Chemical Papers

, Volume 73, Issue 2, pp 345–353 | Cite as

FeCl2·4H2O catalyzed ritter reaction with nitriles and halohydrocarbons

  • Cheng-Liang Feng
  • Gui-Bo Yin
  • Bin Yan
  • Jun-Qing Chen
  • Min JiEmail author
Original Paper


An efficient and inexpensive synthesis of N-substituted amides from the Ritter reaction of nitriles with various halohydrocarbons catalyzed by FeCl2·4H2O is described. FeCl2·4H2O economically efficiently catalyzed the Ritter reaction under solvent-free conditions. A range of halohydrocarbons (benzyl, tert-butyl and sec-alkyl halohydrocarbons) were coupled with nitriles to provide the corresponding amides in high to excellent yields.


FeCl2·4H2Amides Nitriles Halohydrocarbons Ritter reaction 



We are grateful to Nantong City Science Foundation (No. 2015) and Science program of Jiangsu College of Engineering and Technology for financial support.

Supplementary material

11696_2018_585_MOESM1_ESM.docx (1.5 mb)
Supplementary material 1 (DOCX 1504 kb)


  1. Allen CL, Lapkin AA, William JMJ (2009) An iron-catalysed synthesis of amides from nitriles and amines. Tetrahedron Lett 50:4262–4264. CrossRefGoogle Scholar
  2. Anilkumar G, Bitterlich B, Gelalcha FG, Tse MK, Beller M (2007) An efficient biomimetic Fe-catalyzed epoxidation of olefins using hydrogen peroxide. Chem Commun 2007:289–291. CrossRefGoogle Scholar
  3. Anxionnat B, Guérinot A, Reymond S, Cossy J (2009) FeCl3-catalyzed Ritter reaction. Synthesis of amides. Tetrahedron Letters 50:3470–3473. CrossRefGoogle Scholar
  4. Barbero M, Bazzi S, Cadamuro S, Dughera S (2009) O-Benzenedisulfonimide as a reusable brønsted acid catalyst for ritter-type reactions. Eur J Org Chem 2009:430–436. CrossRefGoogle Scholar
  5. Bi NM, Ren MG, Song QH (2010) Photo-ritter reaction of arylmethyl bromides in acetonitrile. Synth Commun 40:2617–2623. CrossRefGoogle Scholar
  6. Bullock RM (2007) An iron catalyst for ketone hydrogenations under mild conditions. Angew Chem Int Ed 46:7360–7363. CrossRefGoogle Scholar
  7. Cheng H, Xiong MQ, Cheng CX, Wang HJ, Lu Q, Liu HF, Yao FB, Chen C, Verpoort F (2018) In situ generated ruthenium catalyst systems bearing diverse N—heterocyclic carbene precursors for atom—economic amide synthesis from alcohols and amines. Chem An Asian J 13:440–448CrossRefGoogle Scholar
  8. Feng CL, Chu NN, Zhang SG, Cai J, Hu HY, Ji M (2014) Solvent-free synthesis of beta-enamino ketones and esters catalysed by recyclable iron(III) triflate. Chem Pap 68:1097–1103. CrossRefGoogle Scholar
  9. Firouzabadi H, Sardarian AR, Badparva H (1994) Highly selective amidation of benzylic alcohols with nitriles—a modified Ritter reaction. Synth Commun 24:601–607. CrossRefGoogle Scholar
  10. Jefferies LR, Cook SP (2014) Alcohols as electrophiles: iron-catalyzed Ritter reaction and alcohol addition to alkynes. Tetrahedron 70:4204–4207. CrossRefGoogle Scholar
  11. Jiang DH, He T, Ma L, Wang ZY (2014) Recent developments in Ritter reaction. RSC Adv 4:64936–64946. CrossRefGoogle Scholar
  12. Kalkhambkar RG, Waters SN, Laali KK (2011) Highly efficient synthesis of amides via Ritter chemistry with ionic liquids. Tetrahedron Lett 52:867–871. CrossRefGoogle Scholar
  13. Karabulut HRF, Kacan M (2002) A new method for the synthesis of N-benzylamides. Synth Commun 32:2345–2348 10.1081/SCC-120006004 CrossRefGoogle Scholar
  14. Khusnutdinov RI, Egorova TM, Khalilov LM, Meshcheriakova ES, Dzhemilev UM (2018) Direct and stereoselective iron-catalyzed amidation of binor-S with alkyl and aryl cyanides in water. Synthesis 50:1555–1559. CrossRefGoogle Scholar
  15. Lakouraj MM, Movassagh B, Fasihi J (2000) Fe3+-montmorillonite K10: an efficient catalyst for selective amidation of alcohols with nitriles under non-aqueous condition. Synth Commun 30:821–827. CrossRefGoogle Scholar
  16. Li F, Ma J, Lu L, Bao XF, Tang WY (2015) Combination of gold and iridium catalysts for the synthesis of N-alkylated amides from nitriles and alcohols. Catal Sci Technol 5:1953–1960. CrossRefGoogle Scholar
  17. Liu C, Zhang Q, Li HB, Guo SX, Xiao B, Deng W, Liu L, He W (2016) Cu/Fe catalyzed intermolecular oxidative amination of benzylic C–H bonds. Chem Eur J 22:6208–6212. CrossRefGoogle Scholar
  18. Mukhopadhyay M, Reddy MM, Maikap GC, Iqbal J (1995) Cobalt(II)-catalyzed conversion of allylic alcohols/acetates to allylic amides in the presence of nitriles. J Org Chem 60:2670–2676. CrossRefGoogle Scholar
  19. Nakanishi M, Bolm C (2007) Iron-catalyzed benzylic oxidation with aqueous tert-butyl hydroperoxide. Adv Synth Catal 349:861–864. CrossRefGoogle Scholar
  20. Olah GA, Gupta BGBJ, Narang AC (1979) Synthetic methods and reactions; nitrosonium ion induced preparation of amides from alkyl (arylalkyl) halides with nitriles, a mild and selective ritter-type reaction. Synthesis 1979:274–276. CrossRefGoogle Scholar
  21. Prosser AR, Banning JE, Rubina M, Rubin M (2010) Formal nucleophilic substitution of bromocyclopropanes with amides en route to conformationally constrained β-amino acid derivatives. Org Lett 12:3968–3971. CrossRefGoogle Scholar
  22. Qu GR, Song YW, Niu HY, Guo HM, John SF (2012) Cu(OTf)2-catalysed ritter reaction: efficient synthesis of amides from nitriles and halohydrocarbons in water. RSC Advances 2:6161–6163. CrossRefGoogle Scholar
  23. Sanz R, Martínez A, Guilarte V, Álvarez-Gutiérrez JM, Rodríguez F (2007) The ritter reaction under truly catalytic brønsted acid conditions. Eur J Org Chem 2007:4642–4645. CrossRefGoogle Scholar
  24. Theerthagiri P, Lalitha A, Arunachalam PN (2010) Iodine-catalyzed one-pot synthesis of amides from nitriles via ritter reaction. Tetrahedron Lett 51:2813–2819. CrossRefGoogle Scholar
  25. Tu YL, Yuan L, Wang T, Wang CL, Ke JM, Zhao JF (2017) Palladium-catalyzed oxidative carbonylation of aryl hydrazines with CO and O2 at atmospheric pressure. J Org Chem 82:4970–4976. CrossRefGoogle Scholar
  26. Yamato T, Hu JY, Shinoda N (2007) Perfluorinated sulfonic acid resin (Nafion-H) catalysed Ritter reaction of benzyl alcohols. J Chem Res 2007:641–643. CrossRefGoogle Scholar
  27. Zhang GS, Liu QF, Shi L, Wang JX (2008) Ferric sulfate hydrate-catalyzed O-glycosylation using glycals with or without microwave irradiation. Tetrahedron 64:339–344. CrossRefGoogle Scholar
  28. Zhao XN, Hu CH, Zhang FJ, Zhang ZH (2014) Magnetic CoFe2O4 nanoparticle immobilized N-propyl diethylenetriamine sulfamic acid as an efficient and recyclable catalyst for the synthesis of amides via the Ritter reaction. Appl Catal A 482:258–265. CrossRefGoogle Scholar
  29. Ziarani GM, Badiei A, Dashtianeh Z, Gholamzadeh P, Mohtasham NH (2013) Application of SiO2–Pr–SO3H as an efficient catalyst in the Ritter reaction. Res Chem Intermed 39:3157–3163. CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Institute of Pharmaceutical EngineeringJiangsu College of Engineering and TechnologyNantongPeople’s Republic of China
  2. 2.School of Biological Sciences & Medical EngineeringSoutheast UniversityNanjingPeople’s Republic of China

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