Two-step novel synthesis of 2-amino-6-(1,3-dioxo-2,3-dihydro-1H-inden-2-yl) -4,7-diphenyloxepine-3-carbonitrile and 5-(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)- 2-imino-6-phenyl-2H-pyran-3-carbonitrile

Article abstract of DOI:10.1080/00397910600639711

Starting from indan-1,3-dione, a novel two-step synthesis of the oxepine derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction conditions is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600639711

This article was downloaded by: [University of Kent]
On: 26 November 2014, At: 12:44
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Two‐Step Novel Synthesis of
2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)
and
5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐
Tarek M. Abou Elmaaty a
a Idaho State University, Department of Chemistry , Pocatello, Idaho, USA
Published online: 22 Sep 2006.
To cite this article: Tarek M. Abou Elmaaty (2006) Two‐Step Novel Synthesis of
2‐Amino‐6‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐4,7‐diphenyloxepine‐3‐carbonitrile and
5‐(1,3‐Dioxo‐2,3‐dihydro‐1H‐inden‐2‐yl)‐2‐imino‐6‐phenyl‐2H‐pyran‐3‐carbonitrile, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:16, 2281-2285, DOI:
10.1080/00397910600639711
To link to this article: http://dx.doi.org/10.1080/00397910600639711
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 36: 2281–2285, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600639711
Two-Step Novel Synthesis of 2-Amino-6-
(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4,7-
diphenyloxepine-3-carbonitrile and
5-(1,3-Dioxo-2,3-dihydro-1H-inden-2-yl)-2-
imino-6-phenyl-2H-pyran-3-carbonitrile
Tarek M. Abou Elmaaty
Idaho State University, Department of Chemistry, Pocatello, Idaho, USA
Abstract: Starting from indan-1,3-dione, a novel two-step synthesis of the oxepine
derivatives 5a,b and the pyran derivatives 7 and 8 under very simple reaction
conditions is described.
Keywords: oxepin derivatives, pyran derivatives, indan-1,3-dione chemistry
INTRODUCTION
Oxepine derivatives (Klaivanolide from the plant Uvaria klaineava) are known
as potent antileishmanial agents[1] and as antiallergic drugs.[2] Because activity
in this particular area has not been especially high, we report herein the synthesis
of new derivatives of the oxepine molecule as well as a new pyran heterocycle,
both linked to an indandione moiety that is expected to increase their biological
activity.[3–5] This motivation is in addition to our interest in the synthesis of
functionally substituted heterocycles utilizing enaminones[3–7] as precursors
for the targeted compounds. The synthesis of these classes of compounds
allows for good yield and is simple and facile. Also, it represents a novel
one-step synthesis of the seven-membered oxepine ring from 1,3-diketone.
Received in the USA January 26, 2006
Address correspondence to Tarek M. Abou Elmaaty, Idaho State University,
Department of Chemistry, Campus Box 8023, Pocatello, ID 83209, USA. E-mail:
tasaid@hotmail.com
2281

2282
T. M. A. Elmaaty
RESULTS AND DISCUSSION
Treatment of 2-phenacylindan-1,3-dione (1)[8] with dimethyl formamide
dimethylacetal in dry xylene under reflux afforded the unkown enaminone
derivative 2 in (80%) yield. Structure of compound 2 was confirmed by its
spectral and elemental analysis.
Compound 2 was treated with arylidenemalononitriles (3a,b) in ethanol
containing a catalytic amount of piperidine (0.5 mL) to give the oxepine
derivatives 5a,b. Compound 5 is believed to be formed via the Michael-
type addition of the enaminone 2 to the activated double bond in 3,
followed by dimethylamine elimination and cyclization to give the oxepine 5.
On the other hand, when 2 was treated with malononitrile under the same
reaction conditions, the iminopyran derivative 7 was obtained. Compound 7
underwent hydrolysis in aqueous hydrochloric acid to give the pyranone
derivative 8 in good yield.
Elemental analyses of the synthesized compounds were found to be in
accordance with the proposed structures.
CONCLUSION
In conclusion, this article reports a novel, simple method for the synthesis of
six- and seven-membered heterocycles, which may contribute to the
chemistry of heterocyclic compounds as well as their expected biological
activity.
EXPERIMENTAL
All melting points were obtained in open capillary tubes and are uncorrected.
The IR spectra were recorded in KBr discs using a Perkin Elmer FT spectropho-
tometer model Spectrum RX1. The 1H and 13C NMR spectra were determined
on a Varian Mercury 300-MHz FT-NMR 300 with DMSO-d6 as solvent, with
chemical shifts reported in parts per million (ppm) (d) relative to TMS as
internal standard. Mass spectra were measured on a GC/MS INCOS XL
Finnigan MAT. Microanalysis was performed in house using a Perkin Elmer
Series II CHNS/O Analyzer 2400. Reagents were purchased from Aldrich.
2-(3-Dimethylamino)-1-oxo-1-phenylprop-2-en-2-yl)-2H-inden-1,
3-dione (2)
A mixture of compound 1 (10 mmol) and DMFDMA (10 mmol) in xylene
(30 mL) was heated under reflux for 4 h (Scheme 1). The reaction mixture
was then evaporated under vacuum. The remaining residue was triturated

Two-Step Novel Synthesis of Oxepine Derivatives
2283
Scheme 1.
with ethanol to give a solid product that was collected by filtration and crystal-
lized from ethanol to give compound 2 as red crystals.
Yield 70%, mp 2408C. IR: 1729, 1705 (3 CO). 1H NMR (DMSO-d6): 2.65
(s, 6H, 2N-CH3), 5.18 (s, 1H, CH), 6.53 (s, 1H, CH), 7.45–7.97 (m, 9H, arom-
H). 13C NMR (DMSO-d6): 200.5, 193.5 (3 CO), 149.1 (vinyl carbons), 63.1,
43.5 (aliphatic carbons). MS: m/z 319.00 (Mþ) (100 %). Anal. calcd. for
C20H17NO3 (319.35): C, 75.22; H, 5.37; N, 4.39. Found: C, 75.43; H, 5.12;
N, 4.51%.

2284
T. M. A. Elmaaty
General Method for the Preparation of Compounds 5a,b and 7
The appropriate arylidene malononitrile or malononitrile (10 mmol) was
added to a solution of compound 2 (10 mmol) in ethanol (30 mL) containing
piperidine (0.5 mL). The reaction mixture was then heated under reflux for
6 h. The reaction mixture was left to cool, and the deposited solid was
collected by filtration to give compounds 5a,b and 7.
2-Amino-6-(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4,
7-diphenyloxepine-3-carbonitrile (5a)
Compound 5a was obtained as brown crystals from ethanol, yield 75%, mp
1
2548C. IR: 3345, 3330 (NH2), 2220 (CN), 1729 (CO). H NMR (DMSO-
d6): 4.0 (br, 2H, NH2), 5.19 (s, 1H, CH), 6.8 (s, 1H, 4H-oxepine), 7.43–8.1
(m, 14H, arom-H). 13C NMR (DMSO-d6): 193.0 (CO), 177.0, 147.0, 142.0,
130.9, 105.5, 60.5 (vinyl carbons), 141.2, 133.0, 132.5, 129.5, 129.1, 128.5,
128.1, 126.2 (aromatic protons), 115.2 (CN), 60.9 (CH). MS: m/z 430.00
(Mþ) (100%). Anal. calcd. for C28H18N2O3 (430.45): C, 78.13; H, 4.21; N,
6.51. Found: C, 77.99; H, 4.33; N, 6.34%.
2-Amino-2-benzyl-6-(1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4-
(thiophene-2-yl)oxepine-3-carbonitrile (5b)
Compound 5b was obtained as red crystals from ethanol, yield 73%, mp
1
2008C. IR: 3450, 3330 (NH2), 2220 (CN), 1729 (CO). H NMR (DMSO-
d6): 4.0 (br, 2H, NH2), 5.19 (s, 1H, CH), 6.8 (s, 1H, 4H-oxepine), 7.0–
8.1 (m, 12H, arom-H and thiophene-H). 13C NMR (DMSO-d6): 196.00
(CO), 141.00, 137.3, 133.3, 128.5 (aromatic carbons), 136.3, 130.3,
128.00, 127.00 (thiophene carbons), 175.00, 143.00, 142.00, 137.00,
108.00, 61.00 (vinyl carbons), 115.5 (CN), 37.00 (CH). Anal. calcd. for
C26H16N2O3 S (436.48): C, 71.54; H, 3.69; N, 6.42. Found: C, 71.59; H,
3.50; N, 6.40%.
5-(1,3-Dioxo-2,3-dihydro-1H-inden-2yl)-2-imino-6-phenyl-2H-
pyran-3-carbonitrile (7)
Compound 7 was obtained as yellow crystals from ethanl/DMF, yield
1
75%, mp 2738C. IR: 3400 (NH), 2220 (CN), 1729 (CO). H NMR (DMSO-
d6): 5.6 (s, 1H, 4H-pyran), 5.9 (s, 1H, CH), 7.45–8.5 (m, 9H, arom-H),
8.83 (s, 1H, NH). MS: m/z 340 (Mþ) (100%). Anal. calcd. for
C21H12N2O3 (340.33): C, 74.11; H, 3.55; N, 8.23. Found: C, 74.40; H, 3.33;
N, 8.20%.

Two-Step Novel Synthesis of Oxepine Derivatives
2285
5-(1,3-Dioxo-2,3-dihydro-1H-inden-2yl)-2-oxo-6-phenyl-2H-pyran-
3-carbonitrile (8)
A solution of compound 7 (10 mmol) in hydrochloric acid (10 mL) was
refluxed for 5 min. The solution was made alkaline with aqueous 20%
sodium hydroxide solution. Compound 8, which precipitated, was collected
by filtration and crystallized from methanol, yield 70%, mp 2208C. IR:
1
3450, 3330 (NH2), 2220 (CN), 1729, 1700 (2 CO). H NMR (DMSO-d6):
5.19 (s, 1H, CH), 5.9 (s, 1H, 4H-pyran), 7.45–8.5 (m, 9H, arom-H). 13C
NMR (DMSO-d6): 194.5 (2 CO), 150 (CO-O), 165.0, 135.1, 107.3, 104.2
(vinyl carbons), 141.4, 133.2, 130.5, 128.00, 126.5 (arom carbons), 115.3
(CN), 59.5 (CH). MS: m/z 341(Mþ) (100%). Anal. calcd. for C21H11NO4
(341.32): C, 73.90; H, 3.25; N, 4.10. Found: C, 73.89; H, 3.20; N, 4.31%.
REFERENCES
1. Akendengue, B.; Roblot, F.; Loiseau, P. M.; Bories, C.; Ngou-Milama, E.;
Laurens, A.; Hocquemiller, R. Phytochemistry 2002, 59, 885.
2. Ohmori, K.; Hyashi, K. I.; Kaise, T.; Ohshima, E.; Kobayashi, S.; Yamazaki, T.;
Mukouyama, A. Jpn J. Pharmacol. 2002, 88, 379.
3. Elmaati, T. A.; Said, S. B.; Elenein, N. A.; Sofan, M. A.; Khodeir, M. Polish J.
Chem. 2002, 76, 945.
4. Elmaati, T. A.; El-Taweel, F. M. A. J. Chin. Chem. Soc. 2002, 49, 1045.
5. Elmaati, T. A. Acta Chem. Slov. 2002, 49, 721.
6. Elmaati, T. A. J. Heterocycl. Chem. 2004, 41, 947.
7. Padmanabhan, P. V.; Ramna, D. V.; Ramadas, S. R. Indian J. Chem. 1983, 27, 4502.
8. Schaeffer, H. J.; Vince, R. J. Org. Chem. 1962, 27, 4502.