Reductive acylamination of pyridine N-oxide with ethylenediamine and phenylenediamines

Article abstract of DOI:10.1134/S1070428007110176

Reactions of pyridine N-oxide with ethylenediamine and o- and p-phenylenediamines in the presence of p-toluenesulfonyl chloride in alkaline medium lead to the formation of the corresponding N,N′-bis-(p- tolylsulfonyl)-N,N′-bis(pyridin-2-yl)diamines as a result of reductive acylamination.

Full text of DOI:10.1134/S1070428007110176

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 11, pp. 1696–1697. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © Yu.V. Kurbatov, M.A. Solekhova, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 11, pp. 1696–1697.
Reductive Acylamination of Pyridine N-Oxide
with Ethylenediamine and Phenylenediamines
Yu. V. Kurbatov and M. A. Solekhova
Alisher Navoi Samarkand State University, Universitetskii bul’var 15, Samarkand, 703004 Uzbekistan
Received March 2, 2006
Abstract—Reactions of pyridine N-oxide with ethylenediamine and o- and p-phenylenediamines in the pres-
ence of p-toluenesulfonyl chloride in alkaline medium lead to the formation of the corresponding N,N′-bis-
(p-tolylsulfonyl)-N,N′-bis(pyridin-2-yl)diamines as a result of reductive acylamination.
DOI: 10.1134/S1070428007110176
We previously reported on the reductive acylamina-
tion of pyridine N-oxide (I) with aromatic and hetero-
aromatic monoamines and their N-(p-tolylsulfonyl)
derivatives [1, 2] in the presence of p-toluenesulfonyl
chloride (II) as acylating agent. In continuation of
these studies we examined reactions of pyridine
N-oxide (I) with diamines, ethylenediamine (III) and
o- and p-phenylenediamines IV and V, under analo-
gous conditions. The reactions were carried out at
room temperature in a two-phase system (chloroform–
water) in the presence of p-toluenesulfonyl chloride
(II) and various bases (potassium and sodium hydrox-
ides and carbonates). The reaction of pyridine N-oxide
(I) with diamine III gave N,N′-bis(p-tolylsulfonyl)-
N,N′-bis(pyridin-2-yl)ethylenediamine (VI) in high
yield (88%). The fact that we failed to detect the cor-
responding monosubstituted derivative suggests inter-
mediacy of N,N′-bis(p-tolylsulfonyl)ethylenediamine
dianion C in the process (Scheme 1). Thus the ob-
served reaction may be regarded as a rare case of direct
formation of disubstituted product without isolation of
intermediate monosubstituted derivative.
Likewise, the reactions of pyridine N-oxide (I) with
aromatic diamines IV and V produced N,N′-bis-
(p-tolylsulfonyl)-N,N′-bis(pyridin-2-yl)benzene-1,2-
and -1,4-diamines VII and VIII in 65 and 66% yield,
respectively (Scheme 2). The lower yields of com-
pounds VII and VIII as compared to VI are likely to
result from reduced nucleophilicity of the correspond-
ing N-acyl anions, while similar reactivities of o- and
p-phenylenediamines may be rationalized in terms of
high reaction rate (reaction time 2 h). The structure of
VI–VIII was proved by their acid hydrolysis to the
corresponding N,N′-bis(pyridin-2-yl)diamines IX–XI.
Scheme 1.
TsCl (II)
Cl–
N
N
O
OTs
I
A
TsCl, OH–
TsCl, OH–
H2NCH2CH2NH2
H2NCH2CH2NHTs
TsNHCH2CH2NHTs
III
B
OH–
–H2O
OH–
B
[TsNCH2CH2NHTs]–
[TsNCH2CH2NTs]2–
–H2O
C
Ts
N
OTs
Ts
N
H2O, H+
–2TsOH
OH–
H
N
N
2A
+ B
N
N
N
N
–H2O
H
OTs Ts
Ts
VI
1696

REDUCTIVE ACYLAMINATION OF PYRIDINE N-OXIDE
1697
Scheme 2.
N,N′-Benzene-1,4-diylbis[N-(pyridin-2-yl)-4-tolu-
enesulfonamide] (VIII). A solution of 0.95 g
(10 mmol) of oxide I, 0.54 g (5 mmol) of diamine V,
and 5.7 g (30 mmol) of p-toluenesulfonyl chloride in
30 ml of chloroform was mixed with 30 ml of 10%
aqueous sodium hydroxide, and the mixture was stirred
for 2 h at 20°C. The mixture was treated as described
above to isolate 2.1 g (65%) of compound VIII,
mp 170°C (from ethanol). Found, %: N 9.7.
C30H28N4S2O4. Calculated, %: N 9.82.
H2O, H+
–2TsOH
X
X
N
N
N
N
N
N
N
N
H
H
Ts
Ts
VI–VIII
IX–XI
VI, IX, X = (CH2)2; VII, X, X = o-C6H4; VIII, XI, X = p-C6H4.
The described reactions attract interest from the
viewpoint of synthesis of substituted heteroaromatic
diamines. Compound IX was shown to exhibit trypa-
nocidal activity [3], while derivatives of XI possess
bactericidal properties [4].
Hydrolysis of amides VI–VIII. A solution of
1.7 mmol of compound VI–VIII in 5 ml of concen-
trated hydrochloric acid was heated for 21 h at the
boiling point. The mixture was evaporated to dryness,
the residue was washed with diethyl ether, and the sol-
vent was distilled off to isolate p-toluenesulfonic acid;
yield 88, 80, and 73%, respectively (mp 90–92°C; pub-
lished data [5]: mp 92°C). The material insoluble in
diethyl ether was dissolved in a minimal amount of
water, the solution was made alkaline by adding potas-
sium carbonate and extracted with chloroform, the
extract was dried over anhydrous sodium sulfate, the
solvent was distilled off, and the residue was recrystal-
lized from petroleum ether (bp 70–110°C).
EXPERIMENTAL
The progress of reactions and the purity of products
were monitored by paper chromatography (fast no. 2)
using butan-1-ol–hydrochloric acid–water (50:7:14 by
volume) as eluent; spots were detected by spraying
with the Dragendorff reagent.
N,N′-Ethane-1,2-diylbis[N-(pyridin-2-yl)-4-tolu-
enesulfonamide] (VI). A solution of 0.95 g (10 mmol)
of pyridine N-oxide (I), 0.25 g (5 mmol) of ethylene-
diamine (III), and 0.7 g (3.7 mmol) of p-toluene-
sulfonyl chloride in 25 ml of chloroform was mixed
with 30 ml of 10% aqueous sodium hydroxide, and
the mixture was stirred for 8 h at 20°C. Every 2 h,
a sample was withdrawn from the mixture and ana-
lyzed by paper chromatography as indicated above.
The mixture contained initial pyridine N-oxide I and
final product VI. The aqueous phase was separated and
repeatedly extracted with chloroform, the extracts were
combined with the organic phase and dried over an-
hydrous sodium sulfate, the solvent was distilled off,
and the residue was washed with hexane. Yield 2.1 g
(88%), mp 175–177°C (from ethanol). Found, %:
N 10.6. C26H26N4O4S2. Calculated, %: N 10.7.
N,N′-Bis(pyridin-2-yl)ethane-1,2-diamine (IX).
Yield 97%, mp 132–133°C; published data [3]:
mp 134–135°C.
N,N′-Bis(pyridin-2-yl)benzene-1,2-diamine (X).
Yield 80%, mp 164–165°C; published data [6]:
mp 167°C.
N,N′-Bis(pyridin-2-yl)benzene-1,4-diamine (XI).
Yield 70%, mp 199–200°C; published data [6]:
mp 200–201°C.
REFERENCES
1. Kurbatov, Yu.V. and Solekhova, M.A., Zh. Org. Khim.,
1983, vol. 19, p. 663.
N,N′-Benzene-1,2-diylbis[N-(pyridin-2-yl)-4-tolu-
enesulfonamide] (VII). A solution of 0.95 g (10 mmol)
of oxide I, 0.54 g (5 mmol) of diamine IV, and 3.8 g
(20 mmol) of p-toluenesulfonyl chloride in 30 ml of
chloroform was mixed with 30 ml of 10% aqueous
sodium hydroxide, and the mixture was stirred for 2 h
at 20°C. The mixture was treated as described above to
isolate 1.8 g (66%) of compound VII, mp 171–172°C
(from acetonitrile). Found, %: N 9.6. C30H26N4O4S2.
Calculated, %: N 9.82.
2. Kurbatov, Yu.V. and Solekhova, M.A., Khim. Geterotsikl.
Soedin., 1986, p. 936.
3. Sharp, T.M., J. Chem. Soc., 1938, p. 1191.
4. Thomas, K. and Jerchel, D., FRG Patent Appl.
no. 2606592, 1974; Chem. Abstr., 1977, vol. 87,
no. 167891z.
5. Dictionary of Organic Compounds, Heilbron, J. and Bun-
bury, H.M., Eds., London: Eyre and Spottswoode, 1953,
vol. 1.
6. Fischer, O., Ber., 1902, vol. 35, p. 3674.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 11 2007