Molecular Diversity

, 15:971 | Cite as

An unexpected C–C cleavage reaction: new and mild access to o-OH and o-NH-Tos benzoic acids or benzoamides

Full-Length Paper


Catalyzed by DBU or DBN, 2-acetoxy benzofuranones and 2-acetoxy-N-Tos indolin-3-ones, were readily prepared from o-acyl phenols and o-acyl anilines, respectively, reacted with H2O or a range of amines to afford o-OH and o-NH-Tos benzoic acids or benzoamides in moderate to excellent yields.


Lieben haloform reaction Haller–Bauer reaction Benzoic acid Benzoamide 

Supplementary material

11030_2011_9329_MOESM1_ESM.pdf (1.7 mb)
ESM 1 (PDF 1695 kb)


  1. 1.
    Lszló K, Barbara C (2005) Strategic application of named reaction in organic synthfcesis. Elsevier Inc, LondonGoogle Scholar
  2. 2.
    Hamlin KE, Weston AW (2011) The Cleavage of non-enolizable ketones with sodium amide. The Haller-Bauer reaction. Org React 1–36. doi: 10.1002/0471264180.or009.01
  3. 3.
    Paquette LA, Gilday JP (1990) Carbon–carbon bond cleavage by the Haller–Bauer and related reactions: a review. Org Prep Proceed Int 22: 167–201. doi: 10.1080/00304949009458195 CrossRefGoogle Scholar
  4. 4.
    Mehta G, Venkateswaran RV (2000) Haller–Bauer reaction revisited: synthetic applications of a versatile C–C bond scission reaction. Tetrahedron 56: 1399–1422. doi: 10.1016/S0040-4020(99)00921-7 CrossRefGoogle Scholar
  5. 5.
    Ishihara K, Yano T (2004) Synthesis of carboxamides by LDA-catalyzed Haller–Bauer and Cannizzaro reactions. Org Lett 6: 1983–1986. doi: 10.1021/ol0494459 PubMedCrossRefGoogle Scholar
  6. 6.
    Wei Y, Liu J, Lin S et al (2010) Acetoacetanilides as masked isocyanates: facile and efficient synthesis of unsymmetrically substituted ureas. Org Lett 12: 4220–4223. doi: 10.1021/ol101474f PubMedCrossRefGoogle Scholar
  7. 7.
    Cao L, Ding J, Gao M et al (2009) Novel and direct transformation of methyl ketones or carbinols to primary amides by employing aqueous ammonia. Org Lett 11: 3810–3813. doi: 10.1021/ol901250c PubMedCrossRefGoogle Scholar
  8. 8.
    Cho-Schultz S, Patten MJ, Huang B et al (2009) Solution-phase parallel synthesis of Hsp90 inhibitors. J Comb Chem 11: 860–874. doi: 10.1021/cc900056d PubMedCrossRefGoogle Scholar
  9. 9.
    Li X, Hewgley B, Mulrooney CA et al (2003) Enantioselective oxidative biaryl coupling reactions catalyzed by 1,5-dizadecalin metal complexes: efficient formation of chiral functionalized BINOL derivatives. J Org Chem 68: 5500–5511. doi: 10.1021/jo0340206 PubMedCrossRefGoogle Scholar
  10. 10.
    Bader AR, Kontowicz AD (1953) Phenyl ester. J Am Chem Soc 75: 5416. doi: 10.1021/ja01117a504 CrossRefGoogle Scholar
  11. 11.
    Katritzky AR, Singh SK, Cai C et al (2006) Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxylic acids. J Org Chem 71: 3364–3374. doi: 10.1021/jo052293q PubMedCrossRefGoogle Scholar
  12. 12.
    Balduzzi G, Bigi F, Casiraghi G et al (1982) Unusual friedel-crafts reactions: synthesis of salicylanilides via ortho-aminocarbonylation of phenols with phenyl isocyanate. Synthesis 7: 879–881. doi: 10.1055/s-1982-29987 CrossRefGoogle Scholar
  13. 13.
    Fu JM, Sharp MJ, Snieckus V (1988) The directed ortho metalation connection to aryl-aryl cross coupling: a general regiospecific synthesis of phenanthrols. Tetrahedron Lett 29: 5459–5462. doi: 10.1016/S0040-4039(00)80786-8 CrossRefGoogle Scholar
  14. 14.
    Kamila S, Mukherjee C, Mondal SS et al (2003) Application of directed metallation in synthesis. Part 3. Studies in the synthesis of (±)-semivioxanthin and its analogues. Tetrahedron 59: 1339–1348. doi: 10.1016/S0040-4020(02)01599-5 CrossRefGoogle Scholar
  15. 15.
    O’Mahony G, Pitts AK (2010) Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups. Org Lett 12: 2024–2027. doi: 10.1021/ol100507n PubMedCrossRefGoogle Scholar
  16. 16.
    Surman MD, Mulvihill MJ, Miller MJ (2002) Novel, 1,4-benzodiazepines from acylnitroso-derived hetero-diels-alder cycloadducts. Org Lett 4: 139–141. doi: 10.1021/ol017036w PubMedCrossRefGoogle Scholar
  17. 17.
    Banfi L, Basso A, Guanti G et al (2007) Ugi multicomponent reaction followed by an intramolecular nucleophilic substitution: convergent multicomponent synthesis of 1-sulfonyl 1,4-diazepan-5-ones and of their benzo-fused derivatives. J Org Chem 72: 2151–2160. doi: 10.1021/jo062626z PubMedCrossRefGoogle Scholar
  18. 18.
    Peifer C, Kinkel K, Abadleh M et al (2007) From five- to six-membered rings: 3,4-diarylquinolinone as lead for novel p38MAP kinase inhibitors. J Med Chem 50: 1213–1221. doi: 10.1021/jm061097o PubMedCrossRefGoogle Scholar
  19. 19.
    Gilleron P, Wlodarczyk N, Houssin R et al (2007) Design, synthesis and biological evaluation of substituted dioxodibenzothiazepines and dibenzocycloheptanes as farnesyltransferase inhibitors. Bioorg Med Chem Lett 17: 5465–5471. doi: 10.1016/j.bmcl.2007.07.002 PubMedCrossRefGoogle Scholar
  20. 20.
    Xue H, Lu X, Zheng P et al (2010) Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile. J Med Chem 53: 1397–1401. doi: 10.1021/jm901653e PubMedCrossRefGoogle Scholar
  21. 21.
    Ma T, Liu L, Xue H et al (2008) Chemical library and structure–activity relationships of 11-demethyl-12-oxo calanolide A analogues as Anti-HIV-1 agents. J Med Chem 51: 1432–1446. doi: 10.1021/jm701405p PubMedCrossRefGoogle Scholar
  22. 22.
    Ma T, Gao Q, Chen Z et al (2008) Chemical resolution of (±)-calanolide A, (±)-cordatolide A and their demethyl analogues. Bioorg Med Chem Lett 11(18): 1079–1083. doi: 10.1016/j.bmcl.2007.12.008 CrossRefGoogle Scholar
  23. 23.
    Flavin MT, Rizzo JD, Khilevich A et al (1996) Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (±)-Calanolide A and its enantiomers. J Med Chem 39: 1303–1313. doi: 10.1021/jm950797i PubMedCrossRefGoogle Scholar
  24. 24.
    Fan R, Sun Y, Ye Y (2009) Iodine(III)-mediated tandem acetoxylation-cyclization of o-acyl phenols for the facile construction of α-acetoxy benzofuranones. Org Lett 11: 5174–5177. doi: 10.1021/ol902067x PubMedCrossRefGoogle Scholar
  25. 25.
    Sun Y, Fan R (2010) Construction of 3-oxyindoles via hypervalent iodine mediated tandem cyclization–acetoxylation of o-acyl anilines. Chem Commun 46: 6834–6836. doi: 10.1039/C0CC01911A CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Department of Pharmacology and Pharmaceutical Sciences, School of MedicineTsinghua UniversityBeijingPeople’s Republic of China

Personalised recommendations