Arbuzov Reaction

Definition:

The reaction of alkyl halides with trialkyl phosphites to render monoalkylphosphonic esters.

Frequency of appearance:

        This bar graph represents all of the online articles that were found to contain this specific name reaction in the title of the article. Tetrahedron letters, Tetrahedron, Synthetic letters, Synthesis, Journal of Organic Chemistry and Journal of the American Chemical Society are represented here. This table by no means represents the periodicity of the name reaction found in the literature.

Original references:

1. Michaelis, R. Kaehne, Ber. 31, 1048 (1898).
2. A. E. Arbuzov, J. Russ. Phys. Chem. Soc. 38, 687 (1906).

Recent academic references: Click here for more references

3. Photo-Arbuzov Rearrangement of 1-Arylethyl Phosphites.

• Bhanthumnavin, W.; Bentrude, W. G.; J. Org. Chem., 66(3); 980-990 (2001).

4. Photo-Arbuzov Rearrangement of Benzylic Phosphites.

• Bhanthumnavin, W.; Arif, A.; Bentrude, W. G.; J. Org. Chem. 63(22); 7753-7758 (1998).  

5. Process Development for the Preparation of a Monopril Intermediate by a Trimthylsilyl-Modified Arbuzov Reaction

• Anderson, N. G.; et al.; Org. Process Res. Dev., 1(3); 211-216 (1997).

6. http://ohlab.kaist.ac.kr/paper/joc-nitrileoxide.pdf

Recent process references:

                                                    N/A

Mechanism:

                                                                    Unstable trialkoxyphosphonium intermediate

Scope and Limitations:

• Reactivity of halide I> Br > Cl ^B
• 2⁰ alkyl halides may exhibit HX elimination to form an alkene. ^B
• Arylhalides are unreactive.
• Reaction condition may require a temperature in excess of 80⁰C. ²
• Polar solvents may be effective in stabilizing the trialkoxyphosphonium intermediate. ²
• If the reaction conditions are not controlled the alkyhalide produced from the phosphonium salt may react with the original phosphite to give an undesired Arbuzov product.

Synonyms:

• Michaelis-Arbuzov