Pyridinium fluorides

The 2-(trimethylsilyl)ethoxymethyl group (SEM) can be removed by various fluoride sources, including TBAF, pyridinium fluoride, and HF.165 This deprotection involves nucleophilic attack at silicon, which triggers (3-elimination. 

Fluorodediazoniation in anhydrous hydrogen fluoride has been also applied to the synthesis of fluorinated heterocycles, especially pyridines 2. In this case, the reaction is more sensitive to the reaction conditions. For example, diazotization must be performed at lower temperatures than usual and the dediazoniation temperature must be raised slowly in order to obtain good yields. Workup is also important addition of dichloromethane prior to neutralization with ammonia32 as well as treatment of the organic phase with calcium hydride before distillation33 has been recommended, particularly for 4-fluoropyridines (4-fluoropyridine itself forms 4-fluoro-l-(4-pyridyl)pyridinium fluoride if not stored in a sealed tube with cooling33 or stabilized as the hydrochloride32). 

Ethoxy Methoxy Tellurium Tetrafluorlde1 1.0 g (3.7 mmol) of ethoxy tellurium pentafluoride are dissolved in 10 m/ of carbon tetrachloride, 0.4 g (12.5 mmol) of methanol are added, and the mixture is cooled to — 20u. 0.4 g (5.1 mmol) of pyridine are added dropwise to the cold solution, the mixture is extracted with very dilute hydrochloric acid to remove pyridinium fluoride, and the organic layer is separated, and dried with anhydrous sodium sulfate. The mixture is filtered, carbon tetrachloride is distilled off under reduced pressure, and the product is distilled under vacuum yield 0.65 g (63%) b.p. 65°/20 torr. 

Table II. Synthesis and Pyrolysis of N-Subsliluled Pyridinium Fluorides and Tetrafluoroborates " ...

Alkyl and benzyl fluorides Pyridinium fluorides (2) result from reaction of primary amines and 1 with removal of water by azeotropic distillation with benzene-ethanol. These pyridinium fluorides decompose smoothly at 80-120° to afford the corresponding alkyl and benzyl fluorides (3). 

As pointed out briefly in Chapter 6 (Table 6.1), the ionic addition of hydrogen fluoride (HF) across the carbon-carbon double bond of alkenes produces alkyl fluorides. Generally, the addition is effected by treating a solution of alkene in an ethereal solvent (e.g., tetrahydrofuran [THF]) with a pyridine solution of HF, which must thus contain pyridinium fluoride (Equation 7.1). 

The synthesis of a series of 2 -fluoro-5-substituted arabinofuran-osyl-cytosines and -uracils has been described. 5-Methyluracil and 5-iodocytosine derivatives were the most effective against herpes simplex virus. The arabino configuration was essential for antibiotic activity, and corresponding chloro and bromo analogues were less effective.5 -Bromo-, 5 -fluoro-, and 5 -iodo-deriv-atives of 5-fluorouracil have been prepared conventionally. The a-anomer of 5 -fluoro-5 -deoxyuridine has been synthesized from a 1,2-oxazoline derivative of 5-deoxy-5-fluoro-D-ribose, in turn prepared by a sulphonate displacement using pyridinium fluoride. Treatment of 1-(o-D-arabinofuranosyl)-uracil with diphenylcarbonate yielded the 1,4-oxazin derivative (23) which yielded the 2 -chloro-2 -deoxy-arabino-a-nucleoside (24) on chlorination this was then reduced to the 2 -deoxy analogue (25). 5-Fluorouridine has been... 

---