DMD Oxidation of in-Situ-Generated σH Adducts Derived from Nitroarenes and the Carbanion of 2-Phenylpropionitrile to Phenols: The First Direct Substitution of a Nitro by a Hydroxy Group

Article abstract of DOI:10.1021/jo980173v

The dimethyldioxirane (DMD) oxidation of σ^H adducts derived from nitroarenes and the carbanion of 2-phenyIpropionitrile yields unexpectedly the phenols 5 as the major products, while the usually observed nitroarenes 4 are formed in very little

Full text of DOI:10.1021/jo980173v

4390
J . Org. Chem. 1998, 63, 4390-4391
DMD Oxid a tion of in -Situ -Gen er a ted σH Ad d u cts Der ived fr om
Nitr oa r en es a n d th e Ca r ba n ion of 2-P h en ylp r op ion itr ile to
P h en ols: Th e F ir st Dir ect Su bstitu tion of a Nitr o by
a Hyd r oxy Gr ou p
Waldemar Adam,*,† Mieczysław Ma¸kosza,*,‡ Krzysztof Stalin´ski,‡ and Cong-Gui Zhao†
Institute of Organic Chemistry, University of Wu¨rzburg, D-97074 Wu¨rzburg, Germany, and Institute of
Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/ 52, 01-224 Warsaw, Poland
Received February 2, 1998
The dimethyldioxirane (DMD) oxidation of σH adducts derived from nitroarenes and the carbanion
of 2-phenylpropionitrile yields unexpectedly the phenols 5 as the major products, while the usually
observed nitroarenes 4 are formed in very little amounts, if any. The phenol yield was much
improved when a small quantity (0.5-1.0 equiv.) of water was added at the start of the reaction.
This novel oxidation of Meisenheimer complexes provides the first direct synthesis of phenols from
nitroarenes, an unprecendented transformation.
Nucleophilic reagents react with nitroarenes in a
group. Some substitutents, however, hinder or totally
inhibit the oxidation. For example, the σH adduct 3b
derived from 3,5-dichloronitrobenzene (2b) is not oxidized
by KMnO4, and upon hydrolysis with aqueous NH4Cl
in liquid ammonia, both 1 and 2b are recovered es-
sentially quantitatively.3
Since anionic σH adducts 3 can be regarded as cyclo-
hexadienenitronate anions, application of other strong
carbanion-oxidizing agents was of interest. Among the
strong oxidants used for the oxidation of carbanions,
enolate anions, and related species, of particular interest
is dimethyldioxirane (DMD), one of the most powerful
and convenient oxygen-transfer agents.4 Isolated DMD
is readily available5 as an acetone solution (ca. 0.1 M)
and has been extensively employed for the oxidation of
a variety of enolates to afford R-hydroxy ketones, esters,
etc., a process of significant practical value.6
variety of ways. The initial step of these reaction is
usually reversible addition in the unsubstituted ortho
and para positions to result in the anionic σH adducts
(Meisenheimer complexes).1 These σH adducts may be
converted into products of hydrogen-atom replacement
in several ways; the most important are oxidation and
vicarious nucleophilic substitution.2 For example, re-
cently we have shown3 that the carbanion of 2-phenyl-
propionitrile (1) adds quantitatively to nitrobenzenes 2
in liquid ammonia to give σH adducts 3, which at -70 °C
are relatively long-lived intermediates. Treatment of the
σH adducts with KMnO4 leads to rapid oxidation to give
the so-called ONSH (oxidative nucleophilic substitution
of hydrogen) products 4, as shown in eq 1.3
Since DMD cannot be employed in liquid ammonia, the
σH adducts were produced and oxidized with DMD in a
1:20 DMF/THF mixture at -70 °C. The results are
summarized in Table 1. In the first experiment (Table
1, entry 1), to a solution of the σH adduct 3a of nitroben-
zene (2a ) and the carbanion of 1, a solution of DMD in
acetone was added in slight excess. After standard
workup, ca. 50% of the nitrobenzene (2a ) and the nitrile
(1) were converted to afford 6% of the ONSH product 4a
and 47% of the phenol 2-(4-hydroxyphenyl)-2-phenylpro-
This ONSH reaction proceeds selectively in the position
para to the nitro group, and the nitroarenes may possess
a variety of substituents ortho and meta to the nitro
(4) For reviews see: (a) Adam, W.; Curci, R.; Edwards, J . O. Acc.
Chem. Res. 1989, 22, 205-211. (b) Murray, R. W. Chem. Rev. 1989,
89, 1187-1201. (c) Curci, R. In Advances in Oxygenated Process;
Baumstark, A. L., Ed.; J AI: Greenwich, CT, 1990; Vol. 2, Chapter I,
pp 1-59. (d) Adam, W.; Hadjiarapoglou, L. P.; Curci, R.; Mello, R. In
Organic Peroxides; Endo, W., Ed.; Wiley: New York, 1992; Chapter 4,
pp 195-219. (e) Curci, R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem.
1995, 67, 811-822. (f) Adam, W.; Smerz, A. K. Bull. Soc. Chim. Belg.
1996, 105, 581-599. (g) Adam, W.; Smerz, A. K.; Zhao, C.-G. J . Prakt.
Chem. 1997, 339, 298-300.
* To whom correspondence should be addressed. (W.A.) Fax: +49-
931-8884756. E-mail: Adam@chemie.uni-wuerzburg.de. (M.M.)
Fax: +22-632 66 81.
† University of Wu¨rzburg.
‡ Polish Academy of Sciences.
(1) (a) Ma¸kosza, M. Pol. J . Chem. 1992, 66, 3. (b) Ma¸kosza, M. Russ.
Chem. Bull. 1996, 45, 491. (c) Terrier, F. Nucleophilic Aromatic
Displacement; VCH: Weinheim, 1991.
(2) (a) Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.
Nucleophilic Aromatic Substitution of Hydrogen; Academic Press: San
Diego, 1994. (b) Ma¸kosza, M.; Winiarski, J . Acc. Chem. Res. 1987, 20,
282-289. (c) Ma¸kosza, M.; Wojcierchowski, K. Liebigs Ann. Chem.
1997, 1805-1816.
(3) (a) Ma¸kosza, M.; Stalin´ski, K.; Kle¸pka, C. Chem. Commun. 1996,
837-838. (b) Ma¸kosza, M.; Stalin´ski, K. Chem. Eur. J . 1997, 3, 2025-
2031.
(5) (a) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847-
2853. (b) Adam, W.; Bialas, J .; Hadjiarapoglou, L. P. Chem. Ber. 1991,
124, 2337.
(6) (a) Adam, W.; Prechtl, F. Chem. Ber. 1991, 124, 2369-2372. (b)
Adam, W.; Mu¨ller, M.; Prechtl, F. J . Org. Chem. 1994, 59, 2358-2364.
(c) Guertin, K. R.; Chan, T.-H. Tetrahedron Lett. 1991, 32, 715-718.
(d) Adam, W.; Korb, M. Tetrahedron 1996, 52, 5487-5494.
S0022-3263(98)00173-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/30/1998

Direct Oxidation of Nitroarenes to Phenols
J . Org. Chem., Vol. 63, No. 13, 1998 4391
Ta ble 1. DMD Oxid a tion of σH Ad d u ctsa
Similar results were obtained with nitroarene 5b (Table
1, entries 7 and 8).
The difference between entries 1 and 5 (Table 1) is that
in the former, aq NH4Cl (pH ca. 5) was used in the
workup, which suggests that acidic conditions disfavor
the oxidation to achieve high yields of phenol 5a . Indeed,
when 1 equiv of 2 N NaOH solution was employed in the
workup instead of aq NH4Cl, again a good yield (70%) of
phenol 5a was obtained (Table 1, entry 6). This suggests
that the oxidation occurs, at least partially, upon addition
of water. Similarly, when σH adducts 3c, 3d , and 3e,
derived from nitroarenes 2c, 2d , and 2e, were treated
with DMD and subsequently worked up with water, the
corresponding phenols were obtained in 72, 81, and 87%
yields (Table 1, entries 9, 10, and 11). Moreover, all the
nitroarenes 2 studied here gave the phenolic products 5
as the major products, while only small amounts, if any,
of the ONSH products 4 were detected (Table 1).
Mechanistically, this unprecedented oxidation of σH
adducts by DMD is akin to the Nef reaction.7 For
example, the formation of 4,4-disubstituted cyclohexadi-
enones was already observed when para σH adducts of
MeMgBr or BuMgBr to p-nitrotoluene were acidified with
aqueous HCl.8 Similarly, the addition of an alkylmagne-
sium halide to 10-alkyl-9-nitroanthracene and oxidation
of the resulting σH adducts by Pb(OCOCH3)4 gave 10,10-
dialkylanthrones.9 Although the normal Nef reaction is
a hydrolysis, the present case (Table 1) is an oxidation
process because DMD is essential. For instance, acidi-
fication of the σH adduct 3a with 27% aqueous HCl led
only to the corresponding nitroso compound. An attempt
to oxidize 3a by 70% H2O2 resulted in its reversion to
the starting materials. It is most likely that the phenols
arise from the corresponding dienenones, but the details
of the oxidation mechanism by DMD require a more
elaborate scrutiny.
a
With 1.0 mmol of 1, 1.0 mmol of 2, 1.1 mmol of t-BuOK, and
1.2 mmol of DMD in DMF/THF (1 mL/20 mL) under argon gas
unless otherwise indicated. DMD solution (predried two times
over fresh molecular sieves for 2 days each), precooled at -70 °C
b
and added in one portion.
Yields of isolated materials after
column chromatography on silica gel. c DMD solution dried over
d
P2O5 (3 h) and K2CO3 (2 h). H2O was added first to the DMD
solution and the wet solution to the reaction mixture. e H2O was
added first to the reaction mixture and 5 min later the dry DMD
solution. f DMD was added first to the reaction mixture and 5
g
min later the H2O. aqueous 2 N NaOH solution added.
In conclusion, the DMD oxidation of σH adducts,
generated in situ from the 2-phenylpropionitrile carban-
ion and nitroarenes gives the corresponding phenols 5
in very good yields. This unprecedented oxidation pro-
vides the first direct way to prepare phenols from
nitroarenes.
Ack n ow led gm en t . Generous financial support of
the Deutsche Forschungsgemeinschaft (Schwerpunkt-
programm: Peroxidchemie) and the Fonds der Chemis-
chen Industrie is gratefully appreciated. M. Ma¸kosza
thanks the Alexander von Humboldt Foundation for a
research award, which made this collaboration possible,
and C.-G. Zhao is grateful to the DAAD (Deutscher
Akademischer Austauschdienst) for a doctoral fellow-
ship.
pionitrile (5a ). This unexpected reaction offers the first
direct method for the synthesis of phenols from nitro-
arenes.
Since the conversion of the σH adduct into phenol was
only around 50%, the reaction was studied in detail to
optimize the yield of the phenol 5a . In view of the fact
that DMD solutions dried over molecular sieves contain
traces of water, presumably the σH adduct 3 was hydro-
lyzed back to the starting materials. Therefore, to
exclude this possiblity, the DMD solution was rigorously
dried over P2O5 and subsequently over solid K2CO3, the
latter to remove possible traces of acids. Surprisingly,
with such a rigorously dried DMD solution, only traces
of the phenol 5a were formed (Table 1, entry 2). Con-
sequently, water (0.5 equiv relative to 2) was intention-
ally added to the DMD solution, and a much better yield
(71%) of the phenol 5a was obtained (Table 1, entry 3).
In fact, water may be added separately, either before or
after the oxidation by DMD, to produce the phenol 5a in
good yields, i.e., 77% (Table 1, entry 4) before the addition
of the DMD solution and 83% (Table 1, entry 5) after.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for the DMD oxidation of σH adducts 3 and the data for
the characterization of the phenols 5 (5 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O980173V
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