Pyridinium Chloride

[628-13-7]  · C5H6ClN  · Pyridinium Chloride  · (MW 115.57)

(cleavage of oxiranes to chlorohydrins;3 cleavage of phenol methyl ethers;1,5 removal of N-trityl protecting groups;6 catalyst for Fischer indole synthesis7)

Alternate Name: pyridine hydrochloride.

Physical Data: mp 144 °C (dec).

Solubility: sol water, chloroform, ethanol; insol ethyl ether.

Form Supplied in: white hygroscopic crystalline solid.

Preparative Method: precipitates as a 98% yield of 99.8% pure white crystals when Hydrogen Chloride gas is passed through a solution of Pyridine in ether.1,2

Purification: recrystallize from chloroform/ethyl acetate and wash with ethyl ether. Can be dried by refluxing in benzene with azeotropic removal of water.

Handling, Storage, and Precautions: stable solid, with no apparent decomposition after several years of storage at room temperature. The salt is very hygroscopic and must be protected from moist air.

Cleavage of Oxiranes.

The title reagent (1) reacts with a variety of cyclic and acyclic oxiranes to give chlorohydrins. Typically, a 2:1 ratio of (1) to oxirane is employed and the reactions are carried out at ambient temperature in chloroform or pyridine (eqs 1 and 2).3

Cleavage of Phenol Methyl Ethers.

Treatment of anisole with 3 equiv of (1) at 200-220 °C provides phenol (eq 3).4 A modification of the procedure is reported which allows for a more convenient in situ preparation of (1).5 The use of the title reagent to cleave phenol methyl ethers avoids the strong acidic or basic conditions of alternative methods. This has found utility in the cleavage of substrates with acid- or base-sensitive moieties (eq 4).5

Cleavage of N-a- and N-τ-Trityl Groups from Histidine.

The title reagent (1) catalyzes cleavage of trityl protecting groups from the N-a position of histidine, as well as the N-τ position on the imidazole moiety of histidine.6 In a typical reaction, the trityl group is cleaved with 5% of (1) in MeOH at 60 °C. It appears to have application in orthogonal peptide protection schemes. Boc and Fmoc protecting groups are unaffected under these conditions (eq 5).

Catalysis of the Fischer Indole Synthesis.

Reagent (1) displays utility as a mild catalyst for the Fischer indole synthesis of substrates with strong acid sensitivity (eq 6).7

1. Prey, V. CB 1942, 75, 445.
2. Taylor, M. D.; Grant, L. R. J. Chem. Educ. 1955, 32, 39.
3. Loreto, M. A.; Pellacani, L.; Tardella, P. A. SC 1981, 11, 287.
4. Prey, V. CB 1941, 74, 1219.
5. Filler, R.; Khan, B. T.; McMullen, C. W. JOC 1962, 27, 4660.
6. Sieber, P.; Riniker, B. TL 1987, 28, 6031.
7. Welch, W. M. S 1977, 645.

Michael W. Wilson

Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA

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