, J¼7.9 Hz). 19F NMR
(acetone-dd, 376 MHz): 259.40. 13C NMR (acetone-dd,
100 MHz): 157.9, 135.3, 123.0 (q, J¼271 Hz), 121.2, 115.1,
108.6 (q, J¼34 Hz), 96.6. IR (KBr): 3428, 1617, 1531,
1465, 1376, 1338, 1306, 1154, 1129, 1042, 961, 823, 807,
740.
4.3.1. 3-Cyano-2-trifluoromethylphenol (2a). Yield
21 mg, 22%, colorless crystals, mp 157–158 8C (CH2Cl2).
EIMS m/z (%): 187 (85), 168 (17), 167 (91), 139 (100), 138
(4), 120 (3), 112 (9). HR EIMS calcd for C8H4ONF3
M¼187.0245. Found: 187.0251. 1H NMR (400 MHz,
CDCl3): 7.52 (m, 1H), 7.41 (d, 1H, J¼7.7 Hz), 7.24 (d,
1H, J¼8.3 Hz), 6.70 (s, broad, 1H). 19F NMR (376 MHz,
acetone-d6): 258.1. Anal. calcd for C8H4F3NO: C, 51.35;
H, 2.15; N, 7.49. Found: C, 51.17; H, 1.89; N, 7.31.
4.3.7. 3-Nitro-4-trifluoromethylphenol (4b). Yield 19 mg,
18%, colorless crystals, mp 210–211 8C (CH2Cl2). EIMS
m/z (%): 208 (8), 207 (100), 188 (9), 187 (79), 177 (1), 161
(32), 141 (26), 138 (33), 113 (88). HR EIMS calcd for
C7H4O3NF3 M¼207.0143. Found: 207.0137. 1H NMR
(CDCl3, 400 MHz): 7.69 (d, 1H, J¼8.7 Hz), 7.35 (d, 1H,
J¼2.3 Hz), 7.06–7.00 (m, 1H), 6.38 (s broad, 1H). 19F
NMR (acetone-dd, 376 MHz): 259.56. 13C NMR (CDCl3,
100 MHz): 156.1, 134.8, 129.0, 123.9, 118.79 (q, J¼31 Hz),
112.3 (q, J¼207 Hz), 96.0.
4.3.2. 3-Cyano-4-trifluoromethylphenol (2b). Yield
4 mg, 4%, colorless crystals. EIMS m/z (%): 187 (100),
168 (8), 139 (75), 120 (10). HR EIMS calcd for C8H4ONF3
M¼187.0245. Found: 187.0249. 1H NMR (400 MHz,
CDCl3): 7.57 (d, 1H, J¼8.7 Hz), 7.27 (s, 1H), 7.19 (d, 1H,
J¼8.7 Hz), 6.68 (s broad, 1H). 19F NMR (376 MHz,
acetone-d6): 260.20.
4.3.8. 3-Nitro-6-trifluoromethylphenol (4c). Yield 14 mg,
13%, yellow oil. EIMS m/z (%): 208 (8), 207 (100), 189 (1),
187 (88), 161 (32), 141 (57), 113 (73). HR EIMS calcd for
C7H4O3NF3 M¼207.0143. Found: 207.0137. 1H NMR
(acetone-d6, 400 MHz): 7.93–7.91 (m, 1H), 7.87 (d, 1H,
4.3.3. 3-Cyano-6-trifluoromethylphenol (2c). Yield
22 mg, 23%, colorless crystals, mp 188–189 8C (CH2Cl2).
EIMS m/z (%): 187 (82), 168 (18), 167 (100), 139 (90), 120
(3), 112 (8). HR EIMS calcd for C8H4ONF3 M¼187.0245.
Found: 187.0249. 1H NMR (400 MHz, CDCl3): 7.64 (d, 1H,
J¼8.1 Hz), 7.30 (d, 1H, J¼8.1 Hz), 7.28 (s, 1H), 6.60 (s
broad, 1H). 19F NMR (376 MHz, acetone-d6): 263.0. 13C
NMR (100 MHz, acetone-d6): 156.7, 128.9 (q, J¼5 Hz),
124.1 (q, J¼272 Hz), 123.8, 121.6 (q, J¼31 Hz), 120.9,
J¼0.5 Hz), 7.86–7.84 (m, 1H). 19F NMR (acetone-d**d
,
376 MHz): 262.92.
4.3.9. 4-Bromo-3-nitro-2-trifluoromethylphenol (5a).
Yield 42 mg, 29%, orange oil. EIMS m/z (%): 287 (98),
285 (100), 267 (45), 265 (45), 241 (33), 239 (31), 218 (22),
216 (22), 193 (42), 191 (44), 112 (57), 86 (45). HR EIMS

M. Surowiec, M. Ma˛kosza / Tetrahedron 60 (2004) 5019–5024
5023
calcd for C7H3O3NF739Br M¼284.9248. Found: 284.9253.
1H NMR (400 MHz, CDCl3): 7.57 (dd, 1H, J¼8.9, 0.6 Hz),
6.92 (dd, 1H, J¼8.9, 0.4 Hz), 5.10 (s broad, 1H). 19F NMR
(376 MHz, CDCl3): 259.46.
C10H4O4N437Cl35Cl M¼315.9580. Found: 315.9578. 1H
NMR (400 MHz, CDCl3): 8.67 (d, 2H, J¼4.9 Hz), 7.32
(d, 2H, J¼4.9 Hz). 13C NMR (100 MHz, CDCl3): 151.0,
143.9, 143.4, 136.1, 122.5. Anal. calcd for C10H4O4N4O3-
Cl2: C, 38.12; H, 1.28; N, 17.78. Found: C, 38.08; H, 1.31;
N, 17.47.
4.3.10. 6-Bromo-3-nitro-2-trifluoromethylphenol (5b).
Yield 9 mg, 6%, orange oil. EIMS m/z (%): 287 (13), 285
(13), 267 (4), 265 (4), 241 (7), 239 (6), 86 (100). HR EIMS
calcd for C7H3O3NF739Br M¼284.9248. Found: 284.9242.
1H NMR (400 MHz, CDCl3): 8.21 (d, 1H, J¼8.8 Hz), 7.95
(d, 1H, J¼8.8 Hz), 7.38 (s, 1H). 19F NMR (376 MHz,
CDCl3): 259.23.
4.4. Oxidation of sH adducts of CF23 to m-dinitro-
benzene with Br2
To a stirred solution of 1 (0.6 mmol) and nitroarene
(0.5 mmol) in THF (5 mL) at 270 8C under argon, TASF
(153 mg, 0.5 mmol) dissolved in pyridine (1 mL) was added
dropwise and the mixture was stirred for 5 min. Bromine
(0.6 mmol, 97 mg) dissolved in THF (1 mL) was added to
the mixture and after 5 min triethylamine (0.5 mL) was
added. The cooling bath was removed. The solids were
filtered off and washed with dichloromethane (20 mL). The
solvents were evaporated (25 8C, 15 Torr) and the product
was purified by column chromatography using hexane as an
eluent. In the cases of use 2 and 7 we could not find any
defined products, on GCMS we observed traces (,10%) of
products of ONSH process. In case of using 4 we isolated
starting nitroarene 25% and 4d (46%).
4.3.11. 6-Bromo-3-nitro-4-trifluoromethylphenol (5c).
Yield 17 mg, 11%, orange oil. EIMS m/z (%): 287 (13),
285 (13), 257 (4), 255 (4), 241 (7), 239 (7), 229 (4), 227 (4),
101 (23), 100 (25), 86 (100). HR EIMS calcd for C7H3O3-
NF739Br M¼284.9248. Found: 284.9257. 1H NMR
(400 MHz, CDCl3): 7.85 (s, 1H), 7.34 (s, 1H), 5.6 (s
broad, 1H). 19F NMR (376 MHz, CDCl3): 258.81.
4.3.12. 3,5-Dinitro-4-trifluoromethylphenol (6a). Yield
39 mg, 31%, colorless crystals, mp 163–165 8C (CH2Cl2).
EIMS m/z (%): 253 (9), 252 (100), 183 (22), 160 (39), 159
(9), 135 (20), 132 (54). HR EIMS calcd for C7H3O5N2F3
M¼251.9994. Found: 251.9993. 1H NMR (200 MHz,
acetone-d6): 7.69 (d, J¼0.5 Hz). 19F NMR (376 MHz,
acetone-d6): 255.8 (t, J¼0.5 Hz).
4.4.1. 4-Bromo-2,6-dinitro-a,a,a-trifluorotoluene 4d.
Yield 73 mg, 46%, yellow crystals, mp 108–109 8C
(EtOH). EIMS m/z (%): 316 (71), 314 (72), 297 (4), 295
(4), 224 (7), 222 (7), 212 (9), 210 (9), 174 (10), 172 (8), 143
(100). HR EIMS calcd for C7H2O4N2F739Br M¼313.9150.
4.3.13. 3,5-Dinitro-2-trifluoromethylphenol (6b). Yield
28 mg, 22%, yellow oil. EIMS m/z (%): 253 (6), 252 (81),
233 (12), 232 (100), 183 (7), 160 (27), 132 (30). HR EIMS
1
Found: 313.9156. H NMR (CDCl3, 400 MHz): 8.09 (d,
J¼0.6 Hz). 19F NMR (CDCl3, 376 MHz): 257.34. 13C
NMR (CDCl3, 100 MHz): 149.8, 130.3, 129.6, 125.4 (q,
J¼305 Hz), 121.4, 118.7, 116.3 (q, J¼36 Hz).
1
calcd for C7H3O5N2F3 M¼251.9994. Found: 251.9991. H
NMR (400 MHz, acetone-d6): 8.18 (d, 1H, J¼0.7 Hz), 7.68
(d, 1H, J¼0.7 Hz). 19F NMR (376 MHz, acetone-d6): 259.2
(t, J¼0.7 Hz).
Acknowledgements
4.3.14. a,a,a-Trifluoro-2,4,6-trinitrotoluene (6c). Yield
46 mg, 33%, colorless crystals, mp 88–89 8C (CH2Cl2)
(lit.17 89 8C). EIMS m/z (%): 282 (8), 281 (100), 159 (10),
143 (68), 131 (22). HR EIMS calcd for C7H2O6N3F3
M¼280.9896. Found: 280.9888. 1H NMR (200 MHz,
acetone-d6): 8.80 (s). 19F NMR (376 MHz, acetone-d6):
257.5.
We are indebted to Dr. A. Marhold (Bayer AG) Leverkusen
for the generous gift of the Ruppert reagent.
References and notes
4.3.15. 2-Chloro-3-hydroxy-4-trifluoromethylpyridine
(7a). Yield 28 mg, 28%, yellow oil. HR EIMS calcd for
1. Welch, J. T.; Eswarakrishnan, S. Fluorine in Bioorganic
Chemistry. Wiley: New York, 1991.
1
C6H3NOF335Cl M¼196.9855. Found: 196.9848. H NMR
(400 MHz, acetone-d6): 8.76 (d, 1H, J¼5.0 Hz), 7.77 (d,
1H, J¼5.0 Hz), 7.40 (s broad, 1H). 19F NMR (376 MHz,
acetone-d6): 265.09.
2. Hiyama, T. Organofluorine Compounds: Chemistry and
Applications; Springer: Berlin, 2000.
3. Hudlicky, M. Chemistry of Organic Fluorine Compounds I;
2nd ed. Ellis Horwood: New York, 1992; pp 96–106 and 154–
158. Hudlicky, M. In Chemistry of Organic Fluorine
Compounds II; Hudlicky, M., Pavlath, A. E., Eds.; American
Chemical Society: Washington, 1995; pp 178–184 and 243–
249. Houben-Weyl: Methods of Organic Chemistry; Baasner,
B., Hagemann, H., Tatlow, J. C., Eds.; Thieme: Stuttgart,
1999; Vol. E10a. Miethchen, R. pp 133–141, 348–370,
Yagupolskii, L. M. pp 509–525 and Dmowski, W. pp 321–
405.
4.3.16. 2-Chloro-3-hydroxy-6-trifluoromethylpyridine
(7b). Yield 28 mg, 28%, yellow oil. HR EIMS calcd for
1
C6H3NOF335Cl M¼196.9855. Found: 196.9843. H NMR
(400 MHz, acetone-d6): 8.59 (s broad, 1H), 8.07 (d, 1H,
J¼4.8 Hz), 7.33 (d, 1H, J¼4.8 Hz). 19F NMR (376 MHz,
acetone-d6): 264.92.
4.3.17. 2,20-Dichloro-3,30-dinitro-4,40-bipyridyl (7c).
Orange crystals, mp 189–190 8C (EtOH). EIMS m/z (%):
316 (7), 314 (11), 270 (6), 268 (9), 242 (18), 240 (13), 177
(8), 175 (7), 153 (32), 151 (100). HR EIMS calcd for
4. Cottet, F.; Schlosser, M. Eur. Org. J. Chem. 2002, 327. Duan,
J.-X.; Su, D.-B.; Wu, J.-P.; Chem, Q.-Y. J. Fluorine Chem.
1994, 66, 167.

5024
M. Surowiec, M. Ma˛kosza / Tetrahedron 60 (2004) 5019–5024
´
5. Adams, D. J.; Clark, J. H.; Hansen, L. B.; Sanders, V. C.;
Stewart, J. T. J. Chem. Soc. Perkin Trans. 1 1998, 3081.
6. Stahly, G. P. J. Fluorine Chem. 1989, 45, 431.
11. Adam, W.; Ma˛kosza, M.; Stalinski, K.; Zhao, C.-G. J. Org.
Chem. 1998, 63, 4390. Adam, W.; Ma˛kosza, M.; Zhao, C.-G.;
Surowiec, M. J. Org. Chem. 2000, 65, 1099.
7. Terrier, F. Chem. Rev. 1982, 82, 78. Terrier, F. Nucleophilic
Aromatic Displacement; Chemie: Weinheim, 1991.
Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.
Nucleophilic Aromatic Substitution of Hydrogen; Academic
Press: San Diego, 1994. Ma˛kosza, M. Russ. Chem. Bull. 1996,
45, 491.
12. Ma˛kosza, M.; Owczarczyk, Z. J. Org. Chem. 1989, 54, 5094.
13. Noyori, R.; Yokoyama, K.; Sakata, J.; Kuwajima, I.;
Nakamura, E.; Shimizu, M. J. Am. Chem. Soc. 1977, 99,
1265. Nakamura, E.; Shimizu, M.; Kuwajima, I.; Sakata, J.;
Yokoyama, K.; Noyori, R. J. Org. Chem. 1983, 48, 932.
14. Hine, J. Physical Organic Chemistry; McGraw-Hill: New
York, 1962; p. 486.
8. Bartoli, G. Acc. Chem. Res. 1984, 17, 109. Ma˛kosza, M.;
Surowiec, M. J. Organometal. Chem. 2001, 624, 167.
9. Ma˛kosza, M.; Winiarski, J. Acc. Chem. Res. 1987, 20, 289.
Ma˛kosza, M. Pol. J. Chem. 1992, 66, 3. Ma˛kosza, M.;
Wojciechowski, K. Liebigs Ann. Recuil 1997, 1805. Ma˛kosza,
M.; Kwast, A. J. Phys. Org. Chem. 1998, 11, 341.
´ ´´
15. Epsztajn, J.; Bieniek, A.; Brzezinski, J. Z.; Jozwiak, A.
´
Tetrahedron Lett. 1983, 4735. Mongin, F.; Trecomt, F.;
Queguiner, G. Terahedron Lett. 1999, 5483.
16. Adam, W.; Białas, J.; Hadjiarapoglou, L. Chem. Ber. 1991,
124, 2377.
´
10. Ma˛kosza, M.; Stalinski, K. Pol. J. Chem. 1999, 73, 151.
17. Gray, D. N.; Schmidt, J. J. E.; Smith, C. D. J. Chem. Soc. 1960,
2243.
´
Ma˛kosza, M.; Stalinski, K. Chem. Eur. J. 1997, 3, 2025.
´
Ma˛kosza, M.; Stalinski, K. Synthesis 1998, 1631. Ma˛kosza,
´
M.; Stalinski, K. Tetrahedron 1998, 54, 8797.