Synthesis of 14 h-naphtho[1′,2′:5,6][1,3]oxazino-[3,2-a] benzimidazole, a new heterocyclic system

Article abstract of DOI:10.1007/s10593-011-0727-y

The previously unreported 14 H-naphtho[1′,2′:5,6][1,3] oxazino[3,2-a]benzimidazole heterocyclic system was synthesized by the condensation of 1-dimethylaminomethyl-2-naphthols and 2-methyl- sulfanylbenzimidazole. A highly reactive o-methylenequinone deriv

Full text of DOI:10.1007/s10593-011-0727-y

Chemistry of Heterocyclic Compounds, Vol. 47, No. 1, April, 2011 (Russian Original Vol. 47, No. 1, January, 2011)
SYNTHESIS OF 14H-NAPHTHO[1',2':5,6][1,3]OXAZINO-
[3,2-a]BENZIMIDAZOLE, A NEW HETEROCYCLIC SYSTEM
V. A. Osyanin1*, D. V. Osipov1, and Yu. N. Klimochkin1
The previously unreported 14H-naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazole heterocyclic
system was synthesized by the condensation of 1-dimethylaminomethyl-2-naphthols and 2-methyl-
sulfanylbenzimidazole. A highly reactive o-methylenequinone derivative of naphthalene is proposed as
an intermediate in this reaction.
Keywords: 2-methylsulfanylbenzimidazole, o-methylenequinones, 14H-naphtho[1',2':5,6][1,3]oxazino-
[3,2-a]benzimidazoles, Mannich bases, cascade reactions.
-Methylenequinones, which contain both electrophilic and nucleophilic sites, are valuable starting
reagents in heterocyclization reactions [1]. The driving force in these reactions is aromatic stabilization
following 1,4-addition of nucleophilic agents under Michael reaction conditions. In the case of good leaving
groups, the initially formed adducts undergo subsequent cyclization to give benzocondensed heterocyclic
systems [2, 3].
R1
R1
NMe2
OH
N
SMe
N
H
DMF
O
– NHMe2
R
R
1a–d
H
N
N
N
SMe
Me
S
N
O
O
N
N
OH
R1
R1
R1
– MeSH
2a–d
R
R
R
1, 2 a–c R = H, a R1 = H, b R1 = Ph, c R1 = 4-МеOC6H4; d R = 1-adamantyl, R1 = H
_______
* To whom correspondence should be addressed, e-mail: vosyanin@mail.ru.
1Samara State Technical University, 244 Molodogvardeiskaya Str., Samara 443100, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 136-139, January, 2011. Original
article submitted September 26, 2010.
108
0009-3122/11/4701-0108©2011 Springer Science+Business Media, Inc.

We have shown that 14H-naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazoles 2a-d, which are
representatives of a new heterocyclic system, can be obtained by heating naphthalene Mannich bases 1a-d with
2-methylsulfanylbenzimidazole in DMF at reflux in the presence of potassium carbonate. This is a cascade
reaction, proceeding in several steps: 1) a retro-Michael reaction with formation of the corresponding
o-methylenequinone from the Mannich base; 2) 1,4-addition of 2-methylsulfanylbenzimidazole to o-methyl-
enequinone, and 3) intramolecular nucleophilic replacement of the methylsulfanyl group.
The IR spectrum of products 2a-d lack the OH group stretching band, which indicates a cyclic structure
1
for these compounds. The H NMR spectra of 2a,d show methylene protons at 5.13-5.17 ppm. The signals for
the aliphatic methine protons in 2b,c are shifted strongly downfield and appear at 6.79-6.88 ppm.
EXPERIMENTAL
1
The IR spectra were taken on a Shimadzu FTIR-8400S spectrometer in KBr pellets. The H and 13C
NMR spectra were taken on a JEOL JNM-ECX400 spectrometer at 400 and 100 MHz, respectively, in CDCl3
with TMS as the internal standard. The mass spectra were obtained on a Finnigan Trace DSQ mass
spectrometer. The ionizing electron energy was 70 eV. The elemental analysis was carried out on a EuroVector
EA-3000 automatic CHNS analyzer.
Starting Mannich bases 1a-c were obtained from 2-naphthol according to reported procedures [4-6].
6-(1-Adamantyl)-1-dimethylaminomethyl-2-naphthol (1d). 33% Aqueous dimethylamine (3 ml,
20 mmol) and 37% aqueous formaldehyde (1.5 ml, 20 mmol) were added to a solution of 6-(1-adamantyl)-
2-naphthol [7] (5 g, 18 mmol) in ethanol (50 ml). The mixture was heated to reflux, cooled, and maintained for
20 h at 25°C and 48 h at -15°C. The precipitate formed was filtered off, washed with cold methanol, and
recrystallized from ethanol-DMF to give 6.1 g (83%) 1d as colorless crystals, mp 177-179°C (dec.). IR
spectrum, , cm-1: 3051 (OH), 2908, 2885, 2850 (CH Ad), 1604 (C=C), 1512, 1423, 1338, 1276, 1149, 844 (CH
arom). 1H NMR spectrum, , ppm (J, Hz): 1.77-1.85 (6H, m, 3CH2 Ad); 1.96-2.04 (6H, m, 3CH2 Ad); 2.14 (3H,
br. s, 3CH Ad); 2.41 (6H, s, 2CH3); 4.09 (2H, s, CH2); 7.08 (1H, d, J = 8.70, H arom); 7.53 (1H, dd, J = 8.70,
J = 1.83, H-7 arom); 7.65 (1H, d, J = 1.83, H-5 arom); 7.67 (1H, d, J = 8.70, H arom); 7.78 (1H, d, J = 8.70, H
arom); 9.91 (1H, br. s, OH). 13C NMR spectrum, , ppm: 29.07 (3CH Ad); 36.01 (C Ad); 36.97 (3CH2 Ad);
43.24 (3CH2 Ad); 44.79 (2CH3); 57.95 (CH2); 111.30 (C); 119.13 (CH); 120.87 (CH); 123.98 (CH); 124.48
(CH); 128.55 (C); 129.30 (CH); 130.81 (C); 145.29 (C); 156.34 (C). Mass spectrum, m/z (Irel, %): 335 [M]+ (2),
290 [M-NH(CH3)2] (30), 214 (66), 202 (32), 165 (30), 152 (32), 135 [Ad]+ (34), 44 (100). Found, %: C 82.39;
H 8.67; N 4.21. C23H29NO. Calculated, %: C 82.34; H 8.71; N 4.18.
14H-Naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazole (2a). A mixture of 2-methylsulfanylbenz-
imidazole (1 g, 6.1 mmol), Mannich base 1a (1.22 g, 6.1 mmol), and potassium carbonate (2.5 g, 18 mmol) in
DMF (15 ml) was heated at reflux with stirring for 4 h, cooled, and poured into cold water (50 ml). The
precipitate formed was filtered off, washed with water, dried, and recrystallized from DMF to give 1.11 g (67%)
benzimidazole 2a as colorless crystals, mp 216-218°C. IR spectrum, , cm-1: 3055 (CH arom), 2912, 1628
1
(C=N), 1539, 1516, 1454, 1304, 1288, 1254, 1219, 1072, 980, 814, 741. H NMR spectrum, , ppm (J, Hz):
5.13 (2H, s, CH2); 7.19-7.30 (4H, m, H arom); 7.39 (1H, ddd, J = 8.24, J = 6.41, J = 1.37, H arom); 7.53-7.63
(3H, m, H arom); 7.72-7.74 (2H, m, H arom). 13C NMR, , ppm: 40.44 (CH2); 106.58 (C); 108.55 (CH); 117.55
(CH); 118.62 (CH); 121.41 (CH); 121.70 (CH); 123.04 (CH); 125.59 (CH); 127.08 (CH); 128.81 (CH); 129.69
(C); 130.13 (CH); 130.43 (C); 132.12 (C); 139.77 (C); 146.01 (C); 150.24 (C). Mass spectrum, m/z (Irel, %): 272
[M]+ (74), 271 [M-H]+ (100), 243 (30), 127 (23), 44 (57). Found, %: C 79.45; H 4.39; N 10.34. C18H12N2O.
Calculated, %: C 79.39; H 4.44; N 10.29.
109

14-Phenyl-14H-naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazole (2b) was obtained in 75% yield
analogously to 2a (1.59 g) from 2-methylsulfanylbenzimidazole (1 g, 6.1 mmol), Mannich base 1b (1.69 g,
6.1 mmol), and potassium carbonate (2.5 g, 18 mmol) in DMF (15 ml) as colorless crystals, mp 218-220°C
(benzene). IR spectrum, , cm-1: 3055 (CH arom), 2924, 1624 (C=N), 1543, 1516, 1474, 1450, 1285, 1258,
1219, 829, 733, 702. 1H NMR spectrum, , ppm (J, Hz): 6.88 (1H, s, CH); 7.14-7.26 (5H, m, H arom); 7.39-7.53
(6H, m, H arom); 7.64 (1H, d, J = 7.79, H arom); 7.81 (1H, d, J = 7.79, H arom); 7.87 (1H, d, J = 8.70, H arom);
7.89 (1H, d, J = 8.70, H arom). 13C NMR spectrum, , ppm: 56.48 (CH); 109.91 (CH); 112.44 (C); 117.62 (CH);
118.76 (CH); 121.67 (CH); 122.66 (CH); 122.96 (CH); 125.48 (CH); 127.76 (CH); 127.91 (CH); 128.92 (CH);
129.05 (CH); 129.22 (CH); 129.57 (C); 131.04 (CH); 131.17 (C); 131.26 (C); 139.10 (C); 140.04 (C); 146.41
(C); 150.54 (C). Mass spectrum, m/z (Irel, %): 348 [M]+ (55), 271 [M-Ph]+ (100), 242 [M-Ph-CHO]+ (12), 227
(5), 213 (11). Found, %: C 82.67; H 4.58; N 8.09. for C24H16N2O. Calculated, %: C 82.74; H, 4.63; N 8.04.
14-(4-Methoxyphenyl)-14H-naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazole (2c) was obtained
in 60% yield (1.38 g) analogously to 2a from 2-methylsulfanylbenzimidazole (1 g, 6.1 mmol), Mannich base 1c
(1.87 g, 6.1 mmol), and potassium carbonate (2.5 g, 18 mmol) in DMF (15 ml) as colorless crystals, mp
136-138°C (ethanol). IR spectrum, , cm-1: 3055 (CH arom), 2932, 2835, 1624 (C=N), 1609, 1539, 1512, 1447,
1285, 1254, 1219, 1177, 1030, 814, 741. 1H NMR spectrum, , ppm (J, Hz): 3.63 (3H, s, CH3); 6.73 (2H, d, J =
8.70, H arom); 6.79 (1H, s, CH); 7.15 (1H, td, J = 7.33, J = 1.37, H arom); 7.20 (1H, td, J = 7.79, J = 1.37, H
arom); 7.33-7.41 (4H, m, H arom); 7.45-7.50 (2H, m, H arom); 7.63 (1H, d, J = 7.79); 7.78 (1H, d, J = 7.79, H
arom); 7.84 (2H, d, J = 8.70, H arom). 13C NMR spectrum, , ppm: 55.26 (CH3); 55.87 (CH); 109.95 (CH);
112.63 (C); 114.49 (CH); 117.59 (CH); 118.75 (CH); 121.55 (CH); 122.73 (CH); 122.85 (CH); 125.40 (CH);
127.67 (CH); 129.01 (CH); 129.13 (CH); 129.57 (C); 130.87 (CH); 131.24 (C); 131.33 (C); 140.23 (C); 146.31
(C); 150.64 (C); 159.67 (C). Mass spectrum, m/z (Irel, %): 378 [M]+ (12), 377 [M-H]+ (11), 271 [M-C6H4OCH3]+
(86), 270 [M-C6H4OCH3]+ (100), 189 (14), 44 (99). Found, %: C 79.30; H 4.83; N 8.14. C25H18N2O2. Calculated, %:
C 79.35; H 4.79; N 7.40.
3-(1-Adamantyl)-14H-naphtho[1',2':5,6][1,3]oxazino[3,2-a]benzimidazole (2d) was obtained
analogously to 2a in 88% yield (2.16 g) from 2-methylsulfanylbenzimidazole (1 g, 6.1 mmol), Mannich base 1d
(2.04 g, 6.1 mmol), and potassium carbonate (2.5 g, 18 mmol) in DMF (15 ml) as yellow crystals, mp 259-
261°C (DMF). IR spectrum, , cm-1: 3066 (CH arom), 2905, 2847 (CH Ad), 1624 (C=N), 1612, 1585, 1535,
1516, 1470, 1285, 1211, 1072, 980, 806, 741. 1H NMR spectrum, , ppm (J, Hz): 1.76-1.84 (6H, m, 3CH2 Ad);
1.92-2.00 (6H, m, 3CH2 Ad); 2.13 (3H, br. s, 3CH Ad); 5.17 (2H, s, CH2); 7.19-7.23 (2H, m, H arom); 7.25-7.31
(2H, m, H arom); 7.57-7.62 (2H, m, H arom); 7.67-7.72 (3H, m, H arom). 13C NMR spectrum, , ppm: 28.96
(3CH Ad); 36.36 (C Ad); 36.82 (3CH2 Ad); 40.48 (CH2); 43.09 (3CH2 Ad); 106.31 (C); 108.59 (CH); 117.32
(CH); 118.57 (CH); 121.28 (CH); 121.61 (CH); 122.98 (CH); 124.03 (CH); 126.03 (CH); 127.90 (C); 130.15
(CH); 130.64 (C); 132.18 (C); 139.84 (C); 145.62 (C); 148.77 (C); 150.47 (C). Mass spectrum, m/z (Irel, %): 406
[M]+ (90), 405 [M-H]+ (100), 349 (24), 311 (30), 271 [M-Ad]+ (62), 216 (54), 202 (52), 44 (92). Found, %:
C 82.77; H 6.40; N 6.93. C28H26N2O. Calculated, %: C 82.73; H 6.45; N 6.89.
This work was carried out in the framework of the Federal Program Priorities for Science and Science
Teaching Personnel for Innovation in Russia 2009-2013 (State Contract P1104, August 26, 2009).
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