Introduction to the preparation and use of 5-bromo-2-iodopyridine_Industrial additives

Background and overview of the preparation and use of 5-bromo-2-iodopyridine

5-Bromo-2-iodopyridine is an organic intermediate that can be obtained by halogen replacement of 2,5-dibromopyridine with sodium iodide. There are reports in the literature that it can be used to prepare the electrochromic compound 1,1″′-dihexyl-[4,3′:6′,2″:5″,4″′-tetrapyridine]-1,1″′- Dionium bis(tetrafluoroborate) (II-3a) and 1,1″′-dihexyl-1′,1″-dimethyl-[4,3′:6′,2″:5″, 4″′-tetrabipyridyl]-1,1′,1″,1″′-tetrakis(tetrafluoroborate).

Introduction to the preparation and use of 5-bromo-2-iodopyridine

Potassium trifluoroborate aqueous HI (57%) was added to 2,5-dibromopyridine (12.60g, 53.2mmol) and NaI (11.40g, 76mmol). The resulting mixture was heated at reflux for 24 h, cooled and then diluted with water (100 mL). The resulting mixture was basified with NaHCO3 and treated with Na2S2O4 until colorless. The mixture was extracted with DCM (5 x 60 mL) and the dry (Na2SO4) solvent was removed under reduced pressure. The residue was collected by filtration and washed with Et2O (60 mL) and air dried to give 5-bromo-2-iodopyridine (8.28 g, 55%) as a light gray powder.

Preparation and application of 5-bromo-2-iodopyridine

5-Bromo-2-iodopyridine can be used to prepare 1,1″&prchloropyridine im;-dihexyl-[4,3′:6′,2″:5″,4″′-tetrapyridine] -1,1″′-diium bis(tetrafluoroborate) (II-3a) and 1,1″′-dihexyl-1′,1″-dimethyl-[4,3′:6′ ,2″:5″,4″′-tetrabipyridyl]-1,1′,1″,1″′-tetrakis(tetrafluoroborate), this compound is an electrochromic compound. Here’s how:

5-Bromo-2-iodopyridine (6.60g, 23.2mmol) and Pd(PPh3)4 (0.72g, 0.6mmol) were dissolved in anhydrous PhMe (120mL) under N2. Hexa-n-butyldistin (7.25 g, 12.5 mmol) was added and the solution was heated at reflux for 3 days. The mixture was filtered through Celite and the solvent was removed. The residue was chromatographed on silica using a DCM to EtOAc gradient. The resulting residue was crystallized from EtOAc/hexane to give 5,5′-dibromo-2,2′-bipyridine (1.22 g, 33%) as a pale yellow powder. The crystallization liquid was evaporated under reduced pressure and the residue was dissolved in DCM, hexane was added and the volume of solvent was reduced. The resulting precipitate was collected by filtration and air dried to give a second batch of product as a cream colored powder (0.46 g, 13%).

Place 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.38g, 11.6mmol), 5,5′ -Dibromo-2,2′-bipyridyl (1.46 g, 4.6 mmol), K2CO3 (1.6 g, 11.6 mmol) and Pd(PPh3)4 (0.27 g, 5 mol%) in degassed EtOH (40 mL) and PhMe (40 mL) was heated at reflux under N2 for 48 h. The mixture was cooled, diluted with water (200 mL) and poured into DCM (1.5 L) containing MeOH (150 mL) and filtered through celite. The aforementioned celite was extracted with DCM (800 mL) and MeOH (100 mL) and the combined DCM and MeOH extracts were filtered through celite. Repeat the extraction/filtration sequence 3 more times. The organic phases were combined and filtered again through Celite, at which time the solvent was removed under reduced pressure and the residue was triturated with hot acetone (100 mL). The ground solid was collected by filtration and air dried to give 4,3′:6′,2″:5″,4″‘-tetrapyridine (1.18 g, 82%) as a light tan powder. The liquid was cooled and the precipitated solid was collected by filtration to give a second batch of product as a pale pink powder (0.15g, 10%).

Dissolve 4,3′:6′,2″:5″,4″′-tetrapyridine (0.60g, 1.9mmol) and 1-iodohexane (2.46g, 11.6mmol) in MeCN (50mL) The solution in was heated at reflux under N2 in the dark for 24 h. Once cooled, the solid was collected by filtration and washed with Et2O (3 × 50 mL) and air dried to give 1,1″′-bis as a sandy powder. Hexyl-[4,3′:6′,2″:5″,4″′-tetrapyridine]-1,1″′-diiodide (1.05 g, 74%). The liquid was diluted with Et2O (30 mL) and the precipitated solid was collected by filtration and washed with Et2O (2 x 30 mL) and air dried to give a second batch of product (0.11 g, 8%).

While stirring, 1,1″′-dihexyl-[4,3′:6′,2″:5″,4″′-tetrapyridine]-1,1″′-diium diiodo A filtered solution of NaBF4 (1.00 g, 1.36 mmol) in hot MeOH (100 mL) was added dropwise to a solution of NaBF4 (12 g, 109 mmol) in water (200 mL). Stirring was continued for 0.5 h, and the resulting precipitate was passed through Collect by filtration and wash with water (2 x 10 mL). The aforementioned solid was dissolved in hot MeOH (150 mL) and added dropwise to a solution of NaBF4 (12 g, 109 mmol) in water (250 mL) with stirring. Stirring was continued for 0.5 h, and the resulting precipitate was then collected by filtration, washed with water (2×10 mL) and air dried to give 1,1″′-dihexyl-[4,3′:6 as a tan powder ′,2″:5″,4″′-tetrabipyridyl]-1,1″′-diium bis(tetrafluoroborate) (II-3a) (0.76g, 85%), which was used directly in subsequent steps.

Place 1,1″′-dihexyl-[4,3′:6′,2″:5″,4″′-tetrapyridine]-1,1″ A mixture of ‘-dionium bis(tetrafluoroborate) (0.56g, 0.86mmol) in methyl tosylate (3.18g) was heated at 180°C for 2.5h. The cooled reaction mixture was triturated with Et2O (40 mL) and the solid was collected by filtration and washed with Et2O (3 x 40 mL) and air dried. The aforementioned solid was dissolved in methyl tosylate (1.71 g) and heated at 180°C for 1 h. The cooled mixture was triturated with Et2O (4 x 30 mL), collected by filtration and air dried. The resulting colloidal solid was dissolved in MeOH/water (25 mL, 1/4) and added dropwise to a solution of NaBF4 (3.38 g, 30.7 mmol) in water (50 mL) with stirring. Stirring was continued for 0.5 h, and the resulting precipitate was collected by filtration, washed with water (2×5 mL) and air dried. This solid was triturated with hot MeOH (8 mL) and the resulting solid was collected by filtration and washed with cold MeOH (2 mL) to give 1,1″‘-dihexyl-1’,1″- as a cream colored powder. Dimethyl-[4,3′:6′,2″:5″,4″′-tetrabipyridine]-1,1′,1″,1″′-tetrakis(tetrafluoroborate) (0.38g, 51%).

References

[1] From Eur. Pat. Appl., 3345981, 11 Jul 2018