Novel Transformation of Primary Nitroalkanes and Primary Alkyl Bromides to the Corresponding Carboxylic Acids

Full text of DOI:10.1021/jo962110n

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34
J . Org. Chem. 1997, 62, 234-235
Novel Tr a n sfor m a tion of P r im a r y
Sch em e 1
Nitr oa lk a n es a n d P r im a r y Alk yl Br om id es
to th e Cor r esp on d in g Ca r boxylic Acid s
†
Christophe Matt, Alain Wagner, and
,
‡
Charles Mioskowski*
Laboratoire de Synth e` se Bioorganique, Universit e´ Louis
Pasteur de Strasbourg, Unit e´ associ e´ e au CNRS,
Facult e´ de pharmacie, 74 route du Rhin-BP 24-F-67401
Illkirch-Graffenstaden, France
Sch em e 2
Received November 12, 1996
Nitro compounds are very potent intermediates in
1
organic synthesis. However, there are strikingly few
examples of naturally occuring aliphatic nitro compounds
or of synthetic products that have found significant
biological use. For this reason, the transformation of
nitro compounds into other functionalities is crucial. The
2
quantitatively led to the corresponding carboxylic acid.8
It is known that primary bromides and primary mesy-
lates can be converted to the corresponding nitro com-
conversion to aldehydes (the Nef reaction) and the
reduction to the amine3 appear to be the most useful
transformations of primary nitroalkanes.
1
The oxidation of primary nitro compounds to carboxylic
acids is rarely useful. This transformation is generally
pounds by the action of sodium nitrite in DMSO.
However, in the presence of acetic acid and excess sodium
nitrite, the nitro derivative was not isolated and the
reaction directly gave the carboxylic acid in 85% yield.
The formation of a small amount of alcohol was also
observed, and is presumably due to the hydrolysis of the
unavoidable nitrite compound, a byproduct arising from
the O-alkylation of sodium nitrite. This reaction is, to
our knowledge, the only synthetically useful one-pot
oxidation of primary bromides to the corresponding
carboxylic acids. To account for this transformation we
propose a mechanism analogous to that described when
the reaction is carried out under strongly acidic condi-
4
carried out in strongly acidic, aqueous media or by using
5
6
strong oxidants such as permanganate or molybdate.
7
In 1956, Kornblum et al. reported the oxidation of
nitroparaffins using a mixture of nitrite ester and sodium
nitrite. However, the reaction was prone to poor yields
(between 9 and 52%) and long reaction times. The
reaction was postulated to proceed via the formation of
a nitrolic acid, which reportedly is highly unstable.
Nitrite ester was thought to act as an electrophilic
nitrosonium ion equivalent and sodium nitrite as a base.
This lack of mechanistic undersanding as well as poor
yields prevented this reaction from any significant ap-
plication.
Forty years later, we report a very efficient related
reaction using a mixture of sodium nitrite and acetic acid
in DMSO (Scheme 1). Investigation of the mechanism
enabled us to prove that nitrolic acids are stable and
easily accessible compounds.
9
tions (Scheme 2).
Under acidic conditions the nitroalkane is in equilib-
rium with the aci form A that reacts with a nitrosating
agent to form the corresponding nitrolic acid B. The
further transformation of the nitrolic acid B into the
hydroxamic acid D proceeds via the formation of a
reactive nitrile oxide intermediate C. By nucleophilic
attack of sodium nitrite, C is converted into D, which is
readily hydrolyzed to yield the carboxylic acid.
The treatment of 2-phenylnitroethane with sodium
nitrite and acetic acid in dimethyl sulfoxide at 35 °C
To prove that under our conditions the reaction pro-
ceeds via the same intermediate, we intercepted or
isolated several of these intermediates.
†
Phone: (33) 3 88 67 68 63. Fax: (33) 3 88 67 88 91. E-mail:
alwag@aspirine.u-strasbg.fr.
‡
E-mail: mioskow@aspirine.u-strasbg.fr.
1) Larson, J . H. The Chemistry of Nitro and Nitroso Groups,
1
0
(
Nitrolic acids were first reported by Meyer in 1873
but have, apparently, fallen into disuse.11 This might be
due to the lack of a reliable preparative method and to
the conviction that these are unstable compounds. The
nitrolic acid intermediates B were isolated12 simply by
carrying out the reaction at 18 °C instead of 35 °C
Methods of Formation of Nitro Group in Aliphatic and Alicyclic
Systems; Pata ¨ı , S., Ed.; Interscience Publishers: New York, 1969; Part
1
1
, pp 301-348. Seebach, D.; Colwin, E. W.; Lehr, F.; Weller, T. Chimia
979, 33, 1-17. Rosini, G.; Ballini R. Synthesis 1988, 833-847.
(
2) Nef, J . V. Ann. Chem. 1899, 308, 264-333. McMurry, J . E.;
Melton, J . J . Org. Chem. 1973, 38, 4367-4373. Kornblum, N.; Brown,
R. A. J . Am. Chem. Soc. 1965, 87, 1742-1747. Kornblum, N.; Wade,
P. A. J . Org. Chem. 1973, 38, 1418-1420. Olah, G. A.; Gupta, B.
Synthesis 1980, 44-45. McMurry, J . E.; Melton, J .; Padgett, H. J . Org.
Chem. 1974, 39, 259-260. For a review of the Nef reaction, see:
Pinnick, H. W. Org. React. 1990, 38, 655-792.
(Scheme 3).
Nitrolic acids appear to be stable compounds that can
be purified by silica gel chromatography. Heating at 60
(
3) Grundmann, C.; Ruske, W. Chem. Ber. 1953, 86, 939-943.
Parham, W. E.; Ramp, F. L. J . Am. Chem. Soc. 1951, 73, 1293-1295.
Noyce, W. K.; Coleman, C. H.; Barr, J . T. J . Am. Chem. Soc. 1951, 73,
295-1296. Stilles, M.; Finkbeiner H. L. J . Am. Chem. Soc. 1959, 81,
05-506. Corey E. J .; Andersen N. H.; Carlson, R. M.; Paust, J .; Vedejs,
E.; Vlattas I.; Winter, R. E. K. J . Am. Chem. Soc. 1968, 90, 3245-
(8) Typ ica l P r oced u r e. A solution of the nitroalkane (1 mmol),
sodium nitrite (3 mmol), and acetic acid (10 mmol) in dimethyl
sulfoxide (2 mL) was stirred at 35 °C for 6 h. After acidification with
a 10% aqueous solution of hydrochloric acid, the product was extracted
several times with ether and purified by silica gel chromatography.
(9) Edward, J . T.; Tremaine, P. H. Can. J . Chem. 1971, 49, 3483-
3488. Edward, J . T.; Tremaine, P. H. Can. J . Chem. 1971, 49, 3489-
3492. Edward, J . T.; Tremaine, P. H. Can. J . Chem. 1971, 49, 3493-
3501.
(10) Meyer V. Ber. 1873, 6, 1492. Wieland, H.; Semper, L. Chem.
Ber. 1906, 39, 2522-2526.
(11) Brueer, E.; Aurich, H. G.; Nielsen, A. Nitrones, Nitronates &
Nitroxides, The chemistry of functional groups; Pata ¨ı , S., Ed.; J . Wiley
& Sons: New York, 1992.
1
5
3
247.
(
4) Cundall, R. B.; Locke, A. W. J . Chem. Soc. B 1968, 98-103.
Edward, J . T.; Tremaine, P. H. Can. J . Chem. 1971, 49, 3489-3492.
Armand, J . Bull. Soc. Chim. Fr. 1965, 3246-3255.
(
5) Saville-Stones, E. A.; Lindell, S. D. Synlett 1991, 591-592.
6) Galobardes, M. R.; Pinnick, H. W. Tetrahedron Lett. 1981, 22,
(
5
235-5338.
7) Kornblum, N.; Blackwood, R. K.; Mooberry, D. D. J . Am. Chem.
Soc. 1956, 78, 1501-1504.
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S0022-3263(96)02110-X CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 2, 1997 235
Sch em e 3
Ta ble 1.
Sch em e 4
°
C for 3 h did not lead to significant decomposition.
However, when these compounds were subjected to acetic
acid and sodium nitrite in dimethyl sulfoxide at 35 °C,
the nitrolic acids B quantitatively afforded the corre-
sponding carboxylic acids.
The mechanism for the transformation of B into the
hydroxamic acid D proceeds via the formation of a
reactive nitrile oxide intermediate C. In the presence of
an excess of 1-hexene (7 equiv), the postulated nitrile
oxide was intercepted and the isoxazole adduct was
obtained in 72% yield (Scheme 4).
Under our reaction conditions, an authentic sample of
D rapidly and quantitatively yielded the corresponding
carboxylic acid. Apparently, the solvent is not involved
in the transformation, because the reaction could be
carried out in either DMF or sulfolane (dipolar aprotic
solvents) and consistently afforded the products in excel-
lent yield.
To explain the mildness and the efficiency of this
transformation, we postulate that the reaction is not acid-
catalyzed, but propelled by an equivalent of nitrosonium
ion, generated in situ by the reaction of acetic acid with
sodium nitrite.13 To support this postulate, we subjected
all the intermediates to several reaction conditions. In
each case, the reaction proceeded only if both acetic acid
and sodium nitrite were present. Furthermore, in the
absence of acetic acid, but with 1 equiv of nitrosonium
tetrafluoroborate salt and 1.3 equiv of sodium nitrite, the
reaction proceeded readily and the carboxylic acid was
isolated in 82% yield. This demonstrates the predomi-
nant role of a nitrosonium species in the mechanism.
Several representative substrates were subjected to our
reaction conditions. The results obtained are sum-
marized in Table 1.
The reaction proceeded smoothly and the products
were obtained in over 90% yield starting from the nitro
derivatives and about 80% yield starting from the
bromides. The mildness of the reaction conditions ren-
ders it compatible with many acid- or base-sensitive
functionalities. Thus, THP ethers and benzyl esters
remained intact (Table 1, entries 3-5). Alkynes and
alkenes proved to be stable under the reaction conditions
(Table 1, entries 6 and 7), and no cycloadducts were
detected. Furthermore, even unprotected acids (Table 1,
entry 8) could be transformed. When the reaction was
carried out with an unprotected alcohol, the hydroxy acid
obtained had to be acetylated to facilitate its purification
(Table 1, entry 9).
In summary, we report a useful and new transforma-
tion of primary nitroalkanes and primary alkyl bromides
into the corresponding carboxylic acids, with very good
yield. The reaction proceeded under mild acidic condi-
tions that render it compatible with various sensitive
functionalities. This study also provided new conditions
for the conversion of primary nitro compounds into the
corresponding nitrolic acids. These transformations ap-
pear to proceed via a novel mechanism that involves the
nitrosonium ion as an active species.
(
12) Typ ica l P r oced u r e. A solution of 2-nitroethylbenzene (0.15
g, 1 mmol), sodium nitrite (0.14 g, 2 mmol), and acetic acid (0.57 mL,
0 mmol) in dimethyl sulfoxide (2 mL) was stirred at 18 °C for 8 h.
1
The reaction mixture was then diluted with 10 mL of a 10% aqueous
solution of hydrochloric acid. The product was extracted with ether (3
×
15 mL). The organic layers were combined, washed with a solution
of sodium carbonate, dried over MgSO , and concentrated under
vacuum. Purification by silica gel chromatography yielded 150 mg of
4
1
1
-nitro-2-phenylethanone oxime as a white solid. H NMR (200 MHz,
13
CDCl
3
) δ ppm: 10.10 (s, 1H, OH); 7.33 (s, 5H); 4.29 (s, 2H). C NMR
-1
(
50 MHz, CDCl
3
) δ ppm: 160.9, 132.5, 128.8, 127.5, 30.0. IR ν (cm ):
Ack n ow led gm en t. J . Albert Ferreira and Pierre
Held are gratefully acknowledged for reviewing this
manuscript.
3
8
1
293.6, 2890.3, 1541.9, 1496.1, 1455.6, 1421.3, 1343.0, 1075.8, 1030.7,
55.6, 736.7, 709.2. MS (CI/NH ) m/ z (rel intens): 134 (M - NO ,
3 2
+ +
+
+
00), 151 (MNH
13) Liddell, H. F.; Saville, B. Chem. Ind. 1957, 493-494. Hughes,
E. D.; Ingold, C. K.; Ridd, J . H. J . Chem. Soc. 1958, 88-98.
4
2 4
- NO , 60), 181 (MH , 16), 198 (MNH , 20).
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J O962110N