Arylaliphatic 3-aza-1,5-diketones: Reactions with N-nucleophiles

Article abstract of DOI:10.1023/B:RUJO.0000010226.45434.ab

1-Substituted 3,5-diphenylpyrazinium salts were obtained by reactions of tertiary bis(phenacyl)-amines with ammonium acetate, hydroxylamine hydrochloride, and hydrazine hydrate in acid medium. The reaction of quaternary dimethylbis(phenacyl)ammonium bromi

Full text of DOI:10.1023/B:RUJO.0000010226.45434.ab

Russian Journal of Organic Chemistry, Vol. 39, No. 9, 2003, pp. 1346 1348. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 9, 2003,
pp. 1418 1420.
Original Russian Text Copyright
2003 by Akimova, Trofimenko, Ivanenko.
Arylaliphatic 3-Aza-1,5-diketones:
Reactions with N-Nucleophiles
T. I. Akimova, N. N. Trofimenko, and Zh. A. Ivanenko
Far East State University, ul. Oktyabr’skaya 27, Vladivostok, 690600 Russia
e-mail: tiakim@chem.dvgu.ru
Received February 12, 2003
Abstract 1-Substituted 3,5-diphenylpyrazinium salts were obtained by reactions of tertiary bis(phenacyl)-
amines with ammonium acetate, hydroxylamine hydrochloride, and hydrazine hydrate in acid medium. The
reaction of quaternary dimethylbis(phenacyl)ammonium bromide with hydrazine hydrate afforded 3,6-di-
phenylpyridazine.
Bis(phenacyl)amines like I III have been reported
for the first time at the beginning of the past century
1]. Gabriel [1] studied the reaction of bromoaceto-
nium perchlorates IV VI (Scheme 1). It should be
noted that we have found no published data on such
pyrazinium salts.
[
phenone with ammonia and obtained bis(phenacyl)-
amine (R = H) which was then brought into reaction
with ammonia in alcoholic solution. The structure of
the resulting cyclization product was refined later [2]
as 2,6-dihydropyrazine.
While studying the chemistry of 1,5-diketones,
we turned to their 3-aza analogs, among which the
simplest and most accessible were bis(phenacyl)-
amines I III. However, these compounds appeared
to be studied very poorly, though they attract a certain
interest, in particular as initial compounds for the
synthesis of heterocycles with two heteroatoms. There
are some published data on the preparation from such
diketones of oxazine [3] and dihydropyrazine deriva-
tives [4]. The latter were obtained via reaction with
amines in toluene. It should be noted that common
In the reaction with ammonium acetate in acetic
acid, no effect of the R substituent on the rate of the
process was observed: in all cases the reaction was
complete in 2 h. With the other nucleophiles in alco-
holic medium, the reaction was the most difficult to
occur with diketone II (5 8 h); the process was more
ready in the case of diketone I (3 4 h), and the fastest
reaction was that with diketone III (20 min). In the
latter case, the reason is not the substituent effect but
poor solubility of product VI which precipitates from
the reaction mixture during the process.
The structure of the products was confirmed by the
1
IR, H NMR, and mass (HPLC MS) spectra. Unlike
Scheme 1.
1,5-diketones are known to react with N-nucleophiles
to give a variety of products [5]. Depending on the
conditions, dihydropyridine or pyridine derivatives,
pyridinium salts, or mixtures of these compounds
could be obtained.
Using compounds I III as examples (diketone I
was taken as the corresponding salt with perchloric
acid, and amines II and III were free bases), we
examined their reactions with ammonia and its deriva-
tives, namely with ammonium acetate in acetic acid
and with hydroxylamine hydrochloride and hydrazine
hydrate in isopropyl alcohol in the presence of per-
chloric acid. Regardless of the N-nucleophile, com-
pounds I III gave rise to the same products, pyrazi-
I, IV, R = Me; II, V, R = Ph; III, VI, R = p-MeOC H ;
6
4
X = H, OH, NH2.
1
070-4280/03/3909-1346$25.00 2003 MAIK Nauka/Interperiodica

ARYLALIPHATIC 3-AZA-1,5-DIKETONES:
1347
Scheme 2.
initial 3-aza-1,5-diketones I III, the IR spectra of
frequency 250 MHz) from solutions in DMSO-d with
6
products IV VI lack carbonyl absorption (1685
addition of tetramethylsilane as internal reference.
The mass spectra of compounds IV VI were recorded
on an HP 1100 LS/MSD HPLC MS system, and of
VIII, on an Agilent 5973N GC MS system (HP5-ms
column; carrier gas helium, flow rate 1 ml/min;
detector temperature 280 C). The progress of the
reactions was monitored by TLC using Sorbfil as
sorbent and ethanol as eluent and by IR spectroscopy
(following disappearance of the carbonyl absorption
band in the spectrum of the reaction mixture).
1
1
689 cm ) but contain absorption bands belonging to
stretching vibrations of the aromatic fragments (1600
1
1
1
500 cm ) and perchlorate ion (a strong band at
1
1
088 1094 cm ). In the H NMR spectra (DMSO-d )
6
we observed signals from aromatic protons at 7.3
.5 ppm and a singlet at 9.8 ppm (2H), which was
8
assigned to protons of the pyrazinium ring [6].
1
Compounds IV and VI also showed in the H NMR
spectra singlets from the methyl and methoxy groups,
respectively, at
4.49 and 3.94 ppm.
1
-Substituted 3,5-diphenylpyrazinium salts
The molecular weights of cations IV VI deter-
mined from the mass spectra (HPLC MS) were in
agreement with the calculated values.
IV VI. a. Reaction with ammonium acetate. A mix-
4
ture of 0.3 g (8.2 10 mol) of diketone I perchlorate,
0.19 g (24.5 10 4 mol) of ammonium acetate, and
2
ml of glacial acetic acid was heated for 2 h under
We also examined the reactions of quaternary salt
VII with the same nucleophiles under analogous
conditions. It might be expected that the reaction
would stop at the stage of formation of dihydropyra-
zine A. However, such compounds were not isolated.
The reaction of VII with hydrazine hydrate in the
absence of an acid afforded 3,6-diphenylpyridazine
VIII. This result may be explained by the occurrence
of Stevens rearrangement by the action of a base
reflux. The mixture was cooled, and the precipitate of
IV was filtered off and washed with 50% ethanol.
Yield 0.12 g. An additional 0.08 g of the product was
isolated from the filtrate by adding 1 ml of a saturated
solution of NH ClO . Recrystallization from acetic
4
4
acid gave 0.17 g (60.7%) of salt IV. The reactions
with diketones II and III taken as free bases were
carried out in a similar way. The mixture was cooled
to room temperature, and 1 ml of a saturated solution
of ammonium perchlorate was added. The solution
was separated from tarry material by decanting, and
the latter was ground with water to obtain a powder
which was filtered off. Recrystallization gave 0.21 g
(
NH NH ). As shown in [7], phenacylammonium salts
2 2
readily undergo Stevens rearrangement to give bis-
aroylethenes even by the action of an amine. Presum-
ably, in our case intermediate diketone C reacts with
hydrazine hydrate with formation of compound VIII.
The structure of the product was confirmed by the IR
and GC MS data. Its melting point coincided with
that given in [8].
(57%) of V or 0.28 g (80%) of VI.
b. Reaction with hydroxylamine hydrochloride.
4
A mixture of 0.3 g (8.2 104 mol) of diketone I per-
chlorate, 0.28 g (40.8 10 mol) of hydroxylamine
hydrochloride, and 5 ml of isopropyl alcohol was
heated to the boiling point, and 65% perchloric acid
was added to pH 3 4. The mixture was heated for 3 h
under reflux and cooled, and the precipitate of IV was
filtered off and washed with isopropyl alcohol. Yield
0.2 g. Recrystallization from methanol afforded 0.18 g
(64%) of the product. The reactions with compounds
EXPERIMENTAL
The IR spectra were recorded on a Perkin Elmer
Spectrum BX-II spectrophotometer from samples
pelleted with KBr (compounds IV VI) or dispersed
1
in mineral oil (VIII). The H NMR spectra were
obtained on a Bruker AC-250 spectrometer (operating
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 9 2003

1
348
AKIMOVA et al.
II and III were carried out in a similar way. The
mixture was heated under reflux for 5 h (with II) or
OCH ); 7.38 d (2H), 7.72 m (6H), 8.09 d (2H), and
3
8.52 m (4H) (C H ); 9.8 s (2H, pyrazine). Mass spec-
6
5
+
2
0 min (III). The yields of salts V and VI were 49%
trum, m/z: 339 [M] ; calculated for the cation: 339.
and 50%, respectively.
Found, %: C 62.68; H 4.51; N 6.52. C H ClN O .
2
3
19
2
5
Calculated, %: C 62.94; H 4.33; N 6.38.
c. Reaction with hydrazine hydrate. A mixture of
4
0
(
.3 g (8.2 10 mol) of diketone I perchlorate, 0.2 g
3,6-Diphenylpyridazine (VIII). A mixture of
25 10 4 mol) of hydrazine hydrate, and 5 ml of
0.35 g (9 10 4 mol) of compound VII in 6 ml of
4
isopropyl alcohol was acidified to pH 3 4 by adding
perchloric acid. The mixture was heated for 4 h under
reflux and cooled, and the precipitate of salt IV was
filtered off and washed with isopropyl alcohol. Yield
ethanol and 0.1 g (10 10 mol) of hydrazine hydrate
was heated under reflux for 4 h. The mixture was
cooled, and the precipitate was filtered off and washed
with ethanol. Yield 0.15 g (30%). mp 220 222 C
(from ethanol); published data [8]: mp 225 C. IR spe-
0
.37 g [after recrystallization, 0.24 g (86%)]. The
1
reactions with compounds II and III were carried out
in a similar way: the mixture was heated under reflux
for 8 h (II) or 20 min (III); yield 68% (V), 61% (VI).
ctrum, , cm : 1582, 1548 (C Carom). Mass spec-
+
trum, m/z (I , %): 232 (42) [M] , 204 (10.2), 102
rel
(100), 76 (14). Found, %: C 82.93; H 5.25; N 12.28.
C H N . Calculated, %: C 82.76; H 5.17; N 12.07.
1
-Methyl-3,5-diphenylpyrazinium perchlorate
16 12
2
M 232.
(
IV). Beige crystals, mp 269 271 C. IR spectrum, ,
1
cm : 1624, 1600, 1548, 1508 (C Carom); 1276, 1238
(
1
REFERENCES
C N); 1090 (ClO ). H NMR spectrum, , ppm:
4
4
.49 s (3H, CH ); 7.72 t (6H) and 8.37 m (4H)
3
1
.
Lellmann, E. and Donner, A., Ber., 1890, vol. 23,
p. 166; Gabriel, S., Ber., 1914, vol. 46, p. 3859.
(C H ); 9.7 s (2H, pyrazine). Mass spectrum, m/z:
6 5
+
2
47 [M] ; calculated for the cation: 247. Found, %:
2
3
.
.
Tutin, F., J. Chem. Soc., 1910, vol. 97, p. 2501.
C 58.64; H 4.42; N 8.24. C H ClN O . Calculated,
1
7
15
2
4
Correia, J., J. Org. Chem., 1973, vol. 38, no. 19,
p. 3433.
%
: C 58.87; H 4.33; N 8.08.
1
,3,5-Triphenylpyrazinium perchlorate (V).
4
.
Fourrey, J.L., J. Chem. Soc., Perkin. Trans. 1, 1987,
p. 1841.
Light brown crystals, mp 249 250 C (from methanol).
IR spectrum, , cm : 1608, 1523, 1489 (C Carom);
1
1
1
276, 1205 (C N); 1093 (ClO ). H NMR spectrum,
5. Moskovkina, T.V., Kaminskii, V.A., Vysotskii, V.I.,
4
,
ppm: 7.72 t (6H), 7.86 t (3H), 8.12 m (2H), and
and Tilichenko, M.N., Khim. Geterotsikl. Soedin.,
1
973, no. 6, p. 826; Kaminskii, V.I., Doctoral (Chem.)
8.54 m (4H) (C H ); 9.89 s (2H, pyrazine). Mass spe-
6
5
+
Dissertation, Riga, 1986.
ctrum, m/z: 309 [M] ; calculated for the cation: 209.
Found, %: C 64.35; H 4.32; N 7.14. C H ClN O .
6. Kazantseva, I.V., Charushin, V.N., Chupakhin, O.N.,
Chernyshev, A.I. and Esepov, S.E., Khim. Geterotsikl.
Soedin., 1985, no. 9, p. 1257.
2
2
17
2
4
Calculated, %: C 64.63; H 4.16; N 6.85.
-p-Methoxyphenyl-3,5-diphenylpyrazinium
perchlorate (VI). Green crystals, mp 246 248 C
1
7. Heffe, W. and Krohnke, F., Chem. Ber., 1956, vol. 89,
1
p. 822.
(
1
(
from methanol DMF, 10:1). IR spectrum, , cm :
590, 1520, 1505 (C Carom); 1267 (C N); 1089
8. Baranger, H. and Levisalles, J., Bull. Soc. Chim. Fr.,
1
ClO ). H NMR spectrum, , ppm: 3.94 s (3H,
1957, p. 704.
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 9 2003