An Easy Access to Aromatic Azo Compounds under Ultrasound/Microwave Irradiation

Giancarlo Cravotto; Luisa Boffa; Marco Bia; Werner Bonrath; Massimo Curini; Georgios A. Heropoulos

doi:10.1055/s-2006-951481

LETTER

An Easy Access to Aromatic Azo Compounds under Ultrasound/Microwave Irradiation

Giancarlo Cravotto*^a, Luisa Boffa^a, Marco Bia^a, Werner Bonrath^b, Massimo Curini^c, Georgios A. Heropoulos^d
^a Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Giuria 9, 10125 Torino, Italy
Fax: +39(011)6707687 ; e-Mail: giancarlo.cravotto@unito.it;
^b DSM Nutritional Products, Research and Development, P.O. Box 32, 002 Basel, Switzerland
^c Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 06123 Perugia, Italy
^d Institute of Organic and Pharmaceutical Chemistry, National Hellenic Res. Found., Vas. Constantinou Av. 48, Athens 116 35, Greece

Abstract

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Abstract

Chemoselective reduction of nitroarenes to azo and azoxy compounds was easily achieved using zinc powder and ammonium chloride in DMF or DMF-water (95:5) under high intensity ultrasound (US) or microwave (MW) irradiation, separately or combined. When carried out under conventional heating the reaction required much higher temperatures and gave lower yields. The addition of a small amount of water caused a dramatic increase in the reactivity, permitting the reduction of hindered nitroarenes at the expense of selectivity. A novel reactor for combined US/MW irradiation was employed which demonstrated additional beneficial effects.

Key words

nitroarenes - azo compounds - reduction - ultrasound - microwave

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References

References and Notes

<A NAME="RG24206ST-1">1</A> Carrara G. Ann. Chim. Appl. 1933, 23: 140 ; Chem. Abstr. 1933, 27, 48401

<A NAME="RG24206ST-2">2</A> Wilman DE. Biochem. Soc. Trans. 1986, 14: 375

<A NAME="RG24206ST-3">3</A> Carceller E. Salas J. Merlos M. Giral M. Ferrando R. Escamilla I. Ramis J. Garcia-Rafanell J. Forn J. J. Med. Chem. 2001, 44: 3001

<A NAME="RG24206ST-4">4</A> Cravotto G. Beggiato M. Palmisano G. Penoni A. Lévêque JM. Bonrath W. Tetrahedron Lett. 2005, 46: 2267

<A NAME="RG24206ST-5A">5a</A> The Chemistry of Diazonium and Diazo Groups Patai S. Wiley; New York: 1978.

<A NAME="RG24206ST-5B">5b</A> Burke SD. Grieco PA. Org. React. (N.Y.) 1979, 26: 361

<A NAME="RG24206ST-5C">5c</A> Wulfman DS. Poling B. In Reactive Intermediates Vol. 1: Abramovitch RA. Plenum Press; New York: 1980. p.321

<A NAME="RG24206ST-5D">5d</A> Doyle MP. In Catalysis of Organic Reactions Augustine RL. Marcel Dekker; New York: 1985. Chap. 4.

<A NAME="RG24206ST-5E">5e</A> Doyle MP. Chem. Rev. 1986, 86: 919

<A NAME="RG24206ST-5F">5f</A> Doyle MP. Acc. Chem. Res. 1986, 19: 348

<A NAME="RG24206ST-5G">5g</A> Maas G. Top. Curr. Chem. 1987, 137: 75

<A NAME="RG24206ST-5H">5h</A> Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds John Wiley & Sons; Chichester: 1998.

<A NAME="RG24206ST-6">6</A> Gowda S. Gowda DC. Synthesis 2002, 460

<A NAME="RG24206ST-7">7</A> Srinivasa GR. Abiraj K. Gowda DC. Synth. Commun. 2003, 33: 4221

<A NAME="RG24206ST-8">8</A> Srinivasa GR. Abiraj K. Gowda DC. Tetrahedron Lett. 2003, 44: 5835

<A NAME="RG24206ST-9">9</A> Laskar DD. Prajapati D. Sandhu JS. J. Chem. Soc., Perkin Trans. 1 2000, 67

<A NAME="RG24206ST-10">10</A> Pyo SH. Han BH. Bull. Korean Chem. Soc. 1995, 16: 181

<A NAME="RG24206ST-11">11</A> Ung S. Falguières A. Guy A. Ferroud C. Tetrahedron Lett. 2005, 46: 5913

<A NAME="RG24206ST-12">12</A> Pasha MA. Jayashankara VP. Ultrason. Sonochem. 2006, 13: 42

<A NAME="RG24206ST-13">13</A> Cravotto G. Cintas P. Chem. Soc. Rev. 2006, 35: 180

<A NAME="RG24206ST-14">14</A> Kappe CO. Angew. Chem. Int. Ed. 2004, 43: 6250

<A NAME="RG24206ST-15">15</A> Lévêque JM. Cravotto G. Chimia 2006, 60: 313

<A NAME="RG24206ST-16">16</A> Cravotto G, Omiccioli G, Buffa C, and Dal Lago G. inventors; Patent VR 2004A000167 IT.

The disappearance of asymmetric and symmetric stretching bands due to the N-O of NO₂ (near 1520 cm^-1 and 1345 cm^-1 and the appearance of a strong band around 1460 cm^-1 due to N=N stretching was diagnostic. All the azo and azoxy compounds were fully characterised by IR, mass and NMR spectroscopy and when available compared with published data.

General Procedure: To a suspension of the nitro compound (1 mmol) and Zn powder (4 mmol) in DMF (5 mL) or DMF-H₂O (95:5, 5 mL, substrates 4, 5, 7, 8) NH₄Cl (2 mmol) was added under stirring and the mixture was heated or irradiated by US or/and MW as indicated before. After the reaction (monitored by TLC or GC) was complete, the mixture was filtered through a pad of celite and washed with H₂O and EtOAc. The organic layer was washed with brine, dried with anhyd Na₂SO₄, concentrated under vacuum and purified either by preparative TLC or by flash chromatography. (For substrate 1, reaction at 80 °C: the product was precipitated with 2 N HCl and the mixture was stirred until the Zn powder had completely dissolved. The crude product was collected on a Hirsch funnel and dried under vacuum.)

GC analyses were carried out on a Shimadzu-14B gas chromatograph, using SE52 capillary column (length 25 m; internal diameter 0.25 mm; film thickness 0.25 µm). GC conditions: injection split, 1:20; injector temperature, 250 °C; detector temperature, 300 °C; temperature program: from 50 °C (1 min) to 300 °C at 10 °C/min (30 min); H₂ as carrier gas at 25 kPa. The analysed products had the following retention time: 6: t _R 16.2 min; azo-6: t _R 27.3 min; azoxy-6: t _R 29.4 min; 7: t _R 14.9 min; azoxy-7: t _R 25.3 min; 8: t _R 14.4 min; azoxy-8: t _R 24.2 min.

1,2-Bis{4-[2-(2,2-dichloroacetamido)-1,3-dihydroxy-propyl]phenyl}diazene Oxide: Orange powder; mp 248.7 °C (dec.); R _f 0.52 (CHCl₃-MeOH, 8:2). IR (KBr): 3400 (OH, NH), 2926, 1674 (C=O), 1541 (NCO), 1464 (N=NO), 1196, 1074, 810, 774 cm^-1. ¹H NMR (300 MHz, acetone-d ₆): δ = 8.24 (d, J = 8.7 Hz, 2 H, ArH-2,6), 8.15 (d, J = 8.7 Hz, 2 H, ArH-2′,6′), 7.65 (d, J = 8.7 Hz, 2 H, ArH-3,5), 7.59 (d, J = 8.7 Hz, 2 H, ArH-3′,5′), 7.35 (br m, 2 H, CONH), 6.42 (s, 1 H, COCHCl₂), 6.41 (s, 1 H, COCH′Cl₂), 5.28 (d, J = 2.4 Hz, 1 H, PhCHOH), 5.23 (d, J = 2.4 Hz, 1 H, PhCH′OH), 5.19 (br, 1 H, PhCHOH), 5.08 (br, 1 H, PhCHOH′), 4.23 (br, 2 H, CH₂OH), 4.17 (m, 2 H, NHCH), 3.83 (m, 2 H, CH ₂OH), 3.74 (m, 2 H, CH′₂OH). ¹³C NMR (75 MHz, acetone-d ₆): δ = 164.27, 164.25 (CONH), 147.6 (ArC-1), 147.5 (ArC-1′), 145.1 (ArC-4′), 143.4 (C-4), 127.2 (ArC-3,5), 126.9 (ArC-3′,5′), 125.5 (ArC-2′,6′), 122.1 (ArC-2,6), 70.6 (PhCHOH), 70.3 (PhC′HOH), 67.1 (COCHCl₂), 67.0 (COC′HCl₂), 61.3 (CH₂OH), 57.7 (NHCH), 57.6 (NHC′H). MS (ESI): m/z = 621 [M⁺ + Na].

1,2-Bis[3,4-di(pentan-3-yl)phenyl]diazene: Orange powder; mp 97.2 °C; R _f 0.71 (hexane-EtOAc, 99:1). IR (KBr): 2963, 2872, 1458 (N=N), 1375, 901, 839, 812 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.76 (s, 2 H, H-2,2′), 7.65 (d, 2 H, H-6,6′), 7.34 (d, 2 H, H-5,5′), 2.91 [m, 4 H, CH(CH₂CH₃)₂], 1.92-1.55 [m, 16 H, CH(CH ₂CH₃)₂], 0.88-0.79 [m, 24 H, CH(CH₂CH ₃)₂]. ¹³C NMR (75 MHz, CDCl₃): δ = 151.1 (C-1,1′), 147.8 (C-4,4′), 145.6 (C-3,3′), 127.1 (C-5,5′), 122.9 (C-2,2′), 118.2 (C-6,6′), 42.2 [CH(CH₂CH₃)₂], 29.5, 29.2, 29.1 [CH(CH₂CH₃)₂], 12.5, 12.4, 12.3 [CH(CH₂ CH₃)₂]. MS (CI, isobutane): m/z (%) = 463 (100) [MH]⁺.

1,2-Bis[3,4-di(pentan-3-yl)phenyl]diazene Oxide: Yellow powder; mp 114.2 °C; R _f 0.64 (hexane-EtOAc, 99:1). IR (KBr): 2961, 2872, 1483, 1460 (N=NO), 1397, 928, 826 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.20-8.06 (overlap, 3 H, H-2,6,6′), 7.99 (s, 1 H, H-2′), 7.31 (d, 2 H, H-5,5′), 2.94 [br m, 4 H, CH(CH₂CH₃)₂], 1.91-1.52 [m, 16 H, CH(CH ₂CH₃)₂], 0.92-0.78 [m, 24 H, CH(CH₂CH ₃)₂]. ¹³C NMR (75 MHz, CDCl₃): δ = 148.5 (C-1), 146.8 (C-1′), 145.7 (C-3), 145.1 (C-3′), 142.4 (C-4,4′), 126.7 (C-2′), 126.4 (C-5′), 124.2 (C-5), 122.8 (C-2), 120.1 (C-6′), 119.7 (C-6), 42.6 [CH(CH₂CH₃)₂], 29.5, 29.4, 29.3 [CH(CH₂CH₃)₂], 12.6, 12.5, 12.4 [CH(CH₂ CH₃)₂]. MS (CI, isobutane): m/z (%) = 479 (53) [MH]⁺, 463 (100) [MH - O]⁺.

1,2-Bis[2,4-di(pentan-3-yl)phenyl]diazene: Orange oil; R _f 0.57 (hexane-EtOAc, 95:5). IR (film): 2963, 2874, 1603, 1456 (N=NO), 1379, 1173, 907, 831, 818 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.10-8.07 (d, 1 H, H-6), 7.42-7.40 (d, 1 H, H-6′), 7.07-7.05 (overlap, 4 H, H-3,5,3′,5′), 3.10-3.05 [m, 1 H, 2-CH(CH₂CH₃)₂], 2.95-2.90 [m, 1 H, 2′-CH(CH₂CH₃)₂], 2.50-2.25 [m, 2 H, 4,4′-CH(CH₂CH₃)₂], 1.81-1.49 [m, 16 H, CH(CH ₂CH₃)₂], 0.91-0.73 [m, 24 H, CH(CH₂CH ₃)₂]. ¹³C NMR (75 MHz, CDCl₃): δ = 147.6 (C-1), 146.6 (C-1′), 141.9 (C-2), 141.2 (C-4,4′), 138.4 (C-2′), 126.9 (C-3′), 126.8 (C-3), 125.5 (C-5′), 124.8 (C-5), 123.2 (C-6′), 121.1 (C-6), 49.8, 49.7 [4,4′-CH(CH₂CH₃)₂], 42.3, 42.2 [2,2′-CH(CH₂CH₃)₂], 29.3, 29.2, 29.0 [CH(CH₂CH₃)₂], 12.4, 12.3, 12.2 [CH(CH₂ CH₃)₂]. MS (CI, isobutane): m/z (%) = 479 (65) [MH]⁺, 463 (100) [MH - O]⁺.

1,2-Bis[2,5-di(pentan-3-yl)phenyl]diazene Oxide: Orange oil; R _f 0.59 (hexane-EtOAc, 99:1). IR (film): 2963, 2930, 2874, 1462, 1456 (N=NO), 1379, 1073, 882, 830 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.83 (s, 1 H, H-6), 7.31-7.20 (overlap, 4 H, H-3,3′,4′,6′), 7.13 (d, 1 H, H-4), 2.95 [br m, 2 H, 2,2′-CH(CH₂CH₃)₂], 2.42 [br m, 2 H, 5,5′-CH(CH₂CH₃)₂], 1.84-1.59 [m, 16 H, CH(CH ₂CH₃)₂], 0.90-0.75 [m, 24 H, CH(CH₂CH ₃)₂]. ¹³C NMR (75 MHz, CDCl₃): δ = 144.3 (C-1), 143.4 (C-1′), 143.1 (C-2), 139.2 (C-5,5′), 136.1 (C-2′), 129.3 (C-4′), 127.9 (C-3′), 127.1 (C-3), 126.8 (C-4), 122.6 (C-6′), 120.5 (C-6), 49.3, 49.1 [2,2′-CH(CH₂CH₃)₂], 42.5, 42.0 [5,5′-CH(CH₂CH₃)₂], 29.2, 29.1, 28.8 [CH(CH₂CH₃)₂], 12.4, 12.3, 12.2 [CH(CH₂ CH₃)₂]. MS (CI, isobutane): m/z (%) = 479 (100) [MH]⁺, 463 (27) [MH - O]⁺.