Oxalic Acid: A Very Useful Brønsted Acid in Organic Synthesis

Biographical Sketches

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 Beckmann reaction - a variety of ketoximes converted into the corresponding secondary amides by classical anti-periplanar migration upon ­heating to ca. 100 °C, and aldoximes affords 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.
(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]
(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]
(G) Oxalic acid has been used to perform selective protodestan­nylation and protodesilylation of dihydropyridine compounds. [15]
(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]

References

1 Chandrasekhar S. Gopalaiah K. Tetrahedron Lett.  2003,  44:  7437 

2a Andersen NH. Uh H.-S. Synth. Commun.  1973,  3:  125 

2b Smith AB. Empfield JR. Vaccaro HA. Tetrahedron Lett.  1989,  30:  7325 

2c Caine D. Venkataramu SD. Kois A. J. Org. Chem.  1992,  57:  2960 

2d Ziegler FE. Becker MR. J. Org. Chem.  1990,  55:  2800 

3a Pearson WH. Poon Y.-F. Tetrahedron Lett.  1989,  30:  6661 

3b Mitani K. Yoshida T. Morikawa K. Iwanaga Y. Koshinaka E. Kato H. Ito Y. Chem. Pharm. Bull.  1988,  36:  367 

3c Huet F. Lechevallier A. Pellet M. Conia JM. Synthesis  1978,  63 

4a Martin VA. Murray DH. Pratt NE. Zhao Y.-b. Albizati KF. J. Am. Chem. Soc.  1990,  112:  6965 

4b Avery MA. Chong WKM. Detre G. Tetrahedron Lett.  1990,  31:  1799 

5a Apparao S. Schmidt RR. Synthesis  1987,  896 

5b Liu H.-J. Nyangulu JM. Synth. Commun.  1989,  19:  3407 

6 Fieser LF. J. Am. Chem. Soc.  1939,  61:  3467 

7 Paquette LA. Wang T.-Z. Vo NH. J. Am. Chem. Soc.  1993,  115:  1676 

8 Peesapati V. Pauson PL. Pethrick RA. J. Chem. Res., Synop.  1987,  194 

9 Eweiss NF. Bahajaj AA. J. Heterocycl. Chem.  1987,  24:  1173 

10a Krishnamurty KV. Harris GM. Chem. Rev.  1961,  61:  213 

10b Kim D.-J. Kroeger DM. J. Mater. Sci.  1993,  28:  4744 

11a Burn D. Petrow V. J. Chem. Soc.  1962,  364 

11b Weinstein B. Fenselau AH. J. Org. Chem.  1965,  30:  3209 

12 Boeckman RK. Walters MA. Koyano H. Tetrahedron Lett.  1989,  30:  4787 

13a Demyttenaere J. Syngel KV. Markusse AP. Vervisch S. Debenedetti S. Kimpe ND. Tetrahedron  2002,  58:  2163 

13b Carlin RB. Constantine DA. J. Am. Chem. Soc.  1947,  69:  50 

13c Miller RE. Nord FF. J. Org. Chem.  1950,  15:  89 

14a Bartlett PA. Meadows JD. Ottow E. J. Am. Chem. Soc.  1984,  106:  5304 

14b Lygo B. O’Connor N. Tetrahedron Lett.  1987,  28:  3597 

15a Comins DL. Abdullah AH. Mantlo NB. Tetrahedron Lett.  1984,  25:  4867 

15b Comins DL. Hong H. J. Am. Chem. Soc.  1991,  113:  6672 

16 Giles M. Hadley MS. Gallagher T. J. Chem. Soc., Chem. Commun.  1990,  1047