Article Type: Research Article

 

Article Citation: Ghufran T. Sadeek, Mohammad S. Al-jely, and Neim H. Saleem. (2020). NEW APPROACH FOR THE SYNTHESIS OF ARYLOXY 1,3-OXAZINES. International Journal of Research -GRANTHAALAYAH, 8(11), 137-144. https://doi.org/10.29121/granthaalayah.v8.i11.2020.2364

 

Received Date: 05 November 2020

 

Accepted Date: 30 November 2020

 

Keywords:

New

Approach

Aroyloxy

Oxazines
ABSTRACT

Oxazine compounds have drew the attention  of many researchers to find different approaches to the synthesis of this type of compounds  according to the success of their use in a wide range of pharmaceutical application during the last decades  .It is  also for the difference    reactivity of these analogues is exhaustively depicted and illustrates the rich versatility of this class of starting material. They proved to have most of actions of a combination of other drugs. We are herein investigate the synthesis of ethyl aryloxy acetate(S1-6) from the reaction of the corresponding ethyl bromo acetate with aryl phenols. These intermediates were cyclized with antharanilic acid affording the titled compounds.

1.     INTRODUCTION

 

The chemistry of Oxazine becomes an important branch of heterocyclic compounds not just as synthetic intermediates but also due to the wide spectrum application of this type of compounds in medicine. There are many routes  for their preparation were employed  some of them  from malonyl chloride [1], [2], Ethyl salicylate [3] Other methods of synthesis such as the work of N.R Taati et-al  from  the condensation of 3-amino  propanol with carboxylic acids under solvent free condition [4]. Nadeem Siddiquia and his co-workers have reviewed  the synthesis  of some 1,3- oxazines from the condensation  of  different types of phenols such as hydroquinone, sulfone scaffold, Chavicol, Eugino l, Cardanol as well as ,salicylic acid with different  amines in presence of formaldehyde and studied the biological activity of the synthesized compounds [5].  Ahmed El-Mekabaty in2013 have reviewed versatile methods for oxazine synthesis from antharanilic acid and its derivatives [6]. Sayaji  and Pravina B. Piste  have reported the preparation of  some 1,3- oxazine compounds from phenols and aromatic aldehydes in methanolic ammonia and have studied their anti-microbial activity against two gram positive and two gram negative bacteria .Antifungal activity was screened against Candidaalbicans, Aspergillus niger [7]. Some other researchers have cyclized chalcones into 1,3-oxazines using fly-ash and other catalysts. They also studied their antimicrobial activities. Against gram negative bacteria [8], [9]. Chaitra G. and Rohini RM have also synthesized 1,3-oxazine compounds from pyridyl chalcones and studied their Anti-Oxidant and Anti-Inflammatory activity [10].Among the other medical application of the oxazine compounds is the work of Vashundhra Sharma and his coworkers in synthesis and anti cancer study of  2-oxo-benzo [1], [4] oxazines [11]. J.C. Wouter. de Bruijna and his coworkers have studied the drug designing of 1,4- oxazines and found that their possible multitarget mechanism of the studied compounds as anti-inflammatory drug through quantitative structure-activity relationships (QSAR) [12]. Dadmohammad  and his coworker have reported a green and efficient method for the synthesis of 1,3 oxazine compounds  from aroyl chlorides and hydroxyl naphthaqunone in presence of ammonium thiocyanate at ambient temperature [13], In 1919-2020 researchers studied the synthesis of 1,3-oxazines and  their human DNA topoisomerase I inhibitory potentials [14]. Recently Seyed Gholamhossein Mansouri et-al have synthesized naphtho [1,2-e] [1], [4]oxazines and studied their anticancer and antifungal activity [15]. According to the above utility and applications of this type of heterocyclic compounds and in continuing of our current drug discovery program [16], [17], [18] we have synthesize new 1,3- oxazine derivatives using new route of  condensation protocol.

 

2.     EXPERIMENTAL

 

All melting points were uncorrected using thermal SMP30 UK melting point apparatus .IR spectra were recorded using Alpha (ATR) instrument .¹HNMR spectra were recorded using Varian Agilent 499.53MHZ instrument, DMSO as internal solvent. All chemical were supplied by sigma –Aldrich, BHD and Fluka companies.

 

3.     Synthesis of   ethyl substituted aryloxy acetate(s_1-6)

 

Using  an elsewhere similar procedure of preparation of 1, 3, 4-oxadiazole Derivatives [19], A mixture of any indicated phenols (1mmol), ethyl bromoacetate (0.122g, 1mmol) and anhydrous potassium carbonate (0.55g,4mmol)in 30 ml of  dry acetone was refluxed for 20 h. the reaction mixture was evaporated under reduced pressure, The residue was dissolved in water.The final  solution  was extracted with ether, The ether extract was then  dried over sodium sulphate anhydrous and filtered off .Evaporation of the solvent afforded the crude product which was  crystallized from ethanol .Table(1) below shows the physical properties of the titled compounds.

 

Table 1: the physical properties of compounds(S_1-6)

                                                        

4.     SYNTHESIS OF 2-ARYLOXY METHYL -3,1-BENZOXAZINE-4-ONE :(S_7-12)

 

       Similar published procedure was used for the synthesis of the above compounds [20]. So, a quimolar amounts of anthranilic acid (0.13g,1mmol) and (s_1-6), (1mmol) were heated at (110 ⁰C) on sand bath for 5 hs. The reaction mixture was then treated by addition of 20 ml. ethanol, The crude precipitated product was filtered off and was then crystallized from petroleum ether(60-80) Table(2) below shows the physical properties of the synthesized  compounds.

 

Table 2: Physical properties of compounds(S7-12)

 

 

 

 

Scheme 1: The synthetic pathway for compounds (S1-12)

 

5.     RESULTS AND DISCUSSION

 

5.1. ETHYL SUBISTITUDED ARYLOXY ACETATE(S_1-6)

 

These compounds(Scheme1) were synthesized using similar reported procedure¹⁰² , and were characterized by the following main absorption bands (ʋ_maxcm^-1) at(3003-3198)for C-H aromatic,(2835-2971) for C-H aliphatic,(1628-1687)for C=O,(1048-1166) for C-O-C .The other absorption  bands were shown in Table (3)

 

Table 3: IR spectral data for compounds (s_1-6)

 

¹HNMR for (s₂) compound as a representative of this series of intermediates showed triplet signal at (2.46 ppm) for CH₃ ,q. signal at(3.34 ppm) for CH₂ near Oxygen atom, doublet signal (with and opposite side of ring plane)  resonated at (6.72-6.74 ppm) for CH₂ between carbonyl group and Oxygen atom while quinolone ring protons appeared at ( 7.05 ,7.13,8.22, 8.91 ppm)

 

5.2. 2-ARYLOXY METHYL-3,1-BENZOXAZINE-4-ONE :(S_7-12)

 

These compounds (Scheme1) were synthesized using similar reported procedure as it was mentioned in the experimental part .They are  characterized by the following main absorption bands (ʋ_maxcm^-1) at(1045-1145) for C-O-C , (1452-1650)for C=C aromatic,(1650-1684) for C=N ,(1684-1711) for C=O Table (4) showed the details of  of all compounds spectral data below:

 

Table 4: IR spectral data for compounds (s_7-12)

 

Some selected compounds(S₈andS₁₀) as representative of this series were studied   and revealed the following NMR results. Their proton assignment were referred to the carbon number of the aromatic rings as shown below:

¹HNMR for individual compounds were as follow:

 

  

SOURCES OF FUNDING

 

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

 

CONFLICT OF INTEREST

 

The author have declared that no competing interests exist.

ACKNOWLEDGMENT

 

The authors would like to appreciate the Ministry of higher Education and research for offering Ghufran T. Sadeek a scholarschip and providing the facility to this work which apart of her PhD. Thesis.

 

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