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 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. INTRODUCTIONThe 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. EXPERIMENTALAll
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)
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)
5. RESULTS AND DISCUSSION5.1. 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)
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)
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 FUNDINGThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. CONFLICT OF INTERESTThe author have declared that no competing interests exist. ACKNOWLEDGMENTThe 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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