Methodology Study and a Practical, Cost Efficient Synthesis of a 3-(2-Methyl-1-oxo-indan-2-ylmethyl)-isochromen-1-one

 

S. Shiva Rama Krishna*1 and R. Sreenivasulu2

*1Research Scholar, Mewar University, Rajasthan, India

2Research Supervisor, Mewar University, Rajasthan, India

*CorrespondingAuthorE-mail:shivarama_samala@rediffmail.com

 

ABSTRACT:

1-Oxo-1H-isochromene-3-carbaldehyde (1) reacts with Indan-1-one (2) to offer 4-(1-Oxo-indan-2-ylidenemethyl)-isochromen-1-one (3) which on reaction with liquid ammonia produces 3-(1-Oxo-indan-2-ylmethyl)-isochromen-1-one (4). Compound 4 is reduced with LDA to 3-(2-Methyl-1-oxo-indan-2-ylmethyl)-isochromen-1-one (5). The structures of the compounds are confirmed by spectral data.

 

KEYWORDS:Coumarins, anticoagulant, anti-inflammatory.

 

 


INTRODUCTION:

Coumarins have been established as a well known naturally occurring heterocyclic compounds isolated from various plants. Coumarins comprise a very large class of compounds found throughout the plant kingdom. They are found at high levels in some essential oils, particularly cinnamon bark oil (7,000 ppm), cassia leaf oil (up to 87,300 ppm) and lavender oil. Coumarin is also found in fruits (e.g. bilberry, cloudberry), green tea and other foods such as chicory. Most of the coumarins occur in higher plants, with the richest sources being Rutaceaeand Umbelliferone[1]. They belong to the family of lactones having 1-benzopyran-2-one system that can be isolated from plants as well as can be carried out in the laboratory[2]. Coumarin is versatile pharmacophore which exhibits a wide variety of biological activities like antibacterial[3] and antimicrobial[4]. Coumarins occupy a special role in nature.

 

They belongs to the flavonoid class of plant secondary metabolite, which exhibit a variety of biological activities, associated with low toxicity and have achieved considerable interest due to their beneficial potential effects on human health[5]. Coumarin derivatives have been reported for anticoagulant, anti-inflammatory [6], antimicrobial[7], antiHIV, antioxidant[8], antiallergic, anticancer[9] and anti proliferative and antiviral[10] activities. Isoxazole derivatives have analgesic[11], anti inflammatory, antimicrobial, anti tumour, antiHIV, herbicidal, fungicidal and CNS stimulant[12] activities.

 

The wide variety of heterocycles can be synthesized due to the presence of three electrophilic centres in the molecule of 1 and its ability to open or retain pyran-4-one ring.[12] Many of chromene derivatives exhibit significant biological activity, such as antitumour,[13,14] antimycobacterial [15] or antiviral. [16]

 

EXPERIMENTAL SECTION:

Chemicals and solvents were reagent grade and used without further purification.   The 1H NMR was recorded in the indicated solvent on a Varian 400 MHz spectrometer with TMS as internal standard. All chemical shifts (δ) were reported in ppm from internal TMS. Mass spectra were measured on a Jeol JMS D-300 spectrometer. The homogeneity of the compounds was checked using pre-coated TLC plates (E.MerkKieselgel 60 F254).


Scheme

 

3-(1-Oxo-indan-2-ylidenemethyl)-isochromen-1-one (3)

 

 

 


In a clean and dry RBF both starting materials taken in ethanol added aqueous NaOH (2.0Eq) and continue the reaction at RT about 12hr and monitor the reaction by TLC, reaction mixture poured in ice and cold water extracted with DCM dried and concentrated

 

1HNMR(DMSD-d6, 400 MHZ ):=7.72(S.S1H),7.23(d,1H,J=3.2HZ), 6.83-6.98(m,4H), 6.79(d, 1H,J=3.2 HZ), 6.65(d, 2H,J=7.8 HZ),6.38(S,1H), 6.44(S,2H). MS: m/z, 289 (M+1).


3-(1-Oxo-indan-2-ylmethyl)-isochromen-1-one (4)

 

 


Brief process: 

In dry and clean round bottom flask under nitrogen atmosphere charged starting material, ethanol solvent and followed Lithium metal content mineral oil then reaction mass chilled to 0°C passed slowly liquid ammonia and the completion of the reaction monitored by TLC, reaction mixture poured in ice and cooled water neutralized with dil HCl and extracted with toluene and dried over Na2SO4 concentrated and dried.

1HNMR(DMSO-d6, 400 MHZ ):=6.48(D,2H,J=7.8HZ),7.21(d,1H),7.08(d, 2H,J=7.8 HZ), 6.81(m,2H), 6.67(d, 1H), 6.18(S,1H), 3.48(M,1H)), 2.83(M,2H)2.23(M,2H).

 

13CNMR(DMSO-d6, 100 MHZ ): =192.01, 158.02, 142.1, 140.2, 136.1, 134.2, 132.4, 128.3, 128.0, 126.8, 126.2, 125.8, 120.4, 108.1, 52.1, 48.6, 44.0, 21.6. MS: m/z, 291.2 (M+1).


 

 

 

 

3-(2-Methyl-1-oxo-indan-2-ylmethyl)-isochromen-1-one (5)

 


 

In a clean and dry RBF starting material charged in dimethoxyethane (DME) solvent and under nitrogen atmosphere slowly LDA is added at 0-5°C and after 30min methyl iodide is added drop wise at 0-5°C and continue the reaction at 25°C about 2hr, completion of the reaction monitored by TLC, reaction mixture poured in ice and cold water neutralized with dil hydrochloric acid extracted with ethyl acetate dried over Na2SO4 and concentrated

 

1HNMR(DMSO-d6, 400 MHZ ):=7.82(d,2H,J=7.8HZ),7.61(d,2H,J=7.8HZ),7.53(M,2H), 7.32(m,2H), 6.31(S, 1H),6.31(S,1H), 2.30(m,2H) ), 2.00(m,2H),1.49(s,3H); MS: m/z, 305 (M+1).

 

REFERENCES:

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16.     Kirkiacharian, S.; Thuy, D. T.; Sicsic, S.; Bakhchinian, R.; Kurkjian, R.; Tonnaire, T. Farmaco2002, 57, 703.

 

 

 

 

 

Received on 07.02.2018         Modified on 03.03.2018

Accepted on 13.04.2018         © AJRC All right reserved

Asian J. Research Chem. 2018; 11(3):585-587.

DOI:10.5958/0974-4150.2018.00104.9