Reaction of 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-diones with lithium aluminum hydride

Article abstract of DOI:10.1023/B:COHC.0000003519.63444.29

The corresponding 3,3,6,6,-tetramethyl-1,2,3,4,5,6,7,8-octahydroacridines have been obtained by the interaction of 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione, its 9-Ph- and 9-p-MeOC₆H₄-substituted derivative

Full text of DOI:10.1023/B:COHC.0000003519.63444.29

Chemistry of Heterocyclic Compounds, Vol. 39, No. 8, 2003
REACTION OF 3,3,6,6-TETRAMETHYL-
1,2,3,4,5,6,7,8,9,10-DECAHYDROACRIDINE-
1,8-DIONES WITH LITHIUM ALUMINUM HYDRIDE
A. N. Pyrko
The corresponding 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroacridines have been obtained by the
interaction of 3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione, its 9-Ph- and
9-p-MeOC6H4-substituted derivatives with lithium aluminum hydride. The reaction proceeds in boiling
diglyme and also at room temperature on extended stirring of the reactants in ether.
Keywords: decahydroacridine, reduction with lithium aluminum hydride.
The interaction of 3,5-diacylpyridines with complex metal hydrides (NaBH4, LiAlH4) proceeds with the
reduction of either the carbonyl functions to alcohols, or of the pyridine ring to a 1,4-dihydropyridine [1]. In
particular the reaction of octahydroacridinedione 1 (R = H) with NaBH4 proceeds with the reduction of the
pyridine ring and leads to decahydroacridine 2a [2], but its interaction with LiAlH4 leads to an
octahydroacridinediol 3 [3].
In a series of these compounds it seemed of interest to effect the reduction of the carbonyl functions of
decahydroacridinediones 2a-c with lithium aluminum hydride. It turned out that the reaction proceeds in boiling
diglyme and leads to octahydroacridines 4a-c. In addition the reaction may be also effected at room temperature
as was shown by us using the conversion of decahydroacridinedione 2b to octahydroacridine 4b as an example.
The reduction occurs on extended stirring of the components in ether.
O
R
O
OH
OH
LiAlH4
(R = H)
N
1
N
3
NaBH4
O
O
R
R
LiAlH4
N
4a–c
N
H
2a–c
1, 2, 4 a R = H, b R = Ph, c R = p-MeOC6H4
__________________________________________________________________________________________
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk 220141; e-mail:
labst@iboch.bas-net.by. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1181-1183,
August, 2003. Original article submitted August 7, 2000.
0009-3122/03/3908-1029$25.00©2003 Plenum Publishing Corporation
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TABLE 1. Spectral Characteristics of the Synthesized Compounds 4a-c
IR spectrum, UV spectrum,
Com-
pound
1H and 13C NMR spectra, δ, ppm (J, Hz)*
ν, cm-1
λmax, nm (log ε)
1435, 1460,
1578, 1610,
2930, 2875
210 (3.63),
281 (3.64)
0.98 (12H, s, CH3); 1.54 (4H, t, J = 7.0, 2- and 7-CH2);
2.62 (4Н, s, 4- and 5-CH2); 2.73 (4H, t,
4a
J = 7.0, 1- and 8-CH2); 7.10 (1H, s, 9-H)
[25.78 (С(2), С(7)); 28.72 (CH3); 30.63 (C(3), C(6));
36.01 (C(1), C(8)); 46.58 (C(4), C(5)); 128.20 (C(8a), C(9a));
137.48 (C(9)); 154.32 (C(4a), C(10a))]
0.99 (12H, s, CH3); 1.44 (4H, t, J = 7.0, 2- and 7-CH2);
2.38 (4H, t, J = 7.0, 1-, 8-H2); 2.74 (4H, s, 4- and
5-CH2); 7.08 (2H, d, J = 7.0, 8'- and 5'-H);
7.41 (3H, m, 2'-, 4'- and 6'-H)
1440, 1470,
1555, 1572,
2872, 2920
282 (3.71)
4b
[24.40 (C(2), C(7)); 28.07 (CH3); 29.87 (C(3), C(6));
35.56 (C(1), C(8)); 46.68 (C(5), C(4)); 125.70 (C(8a), C(9a));
127.15 (C(2'), C(6')); 127.85 (C(4')); 128.71 (C(3'), C(5'));
138.71 (C(1')); 149.16 (C(9)); 153.76 (C(4a), C(10a))]
0.98 (12H, s, CH3); 1.46 (4H, t, J = 7.0, 2- and 7-CH2);
2.35 (4H, t, J = 7.0, 1- and 8-CH2); 2.72 (4H, s, 4- and
5-CH2); 3.88 (3H, s, OCH3); 6.78 (2H, d, J = 8.0,
2'- and 6'-H); 6.90 (2H, d, J = 8.0, 3'- and 5'-H)
1445, 1520,
1580, 1620,
2875, 2950
222 (4.08),
282 (3.77)
4c
[24.46 (C(2), C(7)); 28.02 (CH3); 29.62 (C(3), C(6));
35.56 (C(1), C(8)); 46.08 (C(4), C(5)); 55.20 (OCH3);
114.16 (C(3'), C(5')); 126.58 (C(8a), C(9a));
128.95 (C(2'), C(6')); 130.62 (C(1')); 149.47 (C(9));
153.56 (C(4a), C(10a)); 158.71 (C(4'))]
_______
* The 13C NMR spectra are given in square brackets.
The structures of compounds 4a-c were confirmed by spectral data and the results of elemental analysis
1
(Table 1). In the H NMR spectra there was a singlet signal for the protons of the four methyl groups at 0.98,
0.99, and 0.98 ppm, a triplet signal for the methylene protons in positions 2 and 7 (1.54, 1.44, and 1.46 ppm)
and the methylene protons interacting with them in positions 1 and 8 (2.73, 2.38, and 2.36 ppm), and also a
singlet signal for the methylene protons at positions 4 and 5 (2.62, 2.74, and 2.72 ppm). In the 13C NMR
spectrum it was possible to assign all the signals unequivocally (Table 1).
It should be noted that the conversion described is an efficient method of transition from the Hantzsch
synthesis products to pyridine derivatives containing no oxygen functions.
EXPERIMENTAL
A check on the synthesis and on the homogeneity of the compounds obtained was effected by TLC on
Silufol UV 254 plates, eluent ether–hexane, 1:2. Visualization was with UV light or iodine vapor. Melting
points were determined on a Boetius stage. The IR spectra were recorded on a UR-20 instrument in KBr disks.
1
The UV spectra were taken on a Specord M-400 spectrometer for solutions in ethanol. The H and 13C NMR
13
spectra were recorded in CDCl3 on a Bruker AC-200 instrument (200 and 50 MHz respectively). The C NMR
spectra were obtained with decoupling from protons.
Decahydroacridinediones 2a-c were obtained by the procedures of [2,4,5].
3,3,6,6-Tetramethyl-9-phenyl-1,2,3,4,5,6,7,8-octahydroacridine (4b). A. Decahydroacridinedione 2b
(698 mg, 2 mmol) in anhydrous diglyme (10 ml) was boiled with lithium aluminum hydride (300 mg, 7.9 mmol)
for 1.5 h. After cooling water (2 ml) and ethanol (50 ml) were added carefully to the reaction mixture. The solid
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was filtered off, the filtrate evaporated, the residue was treated with water (20 ml), ether (200 ml), and the ether
solution dried over MgSO4. After evaporation of the ether and crystallization of the residue from ether–hexane,
1:1, hydroacridine 4b (510 mg: 80%) was obtained; mp 178-180°C (ether–hexane). Found, %: C 86.61; H 9.18;
N 4.50. C23H29N. Calculated, %: C 86.52; H 9.09; N 4.39.
3,3,6,6-Tetramethyl-1,2,3,4,5,6,7,8-octahydroacridine (4a) was obtained analogously with a yield of
330 mg (68%) from decahydroacridinedione 2a (546 mg, 2 mmol); mp 96-98°C (ether–hexane). Found, %:
C 83.76; 10.17; 5.88. C17H25N. Calculated, %: C 83.95; H 10.29; N 5.76.
9-(4-Methoxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8-octahydroacridine (4c) was obtained with a
yield of 565 mg (81%) from decahydroacridinedione 2c (758 mg, 2 mmol); mp 230-235°C (decomp., ethyl
acetate–hexane). Found, %: C 82.36; H 8.94; N 4.12. C24H31N. Calculated, %: C 82.52; H 8.88; N 4.01.
A. Decahydroacridinedione 2b (698 mg, 2 mmol) in dry ether (200 ml) was stirred with lithium
aluminum hydride (300 mg, 7.9 mmol) at room temperature for 15 h. Water (0.5 ml) was then carefully added
and stirring continued for a further 5 h. Water (5 ml) was added carefully and the reaction mixture filtered
through a layer (2 cm) of dry Na2SO4. After evaporation and crystallization of the residue from ether–hexane,
1:1 the hydroacridine 4b (490 mg, 77%) was obtained.
REFERENCES
1.
2.
3.
4.
5.
E. Klingsberg (editor), Pyridine and Its Derivatives, Vol. 3, Interscience, New York (1962), p. 200.
E. I. Stankevich and G. Ya. Vanag, Izv. Akad. Nauk LatvSSR, 223 (1961).
A. N. Pyrko, Khim. Geterotsikl. Soedin., 774 (1999).
A. A. Bakibaev and V. D. Filimonov, Zh. Org. Khim., 25, 1579 (1989).
G. Ya. Vanag and E. I. Stankevich, Zh. Obshch. Khim., 30, 3287 (1960).
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