DMF-Catalysed Thermal Dehydration of Aldoximes: A Convenient Access to Functionalized Aliphatic and Aromatic Nitriles

Abstract

N,N-Dimethylformamide was found to act as solvent and catalyst in the dehydration of aldoximes to nitriles. The reaction ­required heating at 135 °C and yields of nitriles were moderate to good. (Benzylideneaminooxy)formaldehyde was detected as an ­intermediate in one of the reactions.

Key words

aldoximes - dehydration - nitriles

References and Notes

• 1a Smith M. March J. Advanced Organic Chemistry: Reactions, Mechanisms and Structure   6th ed.:  Wiley Interscience; Chichester: 2007. 
• 1b Larock RC. Comprehensive Organic Transformations   2nd ed.:  Wiley; New York: 1999. 
• 1c Trost B. Flemming I. Comprehensive Organic Synthesis   Pergamon Press; Oxford: 1991. 
• 1d Katritzky AR. Meth-Cohn O. Rees CW. Comprehensive Organic Functional Group Transformations   Oxford; Pergamon: 1995. 
• 2a Romero M. Renard P. Caignard DH. Atassi G. Solans X. Constans P. Bailly C. Pujol MD. J. Med. Chem.  2007,  50:  294 
• 2b Pei ZH. Li XF. Longenecker K. von Geldern TW. Wiedemann PE. Lubben TH. Zinker BA. Stewart K. Ballaron SJ. Stashko MA. Mika AK. Beno DWA. Long M. Wells H. Kempf-Grote AJ. Madar DJ. McDermott TS. Bhagavatula L. Fickes MG. Pireh D. Solomon LR. Lake MR. Edalji R. Fry EH. Sham HL. Trevillyan JM. J. Med. Chem.  2006,  49:  3520 
• 2c Sakya SM. Hou XJ. Minich ML. Rast B. Shavnya A. DeMello KML. Cheng H. Li J. Jaynes BH. Mann DW. Petras CF. Seibel SB. Haven ML. Bioorg. Med. Chem. Lett.  2007,  17:  1076 
• 2d Iyengar BS. Dorr RT. Remers WA. J. Med. Chem.  2004,  47:  218 
• 2e Kamath S. Buolamwini JK. J. Med. Chem.  2003,  46:  4657 
• 3a Jin F. Confalone PN. Tetrahedron Lett.  2000,  41:  3271 
• 3b Connor JA. Gibson D. Price R. J. Chem. Soc., Perkin Trans. 1  1987,  619 
• 3c Tagaki K. Sakakibara Y. Chem. Lett.  1989,  1957 
• 3d Kubota H. Rice KC. Tetrahedron Lett.  1998,  39:  2907 
• 3e Adachi M. Sugasawa T. Synth. Commun.  1990,  20:  71 
• 3f Jackson WR. Perlmuter P. Chem. Ber.  1986,  338 
• 4 Yamaguchi K. Mizuno N. Angew. Chem. Int. Ed.  2003,  42:  1480 
• 5a Mlochowski J. Kloc K. Kubicz E. J. Prakt. Chem.  1994,  336:  467 
• 5b Carmeli M. Shefer N. Rozen S. Tetrahedron Lett.  2006,  47:  8969 
• 5c Stanković S. Espenson JH. Chem. Commun.  1998,  1579 
• 5d Ramalingam T. Reddy BVS. Srinivas R. Yadav JS. Synth. Commun.  2000,  30:  4507 
• 6a Ruck RT. Bergman RG. Angew. Chem. Int. Ed.  2004,  43:  5375 
• 6b Boruah M. Konwar D. J. Org. Chem.  2002,  67:  7138 ; and references cited therein
• 7 Yan M. Xu Q.-Y. Chan ASC. Tetrahedron: Asymmetry  2000,  11:  845 
• 8a Dewan SK. Singh R. Kumar A. ARKIVOC  2006,  (ii):  41 
• 8b Narsaiah AV. Sreenu D. Nagaiah K. Synth. Commun.  2006,  36:  137 
• 8c Heravi M. Khadijeh B. Shoar RH. Hossein OA. J. Chem. Res., Synop.  2005,  590 
• 8d Sarvari MH. Synthesis  2005,  787 
• 8e Niknam K. Karami B. Kiasar AR. Bull. Korean Chem. Soc.  2005,  26:  975 
• 8f Khan TA. Peruncheralathan S. Ila H. Junjappa H. Synlett  2004,  2019 
• 8g Sharghi H. Sarvari MH. Synthesis  2003,  243 
• 8h Yang SH. Chang S. Org. Lett.  2001,  3:  4209 
• 8i Lai G. Bhamare NK. Anderson WK. Synlett  2001,  230 
• 8j Tamami B. Kiasat AR. Synth. Commun.  2000,  30:  235 
• 8k Paraskar AS. Jagtap HS. Sudalai A. J. Chem. Res., Synop.  2000,  30 
• 8l Iranpoor N. Zeynizadeh B. Synth. Commun.  1999,  29:  2747 
• 8m Chaudhari SS. Akamanchi KG. Synth. Commun.  1999,  29:  1741 
• 8n Kumar HMS. Reddy BVS. Reddy PT. Yadav JS. Synthesis  1999,  586 
• 8o Kato Y. Ooi R. Asano Y. Mol. Cat. B. Enzym.  1999,  6:  249 
• 8p Ortiz-Marciales M. Pinero L. Algarin W. Morales J. Synth. Commun.  1998,  28:  2807 
• 8q Thomas HG. Greyn HD. Synthesis  1990,  129 
• 8r Saednya A. Synthesis  1983,  748 
• 9 Maeyama K. Kobayashi M. Kato H. Yonezawa N. Synth. Commun.  2002,  32:  2525 
• 10 Narashimhan NS. Mali RS. Barve MV. Synthesis  1979,  906 
• 11 Liebscher J. Hartman H. Z. Chem.  1975,  15:  302 
• 12 De Luca L. Giacomelli G. Riu A. J. Org. Chem.  2001,  66:  6823 
• 13 Quast H. Hergenroether T. Liebigs Ann. Chem.  1992,  581 
• 14 Vowinkel E. Bartel J. Chem. Ber.  1974,  107:  1221 
• 15 Loader CE. Anderson HJ. Can. J. Chem.  1981,  59:  2673 
• 16 Dictionary of Organic Compounds   4th ed., Vol. 5:  Pollock JRA. Stevens R. Oxford University Press; New York: 1965. 

17

Conversion of Aldoximes into Nitriles (Table 1); General Procedure: The appropriate aldoxime (3 mmol) in anhyd DMF (10 mL) was heated at 135 °C for 48 h. After cooling, the reaction mixture was diluted with H₂O (50 mL) and extracted with EtOAc (3 × 20 mL). The combined organic extracts were washed with brine (25 mL) and then dried (Na₂SO₄). The solvent was removed under vacuo and the crude product was purified by column chromatography (EtOAc-hexane, 1:4) to give the corresponding nitrile. The structure of the products was confirmed by comparison of their mp or bp, TLC, IR or ¹H NMR data with authentic samples obtained commercially or prepared by literature methods.
Preparation of 6-Bromo-2-hydroxynaphthalene-1-carbonitrile (Table 1, entry 13): Obtained as yellow microcrystals (EtOAc-hexane); yield: 0.48 g (68%); mp 202-203 °C. IR (Nujol): 3200, 2220 cm^-1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.32 (d, J = 9.2 Hz, 1 H, H-3), 7.77-781 (m, 2 H, H-7, H-8), 8.08 (d, J = 9.2 Hz, 1 H, H-4), 8.24 (s, 1 H, H-5), 11.85 (br s, 1 H, OH). MS (EI, 70 eV): m/z (%) = 246 (96) [M⁺], 221 (7), 192 (7), 140 (29), 113 (30), 87 (11), 70 (7), 63 (15), 50 (5). HRMS-EI: m/z [M⁺] calcd for C₁₁H₆BrNO: 246.9633; found: 246.9628.
Preparation of 4-Chloro-1-hydroxynaphthalene-2-carbonitrile (Table 1, entry 14): Obtained as yellow microcrystals (EtOAc-hexane); yield: 0.31 g (50%); mp 187-190 °C. IR (Nujol): 3200, 2200 cm^-1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.62-7.86 (m, 3 H, H-3, H-6, H-7), 8.11 (d, J = 7.0 Hz, 1 H, H-5), 8.40 (d, J = 8.4 Hz, 1 H, H-8), 8.62 (br s, 1 H, OH). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 93.78, 116.62, 121.38, 123.17, 123.71, 125.62, 126.23, 127.38, 130.66, 132.51, 158.07. MS (EI, 70 eV): m/z (%) = 203 (100) [M⁺], 174 (9), 148 (21), 140 (50), 113 (32), 88 (15), 74 (17), 63 (21), 50 (17). HRMS-EI: m/z [M⁺] calcd for C₁₁H₆ClNO: 203.0138; found: 203.0145.