Abstract: DABCO-CuCl complex, efficiently catalyze the one-pot, three component reaction of an aromatic aldehyde, malonitrile and ‘ or ”-naphthol to yield 2-amino-4H-chromenes in very good yields.
Keywords: DABCO-CuCl complex, 2-Amino-4H-chromenes, One-pot
Introduction
2-amino-4H-chromenes and their derivatives are of considerable interest as they possess a wide range of biological properties,1 such as spasmolytic, diuretic, anticoagulant, anticancer and antianaphylactic activity.2 In addition, they can be used as cognitive enhancers, for the treatment of neurodegenerative diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, AIDS associated dementia and Down’s syndrome as well as for the treatment of schizophrenia and myoclonus.3
The increasing attention during the last decades for environmental protection has led modern academic and industrial groups to develop chemical processes with maximum yield and minimum cost whilst using nontoxic reagents, solvents and catalysts. One of the tools used to combine economic aspects with the environmental ones is the multicomponent reaction (MCR) strategy; this process consist of two or more synthetic steps which are carried out without isolation of any intermediate, thus reducing time, saving money, energy and raw materials.4
As part of our program aimed at developing new selective and environmental friendly methodologies for the preparation of fine chemicals, herein, we report the synthesis of 2-amino-4H-chromenes using DABCO-CuCl complex in good yields.
RESULT AND DISCUSSION
2-Amino-chromenes are generally prepared by refluxing malononitrile, aldehyde and activated phenol in the presence of hazardous organic bases like piperidine for several hours.5 A literature survey revealed that several modified procedures using CTACl,6 TEBA,7 and ‘ alumina8 as catalyst have been recently reported but all these methods require long refluxing hours. Based on previous studies to develop new and heterogeneous catalyst systems for fine chemical preparation, we have studied the three- components synthesis of 2-Amino-4H-chromenes via, one-pot reaction of aldehydes, malonitrile and ‘- or ”-naphthol using DABCO-CuCl complex as available, green and inexpensive catalyst (Scheme1) in good yields.(Table1) .
< Scheme 1>
The scope and the generality of the present method were then further demonstrated by reaction of various aldehydes with malononitrile and ‘-naphtol. In all cases good yields and selectivity were obtained.
It is noteworthy to mention that, the effect of the nature of the substituents on the aromatic ring showed no obvious effect on this conversion, because they were obtained in high yields in relatively short reaction times. The results are shown in Table1.
< Table 1>
A plausible mechanism for this reaction has been suggested in Scheme2. The aldehyde 1 first condenses with malononitrile 2 to afford a-cyanocinnamonitrile derivative 6. The phenol ortho C-alkylation by reaction with the electrophilic C=C double bond giving the intermediate 7. Then the intermediate 7 was cyclized by the nucleophilic attack of OH group on the cyano (CN) moiety and gave the intermediate 8. Finally the expected products 4 were afforded.
< Scheme 2>
Conclusion
In conclusion, DABCO-CuCl complex can serve as an efficient catalyst for the synthesis of 2-amino-4H-chromenes. This procedure offers several advantages including mild reaction conditions, cleaner reaction, high yields of products as well as a simple experimental and work-up procedure which makes it a useful and attractive process for the synthesis of these compounds.
Experimental
All products are known compounds and were characterized by mp, IR, 1HNMR and GC/MS. Melting points were measured by using the capillary tube method with an electro thermal 9200 apparatus. 1HNMR spectra were recorded on a Bruker AQS AVANCE-300 MHz spectrometer using TMS as an internal standard (CDCl3 solution). IR spectra were recorded from KBr disk on the FT-IR Bruker Tensor 27. GC/MS spectra were recorded on an Agilent Technologies 6890 network GC system and an Agilent 5973 network Mass selective detector. Thin layer chromatography (TLC) on commercial aluminum-backed plates of silica gel, 60 F254 was used to monitor the progress of reactions. All products were characterized by spectra and physical data.
Preparation of 2-amino- 2-chromenes: General procedure
A mixture of an appropriate benzaldehyde (1mmol), malononitrile (1mmol), ‘- or ”- naphthol (1mmol) and DABCO-CuCl complex (0.02 g), in methanol (5 mL) were refluxed for appropriate time as indicated in Table 1. After completion of the reaction which was monitored by TLC, the mixture was cooled to room temperature; The precipitate was filtered and washed with ethanol. The crude products were purified by recrystallization from ethanol.
Selected spectal data
Compound 4a:
IR (KBr) (”max, cm’1): 3465, 3318, 3010, 2910, 2200, 1660, 1600, 1550, 1450, 1370, 1267, 1100, 1022, 811, 744; ”H (ppm): 4.90 (s, 1H, H-4), 7.10 (s 2H, NH2), 7.07’7.12 (m, 6H, H-5, 2 ”, 3 ”, 4 ”, 5”), 7.56’7.66 (m, 3H, H-6,8,9), 7.94 (d, 1H, J= 8. 4, H-7), 8.23 (d, 1H, J = 8. 4, H-10); GC/Ms: 298 (M+).
Compound 4e:
IR (KBr) (”max, cm’1): 3450, 3320, 2170, 1660, 1600, 1575,1530, 1500, 1352, 1270, 1190, 1100, 800, 770; ”H (ppm): 5.12 (s, 1H, H-4), 7.29 (s, 2H, NH2), 7.05 (d, 1H, J=8.6, H-5), 7.5’7.7 (m, 3H, H-6,8,9), 7.52 (d, 2H, H- 2 ”, 6 ”), 7.90 (d, 1H, J= 8.4, H-7), 8.15 (d, 2H, H-3 ”, 5 ”), 8.27 (d, 1H, J= 8.6, H-10); GC/Ms: 343 (M+).
References
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Scheme 1. Synthesis of substituted 2-amino-chromenes
Table1. Synthesis of substituted 2-amino-chromenes catalyzed by DABCO-CuCl complex
Entry R Substrate product Time (min) Yield (%)a m.p. (oC)
Observed Reported
1 C6H5 ‘-naphthol 4a 20 90 209 210-2119
2 3-NO2C6H4 ‘-naphthol 4b 15 90 212 212-2149
3 4-MeOC6H4 ‘-naphthol 4c 30 90 191 190-1928
4 4-ClC6H4 ‘-naphthol 4d 15 89 231-232 2328
5 4-NO2C6H4 ‘- naphthol 4e 15 90 242 239-2419
6 4-MeC6H4 ‘-naphthol 4f 30 89 207-209 206-2078
7 3-ClC6H4 ‘-naphthol 4g 15 89 218-220 216-2188
8 2-ClC6H4 ‘-naphthol 4h 25 89 237-238 236-2378
a) Yields refer to isolated products.
Scheme 2. Mechanism for the synthesis of substituted 2-amino-chromenes
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