A Highly Active Ytterbium(III) Methide Complex for Truly Catalytic Friedel-Crafts Acylation Reactions

Abstract

The Friedel-Crafts acylation of anisole with acetic anhydride using ytterbium(III) tri[tris(nonafluorobutanesulfonyl)methide] was studied with respect to catalyst loading. A strong inhibitory effect due to the product became apparent from doping experiments and from examination of the kinetic data. This understanding allowed catalyst loadings to be reduced to as little as 0.1 mol% for effective acylation under a suitable temperature and pressure regime.

Key words

Friedel-Crafts - acylation - catalytic - ytterbium(III) methide - inhibition

References

• 1a Olah GA. Friedel-Crafts Chemistry   Wiley-Interscience; London: 1973. 
• 1b Heaney H. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.733 
• 2a Kawada A. Mitamura S. Kobayashi S. J. Chem. Soc., Chem. Commun.  1993,  1157 
• 2b Kawada A. Mitamura S. Kobayashi S. Synlett  1994,  545 
• 2c Hachiya I. Moriwaki M. Kobayshi S. Bull. Chem. Soc. Jpn.  1995,  68:  2053 
• 2d Kobayashi S. Iwamoto S. Tetrahedron Lett.  1998,  39:  4697 
• 3a Desmur JR. Labrouillere M. Le Roux C. Gaspard H. Laporterie A. Dubac J. Tetrahedron Lett.  1997,  38:  8871 
• 3b Repichet S. LeRoux C. Dubac J. Desmurs JR. Eur. J. Org. Chem.  1998,  2743 
• 4 Mikami K. Kotera O. Motoyama Y. Sakaguchi H. Maruta M. Synlett  1996,  171 
• 5 Fürstner A. Voightlander D. Schrader W. Giebel D. Reetz MT. Org. Lett.  2001,  3:  417 
• 6 Waller FJ. Barrett AGM. Braddock DC. Ramprasad D. McKinnell RM. White JP. Williams DJ. Ducray R. J. Org. Chem.  1999,  64:  2910 
• 7 Barrett AGM. Braddock DC. Ducray R. McKinnell RM. Waller FJ. Synlett  2000,  57 
• 8a Barrett AGM. Braddock DC. Catterick D. Chadwick D. Henschke JP. McKinnell RM. Synlett  2000,  847 
• 8b Barrett AGM. Bouloc N. Braddock DC. Catterick D. Chadwick D. White AJP. Williams DJ. Tetrahedron  2002,  58:  3835 
• 10a Mikami K. Mikami Y. Matsumoto Y. Nishikido J. Yamamoto F. Nakajimi H. Tetrahedron Lett.  2001,  42:  289 
• 10b Mikami K. Mikami Y. Matsuzawa H. Matsumoto Y. Nishikido J. Yamamoto F. Nakajima H. Tetrahedron  2002,  58:  4015 
• 11 For experimental details for the preparation of these complexes see: Barrett AGM. Bouloc N. Braddock DC. Catterick D. Chadwick D. White AJP. Williams DJ. Tetrahedron  2002,  58:  3835 

9

Catalytic Compounds and Processes. UK Patent Application No 9919583.6.

12

These plots were obtained using a Mettler-Toledo REACT-IR 4000 system with a dicomp probe scanning every 60 s
(25 °C, 50 °C) or 45 s (70 °C) for the first two hours followed by one scan every five min for the remaining time. The profiles are generated by following the peak area between 1672 and 1685 wave numbers to a constant baseline point.

13

General Experimental Procedure: A stirred solution of arene (0.6 mmol), anhydride (1.2 mL) and catalyst 1 (16 mg, 0.006 mmol) in PhCF₃ (1.2 mL) was heated to 150 °C in a sealed tube for 20 h. The resulting mixture was allowed to cool, diluted with Et₂O (10 mL), washed with water (2 × 10 mL), sat. aq sodium hydrogen carbonate solution (2 × 10 mL), sat. aq sodium chloride solution (2 × 10 mL), dried (MgSO₄), concentrated in vacuo and chromatographed.

14

IR and ^¹ H NMR for Friedel-Crafts Acylation Products: 4-Methoxyacetophenone: IR (KBr): 1676 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.58 (s, 3 H), 3.84 (s, 3 H), 6.96 (d, 2 H, J = 9.0 Hz), 7.95 (d, 2 H, J = 9.0 Hz). 4-Methoxy-isobutyrophenone: IR (KBr): 1675 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.20 (d, 6 H, J = 7.0 Hz), 3.53 (septet, 1 H, J = 7.0 Hz), 3.87 (s, 3 H), 6.94 (d, 2 H, J = 8.5 Hz), 7.95 (d, 2 H, J = 8.5 Hz). 4-Methoxybenzophenone: IR (KBr): 1650 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.91 (s, 3 H), 6.98 (d, 2 H, J = 8.0 Hz), 7.47-7.59 (m, 3 H), 7.78 (d, 2 H, 7.0 Hz), 7.85 (d, 2 H, J = 8.0 Hz). 4-Thiomethylace-tophenone: IR (KBr): 1673 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.55 (s, 3 H), 2.59 (s, 3 H), 7.28 (d, 2 H, J = 8.0 Hz), 7.89 (d, 2 H, J = 8.0 Hz). 4-Thiomethyl-isobutyro-phenone: IR (KBr): 1670 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.21 (d, 6 H, J = 7.0 Hz), 2.53 (s, 3 H), 3.51 (septet, 1 H, J = 7.0 Hz), 7.27 (d, 2 H, J = 8.5 Hz), 7.87 (d, 2 H, J = 8.5 Hz). 4-Thiomethylbenzophenone: IR (KBr): 1649 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.56 (s, 3 H), 7.28-7.32 (2 H, m), 7.48-7.65 (3 H, m), 7.72-7.80 (m, 4 H). 2-Acetylthiophene: IR (KBr): 1662 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 2.59 (s, 3 H), 7.15 (1 H, t, J = 4.0 Hz) 7.65 (d, 1 H, J = 4.0 Hz), 7.71 (d, 1 H, J = 4.0 Hz). 2-Isobutyryl-thiophene: IR (KBr): 1662 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.27 (d, 6 H, J = 7.0 Hz), 3.41 (septet, 1 H, J = 7.0 Hz) 7.15 (t, 1 H, J = 4.5 Hz) 7.65 (d, 1 H, J = 5.0 Hz), 7.75 (d, 1 H, J = 4.5 Hz). 2-Benzoylthiophene: IR (KBr): 1632 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.19 (t, 1 H, J = 3.5 Hz), 7.52-7.68 (m, 6 H), 7.87 (d, 2 H, J = 3.0 Hz). 5-Acetyl-3-methylthiophene: IR (KBr): 1662 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 2.29 (s, 3 H), 2.53 (s, 3 H), 7.22 (d, 1 H, J = 1.0 Hz), 7.49 (d, 1 H, J = 1.0 Hz). 2-Acetyl-3-methylthiophene: IR (KBr): 1662 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 2.29 (s, 3 H), 2.55 (s, 3 H), 6.93 (d, 1 H, J = 5.0 Hz), 7.39 (d, 1 H, J = 5.0 Hz). 2- and 5-Isobutyryl-3-methylthiophene: IR (KBr): 1660 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.23 (d, 6 H, J = 7.0 Hz), 2.13 (s, 1.05 H), 2.59 (s, 1.95 H), 3.32 (m, 1 H), 6.97 (d, 0.65 H, J = 5.0 Hz), 7.38 (s, 0.35 H), 7.40 (d, 0.65 H, J = 5.0 Hz), 7.55 (s, 0.35 H). 2- and 5-Benzoyl-3-methylthiophene: IR (KBr): 1633 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.34 (s, 1.2 H), 2.51 (s, 1.8 H), 7.03 (d, 0.6 H, J = 5.0 Hz), 7.34 (s, 0.4 H), 7.46-7.61 (m, 4 H), 7.86 (m, 2 H). 9-Benzoylanthracene: IR (KBr): 1656 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.39-7.61 (m, 7 H), 7.74 (d, 2 H, J = 8.5 Hz), 7.84 (d, 2 H, J = 7.0 Hz), 8.09 (d, 2 H, J = 8.5 Hz), 8.56 (s, 1 H). α- and β- Benz-oylnaphthalene: IR (KBr): 1659 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.46-7.65 (m, 7 H), 7.88-8.05 (m, 4 H), 8.11 (d, 0.65 H, J = 7.5 Hz), 8.29 (s, 0.35 H). 2,4-Dimethyl-benzophenone: IR (KBr): 1662 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.35 (s, 3 H), 2.41 (s, 3 H), 7.07 (d, 1 H, J = 7.0 Hz), 7.13 (s, 1 H), 7.25 (d, 1 H, J = 7.5 Hz), 7.47 (m, 2 H), 7.58 (m, 1 H), 7.81 (d, 2 H, J = 7.0 Hz). 2- and 4-Methyl-benzophenone: IR (KBr): 1658 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 0.4 H, 2-CH₃), 2.45 (s, 2.6 H, 4-CH₃), 7.29-7.82 (m, 9 H).