Organic Syntheses Procedure

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Org. Synth. 2012, 89, 82-87

DOI: 10.15227/orgsyn.089.0082

Discussion Addendum for: Efficient Synthesis of Halomethyl-2,2'-Bipyridines: 4,4'-Bis(Chloromethyl)-2,2'-Bipyridine

Submitted by Tiandong Liu and Cassandra L. Fraser*¹.

Original Article: Org. Synth. 2002, 78, 82

Discussion

Halogenation of dimethyl-2, 2'-bipyridines via trimethylsilyl (TMS) intermediates and electrophilic halide reagents, CX₃CX₃ (X = Cl, Br or F), is a very useful method for bipyridine (bpy) derivation.^2-⁴ This approach benefits from nearly quantitative yields, few by-products, and low cost reagents. In the past decade, there have been only a few improvements reported for this reaction, but many bipyridine derivatives have been prepared using this method. Many bipyridine analogues have been accessed via TMS-bpy intermediates.

Monohalogenation of Dimethyl-Bipyridine

Other common methods for methylpyridine halogenation involve radical reactions or hydroxymethylbipyridine precursors. The radical method suffers from high reactivity and poor selectivity, often generating mixtures of halogenated species, whereas hydroxyl halogenations typically involve multi-step processes.

Monohalogenation of dimethyl-bipyridine may be performed by the TMS procedure with a reduced amount of lithium diisopropylamide (LDA). The reported yields were nearly quantitative (~99%)⁶ for 5-bromomethyl-5'-methyl-2,2'-bipyridine and over 60% for 5-chloromethyl-5'-methyl-2,2'-bipyridine⁵ and. However, the same reaction with 4,4'-dimethyl-2,2'-bipyridine generated the monobromo product in only 35% yield.⁷

Figure 1. Monohalogenation of dimethyl-bipyridines.

Bipyridine Derivatization via Silane Reagents

Given that the trimethylsilyl-bpy reagents were good nucleophile precursors in the halogenation of dimethylbipyridine, their reactivity was extended to other electrophilic substrates, such as aldehydes² and alkylhalides.⁸ Tetrachlorosilane can also be used to trap lithium intermediates and generate reactive trichlorosilane species, which have been reacted with alcohols to generate trialkoxysilylmethyl bipyridines or hydroxyl groups on zeolite surfaces for catalysis.⁹ New derivatives are accessible via these approaches using various reagents and substrates.

Figure 2. Compounds derived from trimethylsilylmethyl bipyridine.

Polymers Containing Bipyridines

Bipyridyl units appear frequently in functionalized polymeric materials as ligands for metal atoms or to modify electronic or optical properties.^10-¹⁴ The bis(halomethyl)-bipyridine complexes and their corresponding compounds with ruthenium or iron were utilized as initiators to generate metallopolymers, including block polymers.^15-²¹

Figure 3. Bis(halomethyl) bipyridine in polymerization.

Bisphosphonate Bipyridine Complexes

Le Bozec, et al. used 4,4'-bis(bromomethyl)-2,2'-bipyridine to prepare 4,4'-bis(phosphonate)-2,2'-bipyridine, which can be used to produce many new derivatives via Wadsworth-Emmons reactions with aldehydes.²²^,²³ A similar approach was adopted by Grätzel and coworkers to generate bipyridines with extended π conjugation for solar cell applications.²⁴

Figure 4. Preparation of bis(phosphonate) bipyridine compounds.

References and Notes

Department of Chemistry, University of Virginia, Charlottesville, VA 22904, fraser@virginia.edu. We thank the National Science Foundation (CHE 0718879) for support for this work.
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Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

4,4'-BIS(CHLOROMETHYL)-2,2'-BIPYRIDINE (138219-98-4)

Cassandra L. Fraser was born in Norfolk, Virginia in 1962 and grew up in Michigan. She obtained a B.A. degree from Kalamazoo College in 1984, an M.T.S. degree from Harvard Divinity School in 1988, and a Ph.D. from The University of Chicago in 1993 with Brice Bosnich. After postdoctoral research with Robert Grubbs at Caltech from 1993-5, she joined the faculty in the Department of Chemistry at the University of Virginia, where she was promoted to Associate Professor in 2001 and Professor in 2005, now with joint appointments in Biomedical Engineering and Architecture. Her research involves luminescent materials for imaging and sensing in biomedicine and sustainable design.

Tiandong Liu was born in Nanjing, China in 1979. He obtained a B.S. degree from Nanjing University in 2001. He began his graduate work at the University of Virginia with Lin Pu exploring enantioselective luminescent sensors for chiral carboxylic acids in 2006 and in 2010 joined the Fraser group to explore boron complexes with optical oxygen sensing and mechanochromic luminescence properties.

Notes

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