Hydroxylation of nitro-(pentafluorosulfanyl)benzenes via vicarious nucleophilic substitution of hydrogen

Article abstract of DOI:10.1016/j.tetlet.2011.06.011

Para- and meta-nitro-(pentafluorosulfanyl)benzenes react with anions of cumyl hydroperoxide in the presence of t-BuOK in liquid ammonia to form nitro-(pentafluorosulfanyl)phenols. Their reduction with hydrogen in the presence of Raney-Nickel provides amin

Full text of DOI:10.1016/j.tetlet.2011.06.011

Tetrahedron Letters 52 (2011) 4392–4394
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hydroxylation of nitro-(pentafluorosulfanyl)benzenes via vicarious
nucleophilic substitution of hydrogen
⇑
Petr Beier , Tereza Past y´ rˇ íková
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Para- and meta-nitro-(pentafluorosulfanyl)benzenes react with anions of cumyl hydroperoxide in the
presence of t-BuOK in liquid ammonia to form nitro-(pentafluorosulfanyl)phenols. Their reduction with
hydrogen in the presence of Raney-Nickel provides amino-(pentafluorosulfanyl)phenols.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 4 April 2011
Revised 24 May 2011
Accepted 3 June 2011
Available online 13 June 2011
Keywords:
Pentafluorosulfanyl group
Vicarious nucleophilic substitution
Hydroxylation
The interest of the life science and material industries in novel
fluorine-containing substituents is nowadays prevalent. One of
such fluorine-containing groups which has gained considerable
attention recently, mainly by the crop science and liquid crystal
reported with the exception of S
halo-nitro-(pentafluorosulfanyl)benzenes.
reactions of compounds 1 that give SF -benzene derivatives start
N
Ar reactions of the halogen of
5
Thus, all known
5
from reduction of the nitro group to give the corresponding
(pentafluorosulfanyl)anilines, and are followed by acylation,
5 5
industries, is the pentafluorosulfanyl (SF group
) group.1 The SF
1
d,e,2b,3b
imparts an unusual combination of properties to organic com-
pounds such as high lipophilicity, strong electron-withdrawing
character, and high thermal and hydrolytic stability. However,
the lack of good synthetic routes for the preparation of these
compounds and the inaccessibility of basic building blocks are
currently the main constraints to the exploration of the chemistry
electrophilic halogenation, or diazotization.
realized the potential of nucleophilic aromatic substitution of 1
and reported S Ar reactions of the nitro group with alkoxides
and thiolates to generate SF
Recently, we
N
6
5
aryl ethers and sulfides, and vicari-
ous nucleophilic substitution (VNS) of hydrogen with carbon
pronucleophiles to give substituted nitro-(pentafluorosulfa-
7
and development of applications of compounds with the SF
5
group.
nyl)benzenes (Scheme 1).
There has been relatively slow development in aromatic sulfur
pentafluoride chemistry, despite the fact that (pentafluorosulfa-
nyl)benzenes were first prepared more than 50 years ago.
In VNS reactions, an aromatic hydrogen of an electron-deficient
aromatic or heteroaromatic system is substituted for the nucleo-
phile, with concomitant departure of the leaving group at the
nucleophilic centre. VNS reactions have been studied mainly on
nitrobenzene derivatives and represent a good method for the
introduction of carbon, oxygen and nitrogen functional groups
2
Currently, there are two main synthetic procedures available for
SF
is based on direct fluorination of para- or meta-substituted
bis(nitrophenyl)disulfides with providing 1-nitro-4-(penta-
5
-benzenes both starting from diaryl disulfides. The first method
8
F
2
onto aromatic systems. As an extension of our investigation of
fluorosulfanyl)benzene (1a) and 1-nitro-3-(pentafluorosulfa-
nyl)benzene (1b). The second method is based on a two-step
nucleophilic aromatic displacement chemistry of compounds 1
we have studied their hydroxylation via VNS, which should pro-
vide previously unknown nitro-(pentafluorosulfanyl)phenols (2).
3
conversion of diaryl disulfides into (pentafluorosulfanyl)ben-
4
À
zenes. Synthetic transformations of nitro-(pentafluorosulfa-
Anions of alkyl hydroperoxides (ROO ) contain a leaving group
nyl)benzenes are rather limited. The presence of strongly
electron-withdrawing groups has prevented the exploration of
electrophilic aromatic substitution. Also, nucleophilic aromatic
substitution of nitro-(pentafluorosulfanyl)benzenes has not been
(RO) at the nucleophilic oxygen anion, and have been shown to un-
dergo hydroxylation of nitroarenes via VNS reactions. Due to the
rather low nucleophilicity of alkyl hydroperoxide anions the reac-
tion requires electron-deficient nitroarenes such as 3-chloronitro-
benzene or 2,4-dinitrochlorobenzene to obtain good yields of
nitrophenols. Potassium hydroxide or tert-butoxide was used as
the base and the reactions were conducted in DMF, or preferably
⇑
Corresponding author.
E-mail address: beier@uochb.cas.cz (P. Beier).
9
in liquid ammonia.
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.011

P. Beier, T. Past y´ rˇ íková / Tetrahedron Letters 52 (2011) 4392–4394
4393
YR1
NO2
X
NO2
1
2
R2
R 3E WG
R YM
1. R
EWG,
t-BuOK, low temp.
3
rt
2. R X, rt
F S
F S
5
F5S
5
1
R1 = alkyl, aryl
Y = O, S
R2 = H, alkyl, Cl, Br
EWG = Cl, Br, SO Ph, CN, CO R, P(O)(OR)
2
2
2
M = Na, K
X = Cl, Br, I, OPh
3
R
= H, alkyl, allyl, Bn
N
Scheme 1. S Ar and VNS reactions of 1.
7
group. Addition of the carbon nucleophile does not take place be-
tween the nitro and SF groups probably due to steric reasons.
5
NO2
SF5
NO2
OH
However, in this case, we did not isolate the minor isomer of the
hydroxylation reaction and so were unable to prove the structure
as 2c or 2d. Compound 2b was isolated from the mixture in 59%
PhC(CH ) OOH (1.1 equiv)
3
2
t
-BuOK (3 equiv), NH , -50 °C, 15 min
3
1
1
SF5
yield (Scheme 3). Changing the base to powdered KOH (3 equiv)
in either liquid ammonia (À50 °C, 1 h) or DMF (À50 °C, 25 min) did
not give any compound 2b or 2c; we observed only unreacted 1b in
the reaction mixture. These observations are in contrast to the re-
sults reported by Makosza and co-workers on the hydroxylation of
1a
2
a (76%)
Scheme 2. Hydroxylation of 1a.
3
meta-substituted nitrobenzenes. They identified KOH/NH as the
system giving the best yields and observed complete regioselectiv-
We performed the addition of a mixture of 1a and cumene
hydroperoxide (80% technical, 1.1 equiv) in DMF to a solution of
t-BuOK (3 equiv) in DMF at À50 °C. Termination of the reaction
by addition of aqueous HCl (1 M) after 15 min provided the ex-
pected hydroxylation product 2-nitro-5-(pentafluorosulfanyl)phe-
nol (2a) in 28% isolated yield. When liquid ammonia was used as
the reaction medium under otherwise identical conditions 2a
was isolated in 76% yield (Scheme 2).10 Increasing the reaction
temperature to reflux (À33 °C) and/or increasing the reaction time
to 30 min provided 2a in yields of around 70%.
ity for hydroxylation at the para-position relative to the nitro
9
group. The phenol derivatives 2a and 2b are new compounds
and they have been fully characterized by spectroscopic methods.
Amino-(pentafluorosulfanyl)phenols, 3 were synthesized con-
veniently from nitro-(pentafluorosulfanyl)phenols 2 by catalytic
hydrogenation with hydrogen in the presence of Raney-Nickel.
Aminophenols 3 are also new compounds and were isolated in
1
2
good to high yields (Scheme 4).
In summary, in the present work, the hydroxylation of para- and
meta-nitro-(pentafluorosulfanyl)benzenes 1a and 1b via vicarious
nucleophilic substitutions of hydrogen with cumene hydroperox-
ide in the presence of excess potassium tert-butoxide in liquid
ammonia has provided novel nitro-(pentafluorosulfanyl)phenols
2a and 2b, respectively, in good to high yields. High regioselectivity
was observed for the VNS hydroxylation of 1b. Reduction of the ni-
tro groups of 2a and 2b with hydrogen in the presence of Raney-
Nickel gave novel aminophenols 3a and 3b, respectively, in good
to high yields. These four new phenol derivatives 2 and 3 can be
Similar hydroxylation conditions were applied to the meta-iso-
mer 1b. Reaction of 1b, cumene hydroperoxide and an excess of t-
BuOK in liquid ammonia at À40 to À33 °C for 15 min gave a mix-
ture of 2-nitro-4-(pentafluorosulfanyl)phenol (2b) and its isomer
[
probably 4-nitro-2-(pentafluorosulfanyl)phenol (2c)] in a 95:5 ra-
tio as determined by GC/MS analysis. Our investigations on the
VNS reactions of 1b with carbon pronucleophiles showed that
the nucleophile adds preferentially at the ortho-position relative
to the nitro group (para- to the SF group); the minor isomer con-
5
tained the substituent at the para-position relative to the nitro
utilized as basic building blocks for the synthesis of SF -benzenes.
5
NO2
NO2
NO2
NO2
OH
HO
PhC(CH ) OOH (1.1 equiv)
3
2
+
+
t
-BuOK (3 equiv), NH , -40 °C to -33 °C, 15 min
3
F S
F S
F S
5
5
F5S
5
OH
1
b
2b (59%)
b:2c:2d =95:5:0
2d
2
c
2
Scheme 3. Hydroxylation of 1b.
NO2
NH2
OH
OH
H , Ra-Ni
EtOH, rt, 3 h
Y1
Y2
H
SF5
2
2
3 Yield
3a 81%
3b 72%
Y2
Y2
2a SF5
2b
Y1
Y1
H
2
3
Scheme 4. Nitro group reduction of nitrophenols 2.

4
394
P. Beier, T. Past y´ rˇ íková / Tetrahedron Letters 52 (2011) 4392–4394
For example, further derivatization may exploit the nucleophilic
character of the hydroxy or amino groups, diazotization of the ami-
no group (and follow-up reactions), or electrophilic aromatic sub-
stitution chemistry of compounds 3.
10. Experimental procedure: To a stirred solution of t-BuOK (337 mg, 3 mmol) in
liquid NH
(ca. 5 mL) at À40 °C was added dropwise a solution of 1 (249 mg,
mmol) and cumene hydroperoxide (80%, 203 L, 1.1 mmol) in dry THF
1 mL). The resulting brown mixture was stirred at À50 °C (for 1a) or À40 to
À33 °C (for 1b) for 15 min followed by the addition of solid NH Cl and
evaporation of NH . The resulting mixture was treated with HCl (1 M) to pH 0
and extracted with CH Cl
(3 Â 20 mL). The combined organic extracts were
washed with NaOH (0.5 M, 3 Â 15 mL), the alkaline solution was acidified with
HCl (6 M) to pH 0 and then extracted with CH Cl
(3 Â 20 mL). The combined
organic phase was dried (MgSO ) and evaporated. Column chromatography
SiO , hexane/EtOAc) gave products 2.
3
1
(
l
4
3
2
2
Acknowledgement
2
2
4
Support of this work by the Academy of Sciences of the Czech
(
2
Republic
(Research
Plan
AVZ40550506)
is
gratefully
Compound 2a (201 mg, 76%) pale yellow liquid; R
f
0.38 (hexane/EtOAc, 97:3);
À1
acknowledged.
m
max/cm (neat) 3275, 3120, 3077, 1625, 1591, 1540, 1476, 1443, 1318, 1262,
1
238, 1181, 1109, 1067, 939, 843, 809, 757; d
J = 9.3, 2.4 Hz), 7.62 (d, 1H, J = 2.4 Hz), 8.23 (d, 1H, J = 9.3 Hz), 10.56 (br s, 1H);
(100 MHz, CDCl ) 117.6 (quin, J = 4.7 Hz), 118.9 (quin, J = 4.8 Hz), 125.6,
34.6, 154.5, 158.8–159.6 (m); d (376 MHz, CDCl ) 61.3 (d, 4F, J = 150.7 Hz),
9.4–80.7 (m, 1F); m/z (EI) 265 [M] (100%), 127 (12), 99 (15), 89 (21), 83 (27),
H 3
(400 MHz, CDCl ) 7.40 (dd, 1H,
Supplementary data
d
C
3
1
7
6
F
3
+
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.06.011.
+
3 (31), 62 (14), 57 (14), 53 (17); m/z (EI) calcd for C
6
H
4
F
5
NO
3
S [M] , 264.9832;
found, 264.9829.
1
1
1. Compound 2b (156 mg, 59%) pale yellow liquid; R
f
0.28 (hexane/EtOAc, 85:15);
À1
m
1
7
max/cm (neat) 3262, 3124, 3104, 1627, 1589, 1545, 1486, 1433, 1334, 1266,
References and notes
196, 1109, 1080, 909, 834, 818; d
.97 (dd, 1H, J = 9.3, 2.7 Hz), 8.57 (d, 1H, J = 2.7 Hz), 10.79 (br s, 1H); d
) 120.5, 123.9 (quin, J = 5.0 Hz), 132.3, 134.3 (quin, J = 4.4 Hz),
44.9–145.7 (m), 156.5; d (376 MHz, CDCl ) 63.3 (d, 4F, J = 151.1 Hz), 81.1–
2.7 (m, 1F); m/z (EI) 265 [M] (100%), 246 (14), 89 (16), 83 (26), 82 (14), 63
H 3
(400 MHz, CDCl ) 7.7 (d, 1H, J = 9.3 Hz),
C
1
.
(a) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH: Weinheim, 2004. pp
46–156; (b) Winter, R. W.; Dodean, R. A.; Gard, G. L. In ACS Symposium Series,
11: Fluorine-Containing Synthons; Soloshonok, V. A., Ed.; ACS Press:
(
100 MHz, CDCl
3
1
9
1
8
F
3
+
Washington, DC, 2005; pp 87–118; (c) Kirsch, P.; Röschenthaler, G. V. In ACS
Symposium Series, 949: Current Fluoroorganic Chemistry; Soloshonok, V. A.,
Mikami, K., Yamazaki, T., Welch, J. T., Honek, J. F., Eds.; ACS Press: Washington,
DC, 2007; pp 221–243; (d) Crowley, P. J.; Mitchell, G.; Salmon, R.; Worthington,
P. A. Chimia 2004, 58, 138–142; (e) Kirsch, P.; Bremer, M.; Heckmeier, M.;
Tarumi, K. Angew. Chem., Int. Ed. 1999, 38, 1989–1992; (f) Stump, B.; Eberle, C.;
Schweizer, W. B.; Kaiser, M.; Brun, R.; Krauth-Siegel, R. L.; Lentz, D.; Diederich,
F. ChemBioChem 2009, 10, 79–83.
+
(
23), 53 (13); m/z (CI) calcd for C
6
H
5
F
5
NO
3
S [MH] , 265.9910; found, 265.9916.
2. Experimental procedure:
A suspension of Raney-Nickel (100–200 mg) was
washed with EtOH (2 Â 15 mL). A solution of 2 (150 mg, 0.57 mmol) in EtOH
20 mL) was added, a balloon filled with H was attached, and the system was
evacuated and filled with H (3 cycles). The mixture was stirred at ambient
(
2
2
temperature for 3 h, followed by filtration, washing with hot THF (5 Â 5 mL),
and the solvent evaporated to give aniline 3.
Compound 3a (108 mg, 81%) white solid; mp 142–143 °C (CHCl
3
); R
f
0.28
2
.
.
(a) Sheppard, W. A. J. Am. Chem. Soc. 1960, 82, 4751–4752; (b) Sheppard, W. A. J.
Am. Chem. Soc. 1962, 84, 3064–3072.
(a) Bowden, R. D.; Greenhall, M. P.; Moilliet, J. S.; Thomson, J. WO 9705106,
À1
(
hexane/EtOAc, 3:1);
m
max/cm (neat) 3427, 3351, 3074, 2921, 2708, 1611,
1
525, 1447, 1291, 1271, 1219, 1099, 848, 804; d
s, 2H), 6.60–6.63 (m, 1H), 7.04–7.07 (m, 2H), 9.77 (br s, 1H); d
DMSO-d ) 111.0 (quin, J = 4.4 Hz), 114.4, 117.7 (quin, J = 4.5 Hz), 140.5–141.0
m), 142.1; d (376 MHz, DMSO-d ) 67.2 (d, 4F, J = 150.4 Hz), 92.2–93.8 (m, 1F);
m/z (EI) 235 [M] (100%), 127 (51), 108 (22), 98 (22), 89 (12), 80 (24); m/z (ESI)
H
(400 MHz, DMSO-d
6
) 5.37 (br
3
C
(100 MHz,
1
997; Chem. Abstr. 1997, 126, 199340.; (b) Bowden, R. D.; Comina, P. J.;
Greenhall, M. P.; Kariuki, B. M.; Loveday, A.; Philp, D. Tetrahedron 2000, 56,
399–3408; (c) Chambers, R. D.; Spink, R. C. H. Chem. Commun. 1999, 883–884.
6
(
F
6
3
+
4
5
.
.
Umemoto, T. WO 2008/118787, 2008; Chem. Abstr. 2008, 149, 402044.
(a) Sipyagin, A. M.; Bateman, C. P.; Tan, Y.-T.; Thrasher, J. S. J. Fluorine Chem.
+
calcd for C
Compound 3b after column chromatography (SiO
f
2%) white solid; mp 103–104 °C; R 0.25 (hexane/EtOAc, 3:1); mmax/cm
6 7 5
H F NOS [MH] , 236.01623; found, 236.01630.
2
, hexane/EtOAc) (96 mg,
2
001, 112, 287–295; (b) Sipyagin, A. M.; Enshov, V. S.; Kashtanov, S. A.;
Bateman, C. P.; Mullen, B. D.; Tan, Y.-T.; Thrasher, J. S. J. Fluorine Chem. 2004,
25, 1305–1316.
À1
7
(
1
neat) 3393, 3319, 3074, 2945, 2808, 2705, 2636, 2578, 1600, 1514, 1451, 1275,
217, 1079, 937, 902, 830, 813; d (400 MHz, CDCl ) 5.15 (br s, 3H), 6.64 (d, 1H,
J = 8.7 Hz), 7.03 (dd, 1H, J = 8.7, 2.6 Hz), 7.14 (d, 1H, J = 2.6 Hz); d (100 MHz,
CDCl ) 113.9, 114.3 (quin, J = 4.6 Hz), 117.8 (quin, J = 4.8 Hz), 133.8, 146.5,
46.9 (quin, J = 17.2 Hz); d (376 MHz, CDCl ) 63.8 (d, 4F, J = 149.9 Hz), 85.5–
7.1 (m, 1F); m/z (EI) 235 [M] (100%), 127 (29), 108 (24), 98 (18), 80 (30); m/z
1
H
3
6.
7.
8.
Beier, P.; Past y´ rˇ íková, T.; Vida, N.; Iakobson, G. Org. Lett. 2011, 13, 1466–1469.
Beier, P.; Past y´ rˇ íková, T.; Iakobson, G. J. Org. Chem 2011, 76, 4781–4786.
For reviews, see: (a) Makosza, M.; Winiarski, J. Acc. Chem. Res. 1987, 20, 282–
C
3
1
8
(
F
3
2
89; (b) Makosza, M.; Wojciechowski, K. Liebigs Ann. Chem. 1997, 1803–1816;
c) Makosza, M. Chem. Soc. Rev. 2010, 39, 2855–2868.
Makosza, M.; Sienkiewicz, K. J. Org. Chem. 1998, 63, 4199–4208.
+
(
+
6 6 5
EI) calcd for C H F NOS [M] , 235.0090; found, 235.0086.
9
.