Phase-Vanishing Method: Friedel-Crafts Acylation of Thiophene with Tin Tetrachloride and its Application to Convenient Parallel Synthesis

Abstract

Phase-vanishing (PV) method was applied to Friedel-Crafts acylations of aromatic compounds with tin tetrachloride as a Lewis acid. The reaction proceeded smoothly and acylation products were obtained in good yield. Parallel, four different Friedel-Crafts acylation reactions were carried out successfully based on the present PV method.

Key words

fluorous solvent - phase-vanishing - Friedel-Crafts acyl­ation - tin tetrachloride - parallel synthesis

References

• For leading reviews on fluorous chemistry, see:
• 1a Horváth IT. Acc. Chem. Res.  1998,  31:  641 
• 1b Curran DP. Angew. Chem. Int. Ed.  1998,  37:  1174 
• 1c Cornils B. Angew. Chem., Int. Ed. Engl.  1997,  36:  205 
• 1d Barthel-Rosa LP. Gladysz JA. Coord. Chem. Rev.  1999,  192:  587 
• 1e Luo Z. Zhang Q. Oderaotoshi Y. Curran DP. Science  2001,  291:  1766 
• 1f Curran DP. Synlett  2001,  1488 
• 1g A thematic issue of fluorous chemistry: Gladysz JA. Curran DP. Tetrahedron  2002,  58:  3823-4132  
• 2 Ryu I. Matsubara H. Yasuda S. Nakamura H. Curran DP. J. Am. Chem. Soc.  2002,  124:  12946 
• For recent work on fluorous triphasic reactions, see:
• 3a Luo Z. Swaleh SM. Theil F. Curran DP. Org. Lett.  2002,  4:  2585 
• 3b Nakamura H. Kinclau B. Curran DP. J. Am. Chem. Soc.  2002,  67:  1781 
• 4 For Friedel-Crafts acylation reactions of thiophene using tin tetrachloride and acetyl chloride, see: Johnson JR. May GE. Org. Synth., Coll. Vol. 2.   Blatt AH. Wiley; New York: 1943.  p.8 
• For recent examples of Friedel-Crafts reactions using tin tetrachloride, see:
• 5a Pivsa-Art S. Okuro K. Miura M. Murata S. Nomura M. J. Chem. Soc., Perkin Trans. 1  1994,  1703 
• 5b Casimir JR. Tourwé D. Iterbeke K. Guichard G. Briand J.-P. J. Org. Chem.  2000,  65:  6487 
• 5c Ottoni O. Neder A. de VF. Dias AKB. Cruz RPA. Aquino LB. Org. Lett.  2001,  3:  1005 
• 5d Inoue M. Carson MW. Frontier AJ. Danishefsky SJ. J. Am. Chem. Soc.  2001,  123:  1878 
• For reviews on Friedel-Crafts reactions, see:
• 6a Eyley SC. In Comprehensive Organic Synthesis   Vol. 2:  Pergamon Press; Oxford: 1991.  p.707 
• 6b Heany H. In Comprehensive Organic Synthesis   Vol. 2:  Pergamon Press; Oxford: 1991.  p.733 
• 6c Gore P. Chem. Rev.  1955,  55:  229 
• 6d Olah GA. Friedel-Crafts and Related Reactions   Vol. 1, 9:  Wiley; New York: 1963.  p.201 
• 6e Pearson DE. Buehler CA. Synthesis  1972,  533 
• 6f Gore P. Chem. Ind. (London)  1974,  727 
• 6g Olah GA. Meidar D. Kirk-Othmer Encyclopedia of Chemical Technology   Vol. 11, 3rd ed.:  Grayson M. Eckroth D. Wiley; New York: 1980.  p.269 

7

A typical experimental procedure: Tin tetrachloride (2.2 mmol, 573 mg) was added slowly to FC-72 (3 mL) in a test tube (14.4 mmφ × 130 mm) with a septum by using a glass pipette and then thiophene (2.0 mmol, 168 mg) and propionyl chloride (2.2 mmol, 204 mg) in benzene (3 mL) was added slowly, forming three layers. The bottom layer was stirred gently at 30 °C for 3 h, taking care not to mix the three layers. The dark purple benzene layer was taken up with a pipette. Additional benzene (2 mL × 4) was then placed on the residual FC-72 layer, followed by decanting off. The combined benzene layer was washed with 1 M HCl (20 mL × 2) and water (20 mL × 2), and dried over MgSO₄, and concentrated. Purification by a short column chromatography on silica gel with benzene gave 2-propionylthiophene (1.43 mmol, 201 mg) in 72% yield.

8

We confirmed that no contamination among products was observed in this parallel experiment under the conditions specified in Scheme [2] .