Cleavage of tert-butyl benzoates with NaH in DMF: Comments on the mechanism and a simple and safe alternative procedure

Synlett

Volumn , Issue 2, 2009, Pages 205-208

  Filali, Emane ^a   Lloyd Jones, Guy C ^a   Sale, David A ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Cleavage; DMF; Hazard; Hydrides; tert butyl esters

Indexed keywords

EID: 62349107478     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0028-1087668     Document Type: Article

References (23)

1. See, for example: (a) Kocienski, P. J. Protecting Groups, 3rd ed.; Thieme: Stuttgart, 2003.
2. (b) Wuts, P. G. M.; Greene, T. W. Greene's Protective Groups in Organic Synthesis, 4th ed.; John Wiley and Sons: New Jersey, 2007.
3. Paul, S.; Schmidt, R. R. Synlett 2002, 1107.
4. 2 and CO, or formaldehyde: (a) Nasipuri, D.; Bhattacharya, A.; Hazra, B. G. J. Chem. Soc. D 1971, 660.
5. (b) Powers, J. C.; Seidner, R.; Parsons, T. G. Tetrahedron Lett. 1965, 6, 1713.
6. Mixtures of NaH and DMF can undergo uncontrollable exothermic decomposition at temperatures as low as 26°C, with higher onset temperatures in very dry solvent. In some cases these exothermic reactions have resulted in violent eruptions of the mixture from the reaction vessel, in particular when conducted at scale. See: Bretherick, L. Handbook of Reactive Chemical Hazards, 4th ed.; Butterworth-Heinemann: Oxford, 1990, 1181; and references therein.
7. For the synthesis of unlabelled parent compound 2a, see: Hoots, J. E.; Rauchfuss, T. B.; Wrobleski, D. A. Inorg. Synth. 1982, 21, 175.
8. Serrano-Wu, M. H.; Regueiro-Ren, A.; St. Laurent, D. R.; Carroll, T. M.; Balabsubramanian, B. N. Tetrahedron Lett. 2001, 42, 8593.
9. 2 and NaH in anhydrous THF proceeded to 45% conversion (to 4b) over a period of 4 d.
10. Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic Chemistry, 3rd ed.; Harper and Row: New York, 1987, 718-719.
11. Gassman, P. G.; Schenk, W. N. J. Org. Chem. 1977, 42, 918.
12. Roberts, W.; Whiting, M. C. J. Chem. Soc. 1965, 1290.
13. Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017.
14. NaOH in DMF was less effective, see ref. 7. For reactions in THF, replacement of KOH by NaOH or LiOH led to a significant reduction in yield of 2a from 1a. Reduction in the formal number of equivalents of KOH results in a reduction of reaction rate. Increasing to 16 equiv of KOH resulted in quantitative conversion of 3a to 4a in <2 h.These effects may relate to the surface area of the KOH exposed to the THF medium.
15. 18
16. 18
17. For the reduction of ArI to ArH by NaH in THF, see: (a) Nelson, R. B.; Gribble, G. W. J. Org. Chem. 1974, 39, 1425.
18. (b) For the reduction of methyl o-iodobenzoate by NaOMe, MeOH, with radiation (λ = 350 nm), to methyl benzoate, see: Kashimura, T.; Kudo, K.; Mori, S.; Sugita, N. Chem. Lett. 1986, 851.
19. 4) and anecdotal evidence of such occurrences. These strongly support the conclusion that the procedure in Scheme 2 is potentially very hazardous.
20. (a) Furniss, B. S.; Handford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel's Textbook of Practical Organic Chemistry, 5th ed.; Longman: London, 1989.
21. (b) Krasnokutskaya, E. A.; Semenischeva, N. I.; Filimonov, V. D.; Knochel, P. Synthesis 2007, 81.
22. Spectroscopic data were identical to those obtained from commercially available samples (Aldrich) of 4a and 4c.
23. Concise Chemical and Technical Dictionary, 1st ed.; Bennett, H., Ed.; Chemical Publishing Co.: New York, 1947, 107.