Synthesis and Characterization of Spirochromanoid Chalcone Derivatives

 

J.K. Dawale¹*, A.S. Bondge² , P.K.  Tripathi³ and M.M. Krishnan³

¹Research Lab. of Pure and Applied Chemistry, Maharashtra Mahavidhyalaya, Nilanga (MS) INDIA

²Department of Chemistry, Shivneri Mahavidhyalaya, Shirur Anantpal (MS) INDIA

³OCT, Division, National Chemical Lab., Pune (MS) INDIA.

*Corresponding Author E-mail: abhay_bondge@rediffmail.com

ABSTRACT:

The chalcone derivatives of spirochromanoid frame have been synthesized starting from resorcinol. It is converted in to the spirochomanone protected by N-Boc-4-piperidone.the chalcones of this spirochromanone are synthesized by Claisen Schmidt condensation reacting  with 2-chloro benzaldehyde, 2-fluro benzaldehyde, 4-methoxy benzaldehyde, 2,4-dimethoxy benzaldehyde, Benzo-1,3-dioxole-5-carbaldehyde.They are further characterized by their IR, NMR,C¹³, Depth analysis.

 

KEYWORDS: Spirochromanones, Chalcones, N-Boc-4-piperidone.

 

 

INTRODUCTION:

Chalcones (1, 3-diaryl-2-propen-1-ones) are wide spread in natural plant kingdom and belonging to the family “Flavonoids”. These compounds are of wide interest due to their potential applications in various biological activities. Moreover, these chalcones function as an important starting point for the construction of various heterocycles. Structurally Chalcones are open chain flavonoids in which the two aromatic rings are joined by a three carbon, α, β-unsaturated carbonyl system. Fundamentally they can be considered to be derivatives of phenyl styryl ketone.¹

 

Biological activity of Chalcones.

The medicinal use of chalcones dates back to the prehistoric use of chalcone containing herbs such as liquorice (an analgesic) and ashitaba (a diuretic).^2,3 In recent years, these group compounds have been examined for a wide range of biological studies and few of them exhibited potent activities.

 

In the present study, synthesis of some hitherto unknown chalcone derivatives embedded on “privileged” spirochromanone scaffold⁴ has been taken up with a view to apply them for appropriate biological screening.

 

MATERIAL AND METHODS:-

Resorcinol, Acetic acid, N-Boc-4-piperidone, L-proline, 2-chloro, 2-fluro, 4-methoxy, 2, 4-dimethoxy, 3, 4-dioxane benzaldehyde were purchased from Aldrich and used any further purification.

 

Melting points were measured with a BUCHI Melting Point B-540 melting point apparatus and were uncorrected.

¹H NMR spectra were recorded on a BRUKER 200MHz and 400 MHz NMR spectrometers. Chemical shifts were given in parts per million (ppm). Spectra were obtained in CDCl_3.

 

IR spectra were obtained from Perkin-Elmer 68515 PC-FTIR spectrophotometer.

 

Monitoring of reactions was carried out using Merck 60 F₂₅₄ silica gel on aluminum supported TLC plates and visualization with UV light (254 and 365 nm), I₂ and anisaldehyde in ethanol as developing reagents.

 

Scheme 1: Reagents and conditions: (1) ZnCl₂, Ac₂0, 140-50 ⁰C, 70% (2) N-Boc-4-piperidone, L-Proline, DMF, 80 ⁰C

Compound 2 and 3 were separated over flash silica gel column using petroleum ether: ethyl acetate (9:1) as an eluent. Compound 2 and 3 were well characterized by its ¹H NMR, ¹³C NMR and IR spectral studies. The ¹H NMR (200 MHz; CDCl₃) spectrum of compound 3 showed the disappearance of signals due to –COCH₃ (δ 2.64; 6H) and appearance of broad singlet at δ 2.71 (4H) indicating the formation of 4-chromanone skeleton. It was further confirmed by the appearance of typical Spiro carbon resonance at δ 63.0 (quaternary carbon) in ¹³C NMR spectra. On the other hand, the ¹H NMR spectrum of compound 2 also showed the appearance of broad singlet at δ 2.71 which accounts only for 2 protons indicating the formation of spirochromanone skeleton at one side. It was further confirmed by the appearance of signals due to –COCH₃ (δ 2.64; 3H).

 

 

Scheme 2

 

 

Scheme 2

The IR, ¹H NMR, ¹³C NMR,  Depth spectral values, yield and m.p. values are detailed in the table 1, 2, 3, 4 and 5

Compound 2 on treatment with O-Chlorobenzaldehyde in presence of KOH in ethanol at room temperature for 2 days afforded corresponding chalcone 4a in 70% yield. Formation of chalcone 4a was ascertained by its IR spectrum which showed bands at 1638 and 3680 cm^-1 due to chelated   α, β-unsaturated ketone and hydroxyl groups respectively. Moreover, ¹H NMR (CDCl₃; 200 MHZ) spectrum of 4a showed two AB doublets at δ 7.65 and δ 8.36 (J=16 Hz) of α and β  protons of chalcone, respectively. Similarly, other four spirochromanone fused chalcones 4b - 4e were prepared by treating 2 with appropriate aromatic aldehydes.

All of them were characterized thoroughly using IR, ¹H NMR, ¹³C NMR and Depth spectroscopy.

 

Table (1): IR-Spectral data of the spirochromanoid Chalcones.

Sr/ No.	Chalcone forming aldehyde and N-Boc	cm-1 Values
1     2       3           4         5       6     7	2-chloro benzaldehyde     4-methoxy Benzaldehyde     2,4-dimethoxy benzaldehyde           2-fluro benzaldehyde         Benzo1,3-dioxole-5-carbaldehyde       N-Boc Monomer   N-Boc Dimer	669.17,757.29,928.95,1044.76,1263.96,1362.42, 1215.76,1168.67,1315.58,1481.77,1424.65,1570.93, 1638.36,1685.45,2400.49,3019.75,3419.09,3682.92. 669.14,757.74,928.65,1046.73,1171.79,1215.51, 1279.54,1367.20,1423.81,1482.59,1511.89,1605.54, 1560.78,1636.24,1685.48,2400.34,3019.37,3372.99, 3683.03,3790.63. 852.81,862.20,942.11,966.88,974.62,982.71, 997.56,1028.21,1045.35,1107.74,1076.60,1168.89, 1208.32,1244.10,1276.22,1376.84,1556.39,1698.99, 1507.90,1672.70,1460.62,1637.60,1304.87,2727.06, 2854.20,2923.27,3583.29,3508.35,3697.71,3791.91, 3832.91,3832.17,3848.76. 854.41,763.76,748.33,721.33,821.62,979,1051.13, 1153.35,1105.14,1016.42,1321,1365.51,1095.49, 1172.64,1278.72,1377.08,1413.72,1456.16,1573.81, 1687.60,1635.52,1614.32,1687.60,1731.96,2360.71, 2725.23,2852.52,2954.74,3361.69,3498.63. 468,928.55,669.21,875.44,1024.93,1058.13,1427.86 ,1473.87,1116.44,1215.86,1774.08,1521.20,1598.51, 1660.82,2341.91,2400.49,3019.91,3564.22,3617.05, 3686.81,3766.23,3800.64,3820.19,3864. 669.15,771.09,860.68,927.76,973.34,1034.87, 1167.34,1276.72,1243.56,1306.27,1482.51, 1440.80,2399.96,2976.36,3018.33,3443.93. 669.15,771.09,860.68,927.76,973.34,1034.87, 1167.34,1276.72,1243.56,1306.27,1482.51, 1732.80,2399.96,2976.30.

 

Table (2): ¹H-NMR values of spirochromanoid chalcones

Sr No.	Chalcone forming aldehyde and N-Boc	Chemical Shift values in  δ(ppm)
1     2     3     4   5     6   7	2-fluro benzaldehyde     4-methoxy benzaldehyde     2,4-dimethoxy benzaldehyde     2-fluro benzaldehyde   Benzo1,3-dioxole-5-carbaldehyde N-Boc   Monomer   N-Boc Dimer	1.47,1.64,1.70,2.75,3.29,3.17,3.95,3.87,6.55,7.40, 7.45,7.48,7.69,7.82,7.84,7.86,8.32,8.40,8.57, 13.49. 1.47,1.58,1.61,2.00,2.05,2.08,2.74,3.17,3.22, 3.29,3.89,6.53,6.95,7.00,7.26,7.65,7.70,7.89, 7.97,8.58,13.78. 1.21,1.30,1.26,1.47,1.59,1.69,2.05,2.18,2.73, 3.29,3.23,3.17,3.89,3.94,4.14,6.51,6.48,6.59,6.55,7.63 , 7.71, 8.19, 8.26, 8.58, 13.94. 1.47,1.64,2.00,2.06,2.18,2.78,3.17,3.23,3.27, 3.87,3.94,6.54,7.11,7.16,7.21,7.72,7.70,7.73, 7.79,8.04,8.12,8.57,13.52. 1.46,2.64,3.16,3.22,3.28,3.53,3.86,3.94,6.07, 6.48,6.52,6.86,6.90,7.16,7.23,7.45,7.53,7.83, 7.91,8.38,8.56,12.86,13.71. 1.46,2.64,2.72,3.21,3.92,6.49,7.27,8.38,12.86 1.46,1.62,1.97,2.05,2.71,3.26,3.20,3.14,3.86,3.93 6.55,7.27,8.50.

 

Table (3): ¹³C-NMR values of spirochromanoid chalcones

Sr No.	Chalcone forming aldehyde and    N-Boc	Chemical Shift values in δ(ppm)
1       2         3       4       5       6     7	2-fluro benzaldehyde       4-methoxy benzaldehyde         2,4-dimethoxy benzaldehyde       2-fluro benzaldehyde       Benzo-1,3-dioxole-5-carbaldehyde       N-Boc Monomer   N-Boc Dimer	28.34,34.25,47.63,79.21,79.88,105.50,113.71, 115.55,121.77,127.17,128.00,130.32,131.78, 132.53,135.81,141.67,154.56,164.54,170.11, 189.53,192.25. 14.09,23.34,24.62,28.35,29.64,34.24,36.57, 47.66,55.43,76.37,77.00,77.64,79.91,105.39, 113.55,114.49,116.70,127.00,130.85,130.63, 146.04,154.61,162.21,164.27,170.22,189.73, 192.532. 28.37,34.26,47.72,55.55,78.98,79.87,98.36, 105.31,113.50,116.99,105.57,116.58,130.63, 131.36,147.73,154.62,160.76,164.12,163.12, 163.73170.30,189.72,193.06. 28.32,34.24,47.62,77,79.17,79.86,105.43,77, 113.70,115.57,116.09,122.30,124.52,122.53, 129.49,129.54,130.88,132.64,138.43,154.56, 164.48,170.08,189.47,192.57 28.32,34.24,47.62,79.82,105.43,79.17,113.70, 115.57,118.09,122.30,124.52,122.53,129.49, 129.56,130.88,132.64,138.43,154.56,164.48, 170.08,189.47,192.51. 26.44,28.30,34.16,47.56,79.83,79.11,105.19, 113.67,115.31,131.91,154.52,164.41,168.80, 189.54,203.66. 28.35,34.21,39.06,47.73,79.21,79.91,105.60 115.94,127.97,154.62,164.51,189.35.

 

Table (4): Depth values of spirochromanoid chalcones

Sr/ No	Chalcone forming aldehyde	Normal Signal	Negative Signal
1     2     3     4       5	2-chloro benzaldehyde     4-methoxy Benzaldehyde   2,4-dimethoxy benzaldehyde     2-fluro benzaldehyde       Benzo1,3-dioxole-5-carbaldehyde	28.34,105.51,121.77, 127.17,128,130.32, 130.88,131.79,141.68. 23.35,28.35,55.45, 105.39,114.49, 116.70,130.86,146.05. 28.37,55.63,98.37, 105.32,105.57,116.98, 130.64,131.37,141.74. 28.32,105.44,116.53, 121.70,124.59,116.09, 124.52,132.47,129.54, 130.87,132.65,138.49. 28.37,55.63,98.37,105.32, 105.57,116.95,121.70, 124.52,130.64,131.37,132.47, 129.54,141.74.	34.24,47.63     34.25,47.66     34.27,47.37     34.22,47.61       34.22,47.61,36.57

 

Table (5): Yield and m. p. of the synthesised spirochromanoid chalcones

 

 

RESULT AND DISCUSSION:-

The synthesis of spirochromanoid chalcones starting from resorcinol was done in three steps In the first step, synthesis of 4, 6-diacetyl resorcinol (1) is carried out as per reported procedure^{5, 6}

 

Secondly, the mixture of (1) above (5 g; 0.026 mol), N-Boc piperidone (10g; 0.05 mol), L-proline (0.8 g; 30 mol %) in DMF (5 mL) was heated at 100 °C for 10 h. After completion of the reaction (indicated by TLC), the reaction mixture was added in to water, extracted with ethyl acetate (3 X 25 ml). The organic layer was separated, washed with water, brine, dried over anhydrous sodium sulphate and the solvent evaporated under reduced pressure to afford crude compound which was purified over flash silica gel column using Pet ether/EtOAc (9:1) as an eluent to separate compound 2 and 3.

In final step the aldehyde is condensed with the spirochromanone (2) to get the corresponding chalcones.

 

ACKNOWLEDGEMENT:

The author  are grateful to be authorities of National Chemical Lab. Pune for providing the Laboratories and analysis facility and also to be authorities of Dyanand Science College, Latur,Maharashtra Mahavidyalaya Nilanga and Shivneri Mahavidyalaya,Shirur Anantpal for providing facilities to undertake this research project

 

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Received on 05.05.2011        Modified on 21.05.2011

Accepted on 01.06.2011        © AJRC All right reserved