PYRIDINIUM CHLORIDE

1

Pyridinium Chloride

N

•HCl

[628-13-7]

C

5

H

6

ClN

(MW 115.57)

InChI = 1/C5H5N.ClH/c1-2-4-6-5-3-1;/h1-5H;1H
InChIKey = AOJFQRQNPXYVLM-UHFFFAOYAN

(cleavage of oxiranes to chlorohydrins;

3

cleavage of phenol

methyl ethers;

1,5

removal of N-trityl protecting groups;

6

catalyst

for Fischer indole synthesis

7

)

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 appar-

ent decomposition after several years of storage at room tem-
perature. The salt is very hygroscopic and must be protected
from moist air.

Cleavage of Oxiranes. The title reagent (1) reacts with a vari-

ety of cyclic and acyclic oxiranes to give chlorohydrins. Typically,
a 2:1 ratio of (1) to oxirane is employed and the reactions are car-
ried out at ambient temperature in chloroform or pyridine (eqs 1
and 2).

3

(1)

Ph

O

Ph

Cl

OH

(1), CHCl

3

rt, 4 h

87%

(1), CHCl

3

(2)

O

Cl

OH

rt, 1 h

75%

Cleavage of Phenol Methyl Ethers. Treatment of anisole with

3 equiv of (1) at 200–220

◦

C provides phenol (eq 3).

4

A modifica-

tion of the procedure is reported which allows for a more conve-
nient 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

(1),

∆

OMe

OH

(3)

83%

OMe

NO

2

CF

3

CF

3

NO

2

OH

OH

NO

2

(4)

(1),

∆

CO

2

H

HBr, HOAc

75%

or 6N KOH

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

The title reagent (1) catalyzes cleavage of trityl protecting groups
from the N-α 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).

(5)

(1), MeOH

Trt–His(Trt)–Lys(Boc)–CO

2

Me

H

2

N–His–Lys(Boc)–CO

2

Me

∆

Catalysis of the Fischer Indole Synthesis. Reagent (1) dis-

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

7

(6)

(1), py

N

O

CO

2

Et

N
H

N CO

2

Et

PhNHNH

2

+

∆

80%

1.

Prey, V., Chem. Ber. 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., Synth. Commun. 1981, 11,
287.

4.

Prey, V., Chem. Ber. 1941, 74, 1219.

5.

Filler, R.; Khan, B. T.; McMullen, C. W., J. Org. Chem. 1962, 27, 4660.

6.

Sieber, P.; Riniker, B., Tetrahedron Lett. 1987, 28, 6031.

7.

Welch, W. M., Synthesis 1977, 645.

Michael W. Wilson

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

Avoid Skin Contact with All Reagents