Electron Impact Ionization Mass Spectra of 3-Amino 6-Chloro- 2-methyl Quinazolin-4-(3H)-one Derivative

Looking at the previous studies on quinazolinones derivatives, only limited information’s are available on their mass spectral along with the preparation of novel quinazolin-4-(3H)-one derivatives The condensation of Methyl-2-amino-4-Chlorobenzoate with acetic anhydride yielded the cyclic compound 2-methyl 7-Chloro-1, 3-benzo-oxazine-4-one (1) which further produce 3-Amino-2-Methyl 7-Chloro quinazolin-4(3H)-ones (2) via the reaction with hydrazine hydrate. The compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance (1H and 13C), Gas Chromatography-Mass spectrophotometry and Elemental analysis. Discussion: The molecular ion of m/z 235 fragments to give m/z 220 by loss of –NH group. The ion of m/z 220 was broken to give m/z 206 by losing CH2 group and fragment to m/z 177 by loss of HCO. This fragmented to m/z 162 by loss of –CH3 group and then m/z 136 by loss of CN group. The loss of O gave m/z 120 which fragment to give m/z 93 by loss of –HCN and finally gave m/z 65 by loss of CO group. Conclusion: The electron impact ionization mass spectra of compound 2show a weak molecular ion peak and a base peak of m/z 235resulting from a cleavage fragmentation. Compound 2 give a characteristic fragmentation pattern. From the study of the mass spectra of compound 2, it was found that the molecular ion had fragmented to the m/z 220. The final fragmentation led to ion of m/z 93 and ion of mass m/z 65, respectively.


Introduction
An introduction to Medicinal Chemistry gives us a very detailed look at the world of medicine [1]. Principles of Medicinal chemistry is necessary to consider physiochemical properties, used to develop new pharmacologically active constituents and their mechanism of action and many of them are entered to pharmacological screening for determining their biological activity. This random screening process has been inefficient, but it has resulted in identification of new lead compounds whose structures have been optimized to produce clinical agents [2]. A rich tradition of analog design strategies has evolved for creating new compounds within medicinal chemistry research for biological evaluation [3].
Heterocyclic chemistry is a chemistry involving the heterocyclic compounds, which has atoms of at least two different elements as number of ring. The heterocyclic atoms may be inorganic, though the compound contains carbon atoms in the ring. The word hetero means " different from carbon and hydrogen" Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide. In particular, heterocyclic structures form the basis of many pharmaceutical, agrochemical and veterinary products [4]. Heterocyclic chemistry is a potential part of the synthetic organic chemistry, covering a wide variety of bioactive molecules. Among six-membered heterocycles, quinazoline occupies significant position and is commonly found in a wide variety of natural products, synthetic pharmaceutical molecules, and other functional materials [5].
The critical role played by heterocycles in drug design cannot be denied. Even where the natural substrate or ligand for a biological target does not contain a heterocycle, drugs whether of natural or man-made origin that act on that target frequently contain heterocyclic groups [6]. Quinazolinone is one of the most important heterocyclic compound, weak base, having varied biological activities and still of great scientific interest now a days. They are widely found in bioorganic and medicinal chemistry with application in drug discovery. Literature studies on quinazolinones have shown that these derivatives possess a wide variety of biological activities such as antioxidant, antifungal, antibacterial, anticonvulsant, antiinflammatory, antihyperlipidemic, anticancer, antimalarial, antispasmodial analgesic, antiviral, antitubercular and antimicrobial activities [7][8][9][10][11][12][13][14][15][16][17][18][19].

Materials and Methods General Experimental Procedure
All reagents and solvents were products of sigma-Aldrich, Germany. Melting points were determined on a kofler hot stage apparatus and were uncorrected. IR spectra were recorded on a Buck scientific IR M500 instrument. The 1 H-and 13 C-NMR spectra were recorded in DMSO-d6 at 400 MHz with HAZ VOLATILE V2. M spectrophotometer. Chemical shifts were reported in ppm relative to tetramethylsilane. Gas chromatography-Mass spectra were obtained on a Finingan MAT 44S mass spectrometer operating at 70eV. Elemental analysis agreed favourably with the calculated values Analytical thin layer chromatography (TLC) was used to monitor the reactions.

Experimental
Reagents and solvents were purchased from sigma-Aldrich chemical supplier in Germany. Melting points were determined on a Kofler hot stage apparatus and are uncorrected. IR spectra were recorded on a Buck scientific IR M500 instrument. The 1 H and 13 C NMR spectra were recorded in DMSO at 400MHz with HAZ VOLATILE V2.M. Chemical shifts are reported in ppm relative to tetramethylsilane. Gas chromatography Mass spectra were obtained on a HAZ VOLATILE V2.M (400MHz) and chemical shifts are reported in ppm relative to tetramethylsilane as reference standard. Elemental analysis agreed favourably with the calculated values. Analytical thin layer Chromatography (TLC) was used to monitor the reactions.

Chemistry
The introduction of 2-Amino substituent is a successful strategy to improve the chemical stability of benzoxazinone. Due to the pharmacological activities of 4(3H)-quinazolinone derivatives, 2,3-disubstituted derivatives of quinazoline-4-one was synthesized via the interaction of the benzoxazinone derivative with nitrogen nucleophile with the aim of obtaining more pricise information about the course of the reaction and some interesting pharmaceutical compounds. The reaction of 4, 5-disubstituted derivatives of methylanthranilate and acetic anhydride yielded the cyclic compound 2-methyl-6, 7-dimethoxyl-benzo-1, 3-oxazin-4one. The reaction of this compound with hydrazine hydrate yielded the novel 2, 3-disubstituted quinazoline-4-one.
Structural elucidations of compounds synthesized were characterized by correct elemental analysis and careful inspections of spectral data. Looking at the 1 H NMR spectra of the compounds synthesized, compound 1 displayed a singlet signal at: δ 3.78 attributed to methoxy group and singlet at δ 3.68 which was due to methyl group. Other singlets appeared at δ7.16 and 6.40 attributed to aromatic protons. Also, 1 H NMR spectrum of compound 2 showed a characteristic signal at δ 2.56 (singlet) corresponding to methyl group and duplet at: δ 3.90 for methoxy group. Two singlets appeared at δ7.41 and 7.10 attributed to aromatic protons. Another signal appeared at 5.80 which was attributed to the protons of the amino group. For the IR spectra, compound 1 was characterized by absence of υ NH 2 and presence of υ C-O stretch in 1101cm -1 region of the compound. Compound 2 was characterized by absence of υ C-0 and presence of υNH 2 in 3301cm -1 region of the compound.  Table 2). Table 4 lists the m/z (relative abundance, %) values of principal fragments of the studied compound, while figure 1 illustrates the mass spectrum of the compound. The mass spectrum of the compound shows a molecular ion of m/z 210 corresponding to the molecular mass of the compound. The molecular ion of m/z 210 fragment to give m/z 195 by loss of -NH group. The ion of m/z 195 was broken to give m/z 181 by losing CH 2 group and fragment to m/z 146 by loss of Cl. This fragmented to m/z 120 by loss of -HCN group which fragment to give m/z 93 by loss of -HCN and finally gave m/z 65 by loss of CO group.

Conclusion
The present work shows that the mass spectra of compound 2 has relatively small molecular ion and peaks typical of a cleavage and rearrangement processes type fragmentation. Compound 2 give a characteristic fragmentation pattern with a very stable fragment of benzopyrazolone (m/z210).