Synlett 2004(15): 2838-2839  
DOI: 10.1055/s-2004-836028
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Oxalic Acid: A Very Useful Brønsted Acid in Organic Synthesis

Kovuru Gopalaiah*
Department of Organic Chemistry, Indian Institute of Science, ­Bangalore - 560012, India
e-Mail: gopal@students.orgchem.iisc.ernet.in;

Further Information

Publication History

Publication Date:
25 November 2004 (online)

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 

    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