Download Spotlight 106 Oxalic Acid: A Very Useful Brønsted Acid in Organic Synthesis SYNLETT

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SYNLETT
Spotlight 106
SPOTLIGHT
Oxalic Acid: A Very Useful Brønsted
Acid in Organic Synthesis
Compiled by Kovuru Gopalaiah
This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and
preparation of the reagent in
current research
Kovuru Gopalaiah was born in Andhra Pradesh, India in 1976.
He received his Master degree in organic chemistry from Sri
Venkateswara University, Tirupati, India. In 2000 he joined the
Department of Organic Chemistry, Indian Institute of Science,
Bangalore, India for his PhD degree under the tutelage of Prof. S.
Chandrasekhar. His research interests focus on the development of
novel synthetic strategies, reaction mechanisms and study of
stereoelectronic effects in the area of amide chemistry.
Introduction
The title compound oxalic acid is available in anhydrous
and dihydrate forms and exhibits several features which
have made it particularly attractive as a reagent in organic
synthesis. Oxalic acid is a mild Brønsted acid, which finds
application in the Beckmann reaction,1 protection and
deprotection of carbonyl compounds,2–4 and various selective cleavage and hydrolytic reactions. It is frequently
used as a mild acidic quench for a variety of reactions including oxidations.5 Oxalic acid has also been used as an
acidic agent in a number of condensation processes such
as condensation of allylic alcohols with aromatic rings,6
carbonyl compounds and hydrazines,7 aromatic amines
and aldehydes,8 and it has been utilized as a bifunctional
condensation partner in the synthesis of heterocyclic systems.9
Oxalic acid is the simplest of the dicarboxylic acids and is
widely used in inorganic chemistry as a precipitant and
chelating agent (oxalate as a bidentate ligand has been of
great interest in coordination chemistry).10
Abstracts
(A) Oxalic acid is an efficient reagent for the Beckmann reaction –
a variety of ketoximes are converted into the corresponding
secondary amides by classical anti-periplanar migration upon
heating to ca. 100 °C, and aldoximes afford the corresponding
nitriles. The procedure offers high yield of the desired products,
gaseous by-products (CO + CO2) and the absence of reaction
solvent.1
(B) Anhydrous oxalic acid is an excellent mediator for one-pot
transformation of ketones to amides in the presence of
hydroxylamine hydrochloride. The method is effective for various
aromatic and aliphatic ketones, and provides excellent yield of the
products.1
(C) In the presence of aqueous oxalic acid, enol ethers undergo
expeditious hydrolysis to the corresponding ketones without concomitant migration of the double bond.11 In contrast, use of a mineral acid typically gives the conjugated ketone. This method offers
considerable advantage in terms of regioselectivity of the product.
SYNLETT 2004, No. 15, pp 2838–283907.12 04
Advanced online publication: 25.11.2004
DOI: 10.1055/s-2004-836028; Art ID: V10804ST
© Georg Thieme Verlag Stuttgart · New York
OH
N
(COOH)2
R-NH-CO-R1
80–130 °C, 3–15 h
R1
R
R,
R1 =
64–95%
aryl, alkyl
O
R
R1
+ NH2OH·HCI
(COOH)2
R-NH-CO-R1
100–110 °C, 3.5–12.5 h
60–96%
COMe
Me
COMe
Me
(COOH)2
H
MeO
H
THF–H2O
O
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Department of Organic Chemistry, Indian Institute of Science,
Bangalore – 560012, India
E-mail: [email protected]
SPOTLIGHT
O
MeO
O
O
(COOH)2, MeCN
r.t., 9 h, 86%
N3
N3
MeO
CN
(COOH)2
OEt
C (CH2)3 CH
MeO
OEt Acetone–H2O
iPr
MeO
91%
MeO
MeO
(E) Oxalic acid on SiO2 facilitates mild acidic hydrolysis of diethyl
b-dialkylamino vinylphosphonates (vinylogous phosphoramides)
to b-keto phosphonates. b-Keto phosphonates are excellent reagents for homologation of aldehydes and ketones to a,b-unsaturated aldehydes and ketones via the Wadsworth–Emmons–Horner
reaction.12
(F) Alcohols have been efficiently converted into alkenes either by
heating with anhydrous oxalic acid or refluxing in aqueous oxalic
acid.13 Appropriately inclined hydroxyl ketones have been cyclodehydrated to give cyclic ethers.14
HOCH2C(CH3)2CH2OH
N
R1
R
PO(OEt)2
EtO
Oxalic acid, SiO2, CH2Cl2
EtO
58–80%
CN
C (CH2)3-CHO
iPr
O
O
P
R1
R
R, R1 = H, alkyl, aryl, alkenyl
O
BnO
OH
Me
H
Oxalic acid
CO2Me
BnO
CH2Cl2, reflux
Me
O
CO2Me
57%
(G) Oxalic acid has been used to perform selective protodestannylation and protodesilylation of dihydropyridine compounds.15
SnMe3
Oxalic acid
N
H
O
THF–H2O
R
49–68%
R1
N
H
O
R
R1
1
R, R = alkyl, aryl
(H) Oxalic acid is an efficient reagent for the selective removal of
the ester functionality of b-keto esters to the corresponding ketone
by conventional acid hydrolysis and decarboxylation in aqueous
media.16
EtO2C
O
O
Oxalic acid
N
R
CO2Et
H2O, dioxane
100 °C
67–89%
N
R
CO2Et
R = alkyl, alkenyl, aryl
References
(1) Chandrasekhar, S.; Gopalaiah, K. Tetrahedron Lett. 2003,
44, 7437.
(2) (a) Andersen, N. H.; Uh, H.-S. Synth. Commun. 1973, 3,
125. (b) Smith, A. B. III; Empfield, J. R.; Vaccaro, H. A.
Tetrahedron Lett. 1989, 30, 7325. (c) Caine, D.;
Venkataramu, S. D.; Kois, A. J. Org. Chem. 1992, 57, 2960.
(d) Ziegler, F. E.; Becker, M. R. J. Org. Chem. 1990, 55,
2800.
(3) (a) Pearson, W. H.; Poon, Y.-F. Tetrahedron Lett. 1989, 30,
6661. (b) Mitani, K.; Yoshida, T.; Morikawa, K.; Iwanaga,
Y.; Koshinaka, E.; Kato, H.; Ito, Y. Chem. Pharm. Bull.
1988, 36, 367. (c) Huet, F.; Lechevallier, A.; Pellet, M.;
Conia, J. M. Synthesis 1978, 63.
(4) (a) Martin, V. A.; Murray, D. H.; Pratt, N. E.; Zhao, Y.-b.;
Albizati, K. F. J. Am. Chem. Soc. 1990, 112, 6965.
(b) Avery, M. A.; Chong, W. K. M.; Detre, G. Tetrahedron
Lett. 1990, 31, 1799.
(5) (a) Apparao, S.; Schmidt, R. R. Synthesis 1987, 896.
(b) Liu, H.-J.; Nyangulu, J. M. Synth. Commun. 1989, 19,
3407.
(6) Fieser, L. F. J. Am. Chem. Soc. 1939, 61, 3467.
(7) Paquette, L. A.; Wang, T.-Z.; Vo, N. H. J. Am. Chem. Soc.
1993, 115, 1676.
(8) Peesapati, V.; Pauson, P. L.; Pethrick, R. A. J. Chem. Res.,
Synop. 1987, 194.
(9) Eweiss, N. F.; Bahajaj, A. A. J. Heterocycl. Chem. 1987, 24,
1173.
(10) (a) Krishnamurty, K. V.; Harris, G. M. Chem. Rev. 1961, 61,
213. (b) Kim, D.-J.; Kroeger, D. M. J. Mater. Sci. 1993, 28,
4744.
(11) (a) Burn, D.; Petrow, V. J. Chem. Soc. 1962, 364.
(b) Weinstein, B.; Fenselau, A. H. J. Org. Chem. 1965, 30,
3209.
(12) Boeckman, R. K.; Walters, M. A.; Koyano, H. Tetrahedron
Lett. 1989, 30, 4787.
(13) (a) Demyttenaere, J.; Syngel, K. V.; Markusse, A. P.;
Vervisch, S.; Debenedetti, S.; Kimpe, N. D. Tetrahedron
2002, 58, 2163. (b) Carlin, R. B.; Constantine, D. A. J. Am.
Chem. Soc. 1947, 69, 50. (c) Miller, R. E.; Nord, F. F. J.
Org. Chem. 1950, 15, 89.
(14) (a) Bartlett, P. A.; Meadows, J. D.; Ottow, E. J. Am. Chem.
Soc. 1984, 106, 5304. (b) Lygo, B.; O’Connor, N.
Tetrahedron Lett. 1987, 28, 3597.
(15) (a) Comins, D. L.; Abdullah, A. H.; Mantlo, N. B.
Tetrahedron Lett. 1984, 25, 4867. (b) Comins, D. L.; Hong,
H. J. Am. Chem. Soc. 1991, 113, 6672.
(16) Giles, M.; Hadley, M. S.; Gallagher, T. J. Chem. Soc., Chem.
Commun. 1990, 1047.
Synlett 2004, No. 15, 2838–2839
© Thieme Stuttgart · New York
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(D) Oxalic acid has been used for both the preparation and the
cleavage of acetal and ketal functionalities. Ketones and aldehydes
react with ethylene glycol or ethanol in the presence of anhydrous
oxalic acid to provide the corresponding ketals and acetals. Cleavage of ketals and acetals to regenerate the carbonyl group has been
accomplished with the use of aqueous oxalic acid. Acid-sensitive
functionality is well tolerated under these conditions.2–4
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