Entirely Solvent-Free Procedure for the Synthesis of Distillable 1,3-Dithianes Using Lithium Tetrafluoroborate as a Reusable Catalyst

Abstract

Treatment of various types of aldehydes and ketones with 1,3-propanedithiol in the presence of a catalytic amount of lithium tetrafluoroborate at 25 °C under solvent-free conditions followed by direct purification by distillation of the resulting mixture affords the corresponding 1,3-dithianes in good to excellent yields. Chemoselective protection of keto aldehydes is also successfully achieved over the catalyst. The catalyst can be recovered and reused.

Key words

chemoselectivity - 1,3-dithiane - Lewis acids - lithium tetrafluoroborate - protecting groups

References

• For reviews, see:
• 1a Loewenthal HJE. In Protective Groups in Organic Chemistry   McOmie JFW. Plenum; London: 1973.  p.334-337  
• 1b Kocienski PJ. In Protecting Groups   Thieme; New York: 1994.  p.171-178  
• 1c Greene TW. Wuts PGM. In Protective Groups in Organic Synthesis   3rd ed.:  Wiley; New York: 1999.  p.333-344  
• For reviews, see:
• 2a Krief A. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon; Oxford: 1991.  p.85-191  
• 2b Yus M. Nájera C. Foubelo F. Tetrahedron  2003,  59:  6147 
• 3 For a review, see: Pettit GR. van Tamelen EE. Org. React.  1962,  12:  356 
• 4 For other synthetic applications, see: Luh T.-Y. J. Organomet. Chem.  2002,  653:  209 ; and references cited therein
• 5 For a recent leading reference, see: Kobayashi S. Iimura S. Manabe K. Chem. Lett.  2002,  10 
• For recent leading references, see:
• 6a Rana KK. Guin C. Jana S. Roy SC. Tetrahedron Lett.  2003,  44:  8597 ; and references cited therein
• 6b Kamel A. Chouhan G. Tetrahedron Lett.  2003,  44:  3337 
• 6c Khan AT. Mondal E. Sahu PR. Islam S. Tetrahedron Lett.  2003,  44:  919 
• 6d For dithioacetalization using LiOTf/neat: Firouzabadi H. Eslami S. Karimi B. Bull. Chem. Soc. Jpn.  2001,  74:  2401 
• 6e Firouzabadi H. Karimi B. Eslami S. Tetrahedron Lett.  1999,  40:  4055 
• 6f For dithioacetalization using LiBF₄/CH₃CN: Yadav JS. Reddy BVS. Pandey SK. Synlett  2001,  238 
• 6g For dithioacetalization using LiClO₄/diethyl ether: Saraswathy VG. Sankararaman S. J. Org. Chem.  1994,  59:  4665 
• 6h Tietze LF. Weigand B. Wulff C. Synthesis  2000,  69 
• 6i For dithioacetalization using LiBr/neat: Firouzabadi H. Iranpoor N. Karimi B. Synthesis  1999,  58 
• For recent leading references, see:
• 7a Hon Y.-S. Lee C.-F. Chen R.-J. Huang Y.-F. Synth. Commun.  2003,  33:  2829 ; and references cited therein
• 7b Firouzabadi H. Iranpoor N. Amani K. Synthesis  2002,  59 
• 8 For a recent review, see: Tanaka K. Solvent-free Organic Synthesis   Wiley-VCH; Weinheim: 2003. 
• 9 Anastas PT. Warner JC. In Green Chemistry: Theory and Practice   Oxford; London: 1998.  p.115-119  
• For recent leading references, see:
• 10a Yadav JS. Reddy BVS. Vishmumurthy P. Tetrahedron Lett.  2003,  44:  5691 ; and references cited therein
• 10b Kazemi F. Kiasat AR. Ebrahim S. Synth. Commun.  2003,  33:  999 
• 10c Kazemi F. Kiasat AR. Ebrahim S. Synth. Commun.  2003,  33:  595 
• 12 For a review, see: Gandini A. Adv. Polym. Sci.  1977,  25:  47 
• 14 For example, see: Corey EJ. Shimoji K. Tetrahedron Lett.  1983,  24:  169 
• As far as we know, the present system is the first example for the synthesis of 1,3-dithianes under entirely solvent-free conditions, although our procedure is applicable for only distillable such compounds. Though 1,3-dithiane synthesis under solvent-free conditions has been reported in some cases, unfortunately, all of these used organic solvents in the work-up processes:
• 16a

  ref. 6d,e.

• 16b

  ref. 6i.

• 16c

  ref. 7b.

• 16d Laskar DD. Prajapati D. Sandhu JS. J. Chem. Res., Synop.  2001,  313 
• 16e Firouzabadi H. Iranpoor N. Kohmareh G. Synth. Commun.  2003,  33:  167 

11

LiBF₄ was the best catalyst among the lithium salts tested under identical conditions: LiOTf (41%), LiCl (4%), LiClO₄ (36%), LiBr (16%), LiI (39%).

13

It is important to note that ketones were efficiently thioacetalized in our method, whereas LiBF₄/MeCN has been an ineffective reaction system, and the substrates remained intact after prolonged reaction times. [6f]

15

Only a few methods are known in the literature for the chemoselective protection of aldehydes in the presence of ketones: ref. 6c and references cited therein.

17

1,2-Ethanedithiol worked equally well under the same reaction conditions. For example, treatment of benzaldehyde (6.5 mmol) with 1,2-ethanedithiol (5 mmol) in the presence of LiBF₄ (0.5 mmol) at 25 °C for 1 h afforded 2-phenyl-1,3-dithiolane in 99% yield.