Granthaalayah

NEW APPROACH FOR THE SYNTHESIS OF ARYLOXY 1,3-OXAZINES

 

Ghufran T. Sadeek 1, Mohammad S. Al-jely 2 , Neim H. Saleem 3

1, 3 Chemistry Department, College of Education of Pure Science, Mosul university-Iraq

2 Chemistry Department, College of Education for Girls, Mosul university-Iraq

 

DOI: https://doi.org/10.29121/granthaalayah.v8.i11.2020.2364


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(s1-6)

 

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(S1-6)

Colour

Yield

%

M.P.

(0C)

M.Wt

gm/mol

Molecular

Formula

X = Phenol

Comp.

No.

white

75

64-65

230

C14H14O3

S1

orange

60

50-52

231

C13H13NO3

S2

Brown

56

     Colorless oil

210

C11H14O4

S3

yellow

52

Colorless oil

230

C14H14O3

S4

brown

56

Colorless oil

225

C10H11NO5

S5

brown

60

Colorless oil

225

C10H11NO5

S6

                                                        

4.     SYNTHESIS OF 2-ARYLOXY METHYL -3,1-BENZOXAZINE-4-ONE :(S7-12)

 

       Similar published procedure was used for the synthesis of the above compounds [20]. So, a quimolar amounts of anthranilic acid (0.13g,1mmol) and (s1-6), (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)

Colour

Yield

%

M.P.

(0C)

M.Wt

gm/mol

Molecular

Formula

PHENOLS

Comp.

No.

Brown

 

61

127-128

283

C16H13NO4

S7

yellow

50

68-69

304

C18H12N2O3

S8

brown

66

127

303

C19H13NO3

S9

brown

56

84-86

303

C19H13NO3

S10

purple

61

123-124

298

C15H10N2O5

S11

brown

57

110-111

298

C15H10N2O5

S12

 

 

 

 


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

 

5.     RESULTS AND DISCUSSION

 

5.1. ETHYL SUBISTITUDED ARYLOXY ACETATE(S1-6)

 

These compounds(Scheme1) were synthesized using similar reported procedure102 , and were characterized by the following main absorption bands (ʋmaxcm-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 (s1-6)

others

C-O-C

C=O

C-H aliph.

C-H Ar

X = Phenol

Comp.

No.

……

1050,1144

1678

2952,2867

3198

S1

C=N

1603

1077,1166

1687

2957,2871

3013

S2

……

1056,1154

1628

2954,2849

3100

S3

…..

1048,1150

1655

2953,2835

3064

S4

N-O

Sym 1259

Asym

1410

1103,1158

1672

2971,2837

3003

S5

N-O

Sym

1233

Asym

1387

1084,1105

1638

2922,2849

3064

 

S6

 

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 :(S7-12)

 

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 (ʋmaxcm-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 (s7-12)

IR ν cm-1

X = Phenols compounds

Comp.

No.

C=O

C=C

Ar.

C=N

C-O

 

 

1684

1455,1606

1670

1045,1144

S7

1697

1455,1558

1684

1045,1145

S8

1705

1465,1599

1663

1078,1118

S9

1696

1468,1586

1679

1040,1146

S10

1711

1451,1650

1650

1071,1145

S11

1684

1453,1590

1687

1050,1127

S12

 

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:

 

Como.no.

Structure compounds

1HNMR (PPM)

DMSO-d6

S8

5.18 (s,2H)CH2-O ;(7.04-7.05) (d,2H,C12,C13-H); (7.34-7.53)(t,2H,C17,C18-H) ; (7.60-7.78) (m,2H,C22,C23-H) ;(7.87-7.89) (m,1H,C14-H) ;(8.04-8.05) (m,1H,C11-H) ;8.65 (m,1H,C21 –H)

S10

5.23 (S,2H) CH2-O ;(7.0 -7.02 ) (d,2H,C21,C22-H) ; (7.31-7.53) (m,1H,C23-H) ; (7.64-7.68)(m,3H,C11,C12,C13-H) (7.73-7.69) (m,2H,C17,C18) ; (7.74-7.75) (m, 1H,C19,-H)

  

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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