Formation of the pyrroline N-oxide ring by interaction of α-isonitrosoketones-derivatives of tetrahydrobenzofurazan and -furoxan with aldehydes and morpholine and some of the reactions of these compounds

Article abstract of DOI:10.1007/s10593-005-0081-z

α-Isonitroso ketones, derivatives of tetrahydrobenzofurazan and furoxan, react with aldehydes (acetaldehyde and propionaldehyde) and morpholine to form derivatives of tetrahydropyrrolo[2,3-e]-2,1,3-benzoxadiazole 6-oxide. Treatment of the latter with hydrazine hydrate gave derivatives of 4,5-dihydro-1,2,5-oxadiazolo[3,4-f]cinnoline which are readily dehydrogenated with tetrachloro-benzoquinone to derivatives of 1,2,5-oxadiazolo[3,4-f] cinnoline. Reduction of tetrahydropyrrolo[2,3-e]-2,1,3-benzoxadiazole 6-oxides with sodium borohydride gave derivatives of N-hydroxyhexahydro-pyrrolo[2,3-e]-2, 1,3-benzoxazole.

Full text of DOI:10.1007/s10593-005-0081-z

Chemistry of Heterocyclic Compounds, Vol. 40, No. 11, 2004
EFFICIENT ROUTE TO SUBSTITUTED
2-AMINOQUINOLINE
V. D. Dyachenko and A. G. Kudryavtseva
Keywords: 1,3-aminophenol, 4-hydroxyphenylmethylene cyanothioacetamide, substituted 2-amino-
quinoline, acylation, Michael reaction.
1,3-Aminophenol undergoes a Michael addition to 4-hydroxyphenylmethylene malononitrile followed
by intramolecular cyclization to form substituted 2,7-diamino-4H-benzo[b]pyran [1]. We observed that reacting
4-hydroxyphenylmethylene cyanothioacetamide (2) with 1,3-aminophenol 1 in ethanol in the presence of
morpholine leads to formation of 2-amino-3-cyano-7-hydroxy-4-(4-hydroxyphenyl)quinoline (3). Thus
1,3-aminophenol 1 does not initially add to activated alkene 2 at the 6 position, which would lead to the
corresponding pyran, but rather to position 4 with formation of the Michael adduct 4. The latter, when treated
with morpholine, even at room temperature undergoes intramolecular cyclization to form substituted
2-aminoquinoline 3. Refluxing it in acetic anhydride allows us to obtain the corresponding tetraacyl derivative 5,
which is promising for drug discovery [2].
OH
OH
CN
HO
NH
2
CN
NH
..
NH
1
S
NH
2
HO
S
2
2
2
4
OH
OAc
Ac O
2
CN
CN
NH
–H S,
2
–2[H]
AcO
N
N(Ac)
HO
N
2
2
5
3
The 1H NMR spectra were taken on a Bruker DR-500 (500 MHz) in DMSO-d6.
__________________________________________________________________________________________
Taras Shevchenko Lugansk State Pedagogical University, Lugansk 91011, Ukraine; e-mail:
dvd-lug@online.lg.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1728-1729,
November, 2004. Original article submitted September 8, 2004.
0009-3122/04/4011-1495©2004 Springer Science+Business Media, Inc.
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2-Amino-3-cyano-7-hydroxy-4-(4-hydroxyphenyl)quinoline (3). Yield 76%; mp 198-200°C (EtOH).
IR spectrum (vaseline oil), ν, cm-1: 3304, 3420, 3495 (NH2, OH); 2218 (C≡N); 1673 (δNH2). 1H NMR spectrum,
δ, ppm (J, Hz): 11.32 and 10.11 (1H each, both br. s, 2OH); 8.21 (2H, br. s, NH2); 7.34 (3H, m, Harom); 7.06 (1H,
s, H-8); 6.98 (3H, m, Harom). Mass spectrum, m/z (Irel, %): 278 [M+1]+ (27), 277 [M]+ (100), 260 (12), 249 (25).
Found, %: C 69.14; H 3.82; N 15.36. C16H11N3O2. Calculated, %: C 69.31; H 4.00; N 15.15.
7-Acetoxy-3-cyano-2-diacetylamino-4-(4-acetoxyphenyl)quinoline (5). Yield 70%; mp 168°C
(AcOH). IR spectrum (vaseline oil), ν, cm-1: 2216 (C≡N); 1694 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 7.95
(1H, s, H-8); 7.88 (1H, d, J = 9.30, H-6); 7.70 (2H, d, J = 7.74, H-3 and H-5 Ar); 7.68 (1H, d, J = 9.30, H-5);
7.48 (2H, d, J = 7.74, H-2 and H-6 Ar); 2.35 (12H, s, 4CH3). Mass spectrum, m/z (Irel, %): 445 [M]+ (6), 403
(29), 388 (25), 361 (32), 346 (41), 319 (40), 304 (42), 277 (43), 43 [Ac]+ (100). Found, %: C 64.61; H 4.12;
N 9.50. C24H19N3O6. Calculated, %: C 64.72; H 4.30; N 9.43.
REFERENCES
1.
2.
G. V. Klokol, L. G. Sharanina, V. N. Nesterov, V. E. Shklover, Yu. A. Sharanin, and Yu. T. Struchkov,
Zh. Org. Khim., 23, 412 (1987).
D. Barton and W. D. Ollis (editors), Comprehensive Organic Chemistry [Russian translation], Khimiya,
Moscow (1985), Vol. 8, p. 196.
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