الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
This part deals with synthesis of 6-amino-4-(2-chlorophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 1 via multicomponent cyclocondensation reaction of pyrazolone derivative with malononitrile and o-chlorobenzaldehyde in refluxing ethanol containing a catalytic amount of piperidine (Scheme I). The behavior of enaminonitrile 1 towards different carbon electrophiles was investigated. Thus, heating enaminonitrile 1 with formic acid for eleven hours yielded the unexpected product which identified as 3-(2-chlorophenyl)-3-(5-hydroxy-3-methyl-1H-pyrazol-4-yl)propanoic acid 2. On the other hand, condensation of enaminonitrile derivative 1 with triethyl orthoformate gave the corresponding iminoether 3.
The behavior of iminoether 3 towards a group of nitrogen nucleophiles was investigated. Thus, aminolysis of the iminoether 3 with 4-amino-2,3-dimethyl-1-phenyl-1,2-dihydropyrazol-5-one and cyclohexyl amine in refluxing ethanol or o-aminophenol in dioxane gave the corresponding iminopyrimidine derivatives 4, 5 and 6, respectively (Scheme II). However, heating iminoether 3 with o-phenylenediamine and/or ethylenediamine yielded the β-enaminonitrile derivative 1. Furthermore, conducting iminoether 3 with thiosemicarbazide in dioxan afforded triazolo[1,5-c]pyrimidin-2-amine derivative 7.
Part II- Utility of Enaminonitrile Functionality in Synthesis of Novel Annulated Benzochromenes
This part deals with synthesis of 2-amino-4-(2-chlorophenyl)-4H-benzo[h]chromene-3-carbonitrile 8 and 2-amino-4-(4-chlorophenyl)-4H-benzo[h]chromene-3-carbonitrile 9 via multi-components reaction of malononitrile, α-naphthol, 2-chlorobenzaldehyde and/or 4-chlorobenzaldehyde in ethanol containing a catalytic amount of piperidine (Scheme III). The behavior of understudy enaminonitrile 8 towards different electrophilic and nucleophilic reagents was evaluated. Thus, refluxing of enaminonitrile 8 with acetic anhydride afforded benzo[7,8]chromeno[2,3-d]pyrimidin-8-one 10. On the other hand, refluxing 8 with acetyl chloride yielded benzo[7,8]chromeno[2,3-d][1,3]oxazin-8-one derivative 11. Furthermore, boiling of 8 with triethyl orthoformate afforded the corresponding iminoether 12.
Iminoether 12 was utilized for synthesis of annulated benzochromene via reaction with various nitrogen nucleophiles. Thus, stirring iminoether 12 with excess hydrazine hydrate afforded benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine derivative 13, while its reaction with thiosemicarbazide in dioxane yielded 1-{[4-(2-chlorophenyl)-3-cyano-4H-benzo[h]chromen-2-ylimino]-methyl}thiosemicarbazide 14 )Scheme IV(. Furthermore, treatment of iminoether 12 with p-toluene sulphonohydrazide in refluxing dioxane yielded benzo[7,8]chromeno[2,3-d]pyrimidine derivative 15. benzo[h]chromene benzohydrazide derivative 16 was obtained upon conducting iminoether 12 with 2-hydroxybenzohydrazide in boiling dioxane. However, aminolysis of iminoether 12 with either 2-furanylmethanamine and/or 2-aminopyridine in refluxing dioxane yielded formamidine derivatives 17 and 18, respectively.
Iminoether 12 was utilized for synthesis of annulated benzochromene via reaction with various nitrogen nucleophiles. Thus, stirring iminoether 12 with excess hydrazine hydrate afforded benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine derivative 13, while its reaction with thiosemicarbazide in dioxane yielded 1-{[4-(2-chlorophenyl)-3-cyano-4H-benzo[h]chromen-2-ylimino]-methyl)}thiosemicarbazide 14 Scheme IV. Furthermore, treatment of iminoether 12 with p-toluene sulphonohydrazide in refluxing dioxane yielded benzo[7,8]chromeno[2,3-d]pyrimidine derivative 15. Upon conducting iminoether 12 with 2-hydroxybenzohydrazide in boiling dioxane yielded benzo[h]chromene benzohydrazide derivative 16. However, aminolysis of iminoether 12 with either 2-furanylmethanamine or 2-aminopyridine in refluxing dioxane yielded formamidine derivatives 17 and 18, respectively.
Additionally, conducting of the iminoether derivative 12 with 2-cyanoacetic acid hydrazide in dioxane gave fused triazolopyrimidine drivative 19. However, condensation of compound 19 with p-methoxyenzaldehyde and/or salicylaldehyde in refluxing dioxane in the presence of a catalytic amount of piperidine afforded arylidene 20 and chromenone derivatives 21, respectively. On the other hand, hydrazonyl derivative 22 was separated upon treatment of 19 with 2-hydroxy-benzenediazonium chloride in presence of sodium acetate at -5oC yielded hydrazonyl derivative 22 (Scheme V).
Furthermore, the behavior of understudy enaminonitrile 9 towards different electrophilic reagents was investigated. Thus, benzo[7,8]chromeno[2,3-d]pyrimidinone 23 a sole product was yielded when enaminonitrile 9 was subjected to chloroacetyl chloride in refluxing dioxan for 6 hours (Scheme VI). On the other hand, refluxing enaminonitrile 9 with triethyl orthoformate gave ethyl formimidate derivative 24 which was used as key intermediate for synthesis of annulated benzo[7,8]chromene derivative via reaction with nitrogen nucleophiles. Thus, treatment of ethyl formimidate 24 with p-toluene sulphonohydrazide in refluxing dioxane yielded benzo[7,8]chromeno[2,3-d]pyrimidine derivative 25, while refluxing of ethyl formimidate 24 with benzoylhydrazide in dioxane afforded chromenotriazolopyrimidine derivative 26.
Larvicidal efficiency of novel annulated pyrazolopyranopyrimidine derivatives; structurally related to neonicotinoids, was investigated and assessed their toxicity effects in comparison with nitenpyram; as reference stander, against the lab and field strains of 3rd instar larvae of C. pipiens and 2nd instar larvae of Musca domestica. Nitenpyram exhibited approximate toxicity to both C. pipiens and M. domestica larvae with LC50 values 1.81 and 1.74 ppm, respectively for lab strain, and 2.74 and 2.05 ppm, respectively for field strain while, the iminoether 3 was highly toxic to both lab and field strains with LC50 values 3.01 and 6.12 ppm for C. pipiens larvae, respectively, 2.23 and 2.32 ppm for M. domestica relative to other tested compounds. Over all , the toxicities were arranged as following: 3 > 1 > 4 > 2 > 5 for lab strain of C. pipiens while, 3 > 1 > 2 > 4 > 5 for lab strain of M. domestica.