الفهرس Only 14 pages are availabe for public view
 |  | from | 93 |  |  |
| | | from | 93 | | |
Abstract
Development of preparative simple methods for the synthesis of new analogs of bioactive heterocyclic compounds by using the computer aided molecular designs represents an important task in synthetic organic and medicinal chemistry.
The reaction of -p-bromobenzoylacrylic acid (III) with some nucleophilic reagents such as thiourea gave 2-Amino-4-(p-bromo-benzoylmethyl)-5-hydroxythiazol (LXV). Michael addition reaction of compound (III) with 2-methoxy carbonyl methyl benzoic acid methyl ester (LXVI) compound gave Methyl o-[1,2-dicarboxy-2-(p’-bromo-benzoyl)propyl]benzoate (LXVII) and with 4-Oxo-4,5-dihydrothiazol-2-yl)acetonitrile (LXVIII) give 2-[2’-Amino-5’-oxo-4’,5’-dihydro-4’-(p-bromobenzoylmethyl)-3’-furanyl]-4-oxothiazole (LXIX) and with methyl-N-acetylglycinate (LXX) give 1-Acetylamino-3-(p-bromo-benzoyl)-1,2-dicarboxypropane (LXXI) and finally with thiophenol to give 3-(p-bromobenzoyl)-2-Phenylsulfanylpropionic acid (LXXV).
Reaction of acrylic acid (III) with phosphorous pentachloride afforded 3-(p-bromobenzoyl)prop-2-enoylchloride (LXXII) which reacted with anthranilic acid to give o-[3-(p’-bromobenzoyl)prop-2-enoylamino]benzoic acid (LXXIII), cycliazation by acetic anhydride gave 2-(p-bromobenzoylethenyl)-4H-3,1-benzoxazin-4-one (LXXIV). Scheme (I)
Condensation of 3-(p-bromobenzoyl)-2-Phenylsulfanylpropionic acid (LXXV) with aromatic aldehyde yielded 3-(p-bromobenzoyl)-2-Phenylsulfanyl-4-phenyl-3-butenoic acid (LXXVI) and 3-(p-Bromo-benzoyl)-2-Phenylsulfanyl-4-(3’,4’,5’-trimethylphenyl)-3-butenoic acid (LXXVII). Treatment of compound LXXV with hydrazine hydrate gave 5-(p-Bromophenyl)-3-carboxy-2H-pyrazole (LXXVIII). Scheme (II)
Reaction of 3-(p-bromobenzoyl)-2-Phenylsulfanylpropionic acid (LXXV) with hydroxyl amine hydrochloride through Nucleophilic addition to the carbonyl group yielded 4-(p-bromophenyl)-4-hydroxyimino-2-phenylsulfanylbutanoic acid (LXXIX).
Treatment of LXXV with phosphorous pentachloride afforded 3-(p-bromobenzoyl)-2-phenylsulfanylPropionyl chloride (LXXX) which reacted with anthranilic acid to give o-[3’-(p-bromobenzoyl)-2’-phenylsulfanylpropoylamino]benzoic acid (LXXXI), cycliazation of the latter compound by acetic anhydride gave 2-[2’-(p-bromobenzoyl)-1’-(phenylsulfanyl)ethyl]-4H-3,1-benzoxazin-4-one (LXXXII). Scheme (II)
5-(p-bromophenyl)-3-phenylsulfanyl-3H-furan-2-one (LXXXIII) prepared by reaction of (LXXV) with acetic anhydride which opining by reaction with furfuryl amine giving 3-(p-bromobenzoyl)-N-furan-2-yl-2-phenylsulfanylPropionamide (LXXXIV) or react with hydrazine hydrate to yield 3-(p-bromobenzoyl)-2-Phenylsulfanylpropionic acid hydrazide (LXXXV) which cyclized by acetic anhydride affording 6-(p-bromophenyl)-4-phenylsulfanyl-4,5-dihydro-2H-pyridazin-3-one (LXXXVI). Scheme (II)
Study of molecular modeling by using the computer aided molecular modeling which the Correlation between calculated energies (stabilities) of products, yield percentage and biological activity. The comparison between cyclic structure of this compounds and open compounds according to stability and ant biological activity found that the open structure of the compounds more stable, more binding to the receptors and more biological activity in the same time due to the spread of the charge on the molecules from the both sides. But compounds LXXIV and LXXXII have exception which needs more studies in future to explain the reasons.
Biological activity of the synthesized compounds recommended that compounds LXXV, LXXIV, LXXXII, LXXIII, LXXI, LXXXIII, LXV and LXXIX can be used as good antibacterial active against gram +ve (Streptobacillus sp, Bacillus subtillis and Staphylococcus sp) gram –ve (Neisseriae, Pesudomonas sp. and E.Coli sp) where they have highly active to most of above bacteria and produced with good yield, but it needs more biological studies in the future.
The structures of the synthesized compounds were confirmed by elemental analysis, Infrared, mass and NMR spectroscopy.
Scheme (I)
Scheme (II)
List of compounds
(III) -p-Bromobenzoylacrylic acid
(LXV) 2-Amino-4-(p-bromobenzoylmethyl)-5-hydroxythiazol.
(LXVII) Methyl o-[1,2-dicarboxy-2-(p’-bromobenzoyl)propyl]benzoate.
(LXIX) 2-[2’-Amino-5’-oxo-4’,5’-dihydro-4’-(p-bromobenzoylmethyl)-3’- furanyl]-4-oxothiazole.
(LXXI) 1-Acetylamino-3-(p-bromobenzoyl)-1,2-dicarboxypropane.
(LXXII) 3-(p-Bromobenzoyl)prop-2-enoylchloride.
(LXXIII) o-[3-(p’-bromobenzoyl)prop-2-enoylamino]benzoic acid.
(LXXIV) 2-(p-Bromobenzoylethenyl)-4H-3,1-benzoxazin-4-one.
(LXXV) 3-(p-Bromobenzoyl)-2-Phenylsulfanylpropionic acid.
(LXXVI) 3-(p-Bromobenzoyl)-2-Phenylsulfanyl-4-phenyl-3-butenoic
acid.
(LXXVII) 3-(p-Bromobenzoyl)-2-Phenylsulfanyl-4-(3’,4’,5’-trimethylphenyl)-3-butenoic acid.
(LXXVIII) 5-(p-Bromophenyl)-3-carboxy-2H-pyrazole.
(LXXIX) 4-(p-Bromophenyl)-4-hydroxyimino-2-phenylsulfanyl-butanoic acid.
(LXXX) 3-(p-Bromobenzoyl)-2-phenylsulfanylPropionyl chloride.
(LXXXI) o-[3’-(p’-Bromobenzoyl)-2’-phenylsulfanylpropoylamino]benzoic acid.
(LXXXII) 2-[2’-(p-Bromobenzoyl)-1’-(phenylsulfanyl)ethyl]-4H-3,1-benzoxazin-4-one.
(LXXXIII) 5-(p-Bromophenyl)-3-phenylsulfanyl-3H-furan-2-one.
(LXXXIV) 3-(p-Bromobenzoyl)-N-furan-2-yl-2-phenylsulfanylPropionamide.
(LXXXV) 3-(p-Bromobenzoyl)-2-Phenylsulfanylpropionic acid hydrazide.
(LXXXVI) 6-(p-Bromophenyl)-4-phenylsulfanyl-4,5-dihydro-2H-pyridazin-3-one.