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العنوان
BEHAVIOR OF SOME PHTHALAZINONE
DERIVATIVES TOWARD SOME CARBON ELECTROPHILES:
المؤلف
Kadhim, Mohammed Abed.
هيئة الاعداد
باحث / Mohammed Abed Kadhim
مشرف / Maher Abdel Aziz El-Hashash
مشرف / Dalal Besanty Guirguis
مناقش / Dalal Besanty Guirguis
تاريخ النشر
2015.
عدد الصفحات
211 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Organic Chemistry
تاريخ الإجازة
1/1/2015
مكان الإجازة
جامعة عين شمس - كلية العلوم - قسم الكيمياء
الفهرس
Only 14 pages are availabe for public view

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Abstract

This thesis studies the behavior of 4-(5,6,7,8-tetrahydronaphthalen-2-yl) phthalazin-1(2H)-one towards some electrophiles and nucleophiles and evaluate their antimicrobial activities and antifungal activities .
The thesis consists of the following parts:
1- Summary
2- Introduction:
In this section brief literatures review of the different methods of preparation and the reactions of phthalazine derivatives.
3- Results and Discussion:
It deals with the discussion of the experimental methods adopted for the synthesis of the designed compounds as well as their different analytical methods applied for the characterization of the new compounds.
Schemes (1-2) illustrate the synthetic pathways followed in the preparation of target compounds.
In this part the author synthesis 4-(5,6,7,8-tetrahydronaphthalen-2-yl) benzoic acid (1) by the reaction of 1,2,3,4-tetrahydronaphalene with phthalic anhydride under Friedel Craft’s condition. Condensation of benzoic acid derivative (1) with hydrazine hydrate in boiling ethanol afforded the target compound 4-(5,6,7,8-tetrahydronaphthalen-2-yl) phthalazin-1(2H)-one (2).

I. Behavior of 4-(5,6,7,8-tetrahydronaphthalen-2-yl) phthalazin-1(2H)-one (2) towards carbon electrophiles (Scheme 1):
1. Reaction with benzoyl chloride:
When phthalazinone (2) and benzoyl chloride was heated under reflux for 24h the product obtained was identified as 2-benzoyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (3) .
2. Reaction with allyl bromide:
When the phthalazinone (2) was heated under reflux for 24h with allyl bromide, the product obtained was identified as 2-allyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (4).
3. Reaction with 2-chloroethanol:
The phthalazinone (2) was heated under reflux for 24h with 2-chloroethanol, the product obtained was identified as 2-(2-hydroxyethyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl) phthalazin-1(2H)-one (5) On other hand , the structure of (5) was established chemically via the interaction with : (a) phenol and afforded 2-(2-hydroxyphenethyl)-( 5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (6a).
(b) Catachol and afforded 2-(3,4-dihydrhydroxyphenethyl)-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (6b) . Treating compound (6b) with acetic anhydride gave 4-(2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-yl) phthalazin-1(2H)-yl)ethyl)-1,2-phenylene diacetate (7) .
4. Reaction with phenyl isothiocyanate:
When phthalazinone (2) and phenyl isothiocyanate were refluxed for 6h in benzene the product obtained was identified as 1-oxo-N-phenyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)carbothiomide (8) .
5. Reaction with ethanolamine .
When the phthalazinone (2) was heated under reflux with ethanolamine, the product obtained was identified as 2-(2-aminoethyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (9) Compound (9) was verified through spectral analysis and was conducted to a series of reactions for confirming the presence of the (-NH2) ,
a) Reaction with piperonaldehyde : When the phthalazinone derivative (9) was allowed to react with piperonaldehyde in ethanol afforded the carbothiomide derivative (10) .
b) Reaction with acetic anhydride : When the phthalazinone derivative (9) was allowed to react with acetic anhydride in ethanol afforded the acetamide derivative (11) .
c) Reaction with phenyl isothiocyanate: When the phthalazinone derivative (9) was allowed to react with phenyl isothiocyanate in ethanol afforded the phenylthiourea derivative (12) .On other hand, the structure of (12) was established chemically via the interaction with diethylmalonate and afforded : 1-2(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)yl)ethyl)-3-phenyl-2-thioxo hydropyrimidine-4,6(1H,5H)-dione (13)

6. Reaction with epichlorohydrin
When the phthalazinone (2) was heated under reflux for 24h with epichlorohydrin, the product obtained was identified as 2-(oxiran-2-yl methyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (14) . After verifying the validity of the compound (14) through spectral analysis, it was conducted to some (oxirane) reactions (scheme 2 ) :
a) Reaction with hydrazine hydrate : When the phthalazinone derivative (14) was heated under reflux for 3h with hydrazine hydrate in ethanol, afforded 2-(3-hydrazinyl-2-hydroxypropyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (15) .
b) Reaction with 4-amino benzoic acid: When the phthalazinone derivative (14) was heated under reflux for 3h with 4-amino benzoic acid in ethanol afforded :4-(2-hydroxy-3-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)-yl) propyl amino)benzoic acid (16) .
c) Reaction with o-phenylenediamine: When the phthalazinone derivative (14) was heated under reflux for 3h with o-phenylene diamine in ethanol afforded : 2-(3-(2-aminophenylamino)-2-hydroxypropyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (17) . On the other hand condensation of compound (17) with aromatic aldehydes, namely, 1-naphthaldehyde and 2-hydroxybenzaldehyde in absolute ethanol afforded the corresponding Schiff’s bases (18a,b) respectively.
7. Reaction with pipreidine .
When the phthalazinone (2) was heated under reflux for 3h. with pipreidine , formaldehyde and drops of conc.HCl in ethanol , the product obtained was identified
as 2-(pipreidin-1-ylmethyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)-one (19) .
8. Reaction with phosphorous pentasulphide (P2S5 ).
Phthalazinone (2) was heated under reflux for 1h. with P2S5, in dry xylene afforded 4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-1(2H)-thione (2). The structure of the thione (20) was established chemically via the interaction with :
a) Hydrazine hydrate and afforded 1-hydrazinyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2-dihydrophthalazine (21).
b) 4-Methoxybenzaldehyde and afforded 1-(2-(4-methoxybenzylidene) hydrazinyl) -4-(5,6,7,8-tetrahydronaphthalen-2-yl) -1,2-dihydrophthalazine (22).
9. Reaction with N-ethoxycarbonylpiperazine .
When the phthalazinone (2) was heated under reflux for 3h with N-ethoxycarbonylpiperazine, formaldehyde and conc.HCl in ethanol the product obtained was identified as ethyl-4-((1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-yl)methyl)piperazine-1-carboxylate (23) .
10. Reaction with ethyl chloroacetate.
Phthalazinone (2) was treated with ethylchloroacetate afforded the corresponding phthalazine acetic acid ethyl ester (24). The structure of the ester (24) was established chemically via the interaction with a) thiosemicarbazide and afforded ethyl 2-(5´-mercapto-4-(5,6,7,8-tetrahydronaphthalen-2-yl-2H-spiro[phthalazine-1,3´-[1,2,4]triazole]-2-yl)acetate (25) . b) Hydrazine hydrate and afforded 2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-acetohydrazide (26) .
11. Reaction with ethyl cyanoacetate.
When the phthalazinone (2) was heated under reflux for 3h with ethyl cyanoacetate afforded ethyl 3-amino-3-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-yl)acrylate (27). On the other hand, the structure of the acrylate (27) was established chemically via the interaction with phenyl hydrazine and afforded 3-amino-3-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-yl)-N´-phenylacrylohydrazide (28).
II. Behavior of 2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-acetohydrazide(26). towards carbon electrophiles (Scheme 2 ) :

1. Reaction with benzoyl chloride.
When the hydrazide derivative (26) was allowed to react with benzoyl chloride in dry pyridine it yielded :N -(2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl) phthalazine-2(1H)-yl)acetyl) benzohydrazide (29) . The compound (26) is cyclised to the corresponding oxadiazolo phthalazinone (30) by the reaction with benzoyl chloride in pyridine was refluxed for 1h. then poured on ice and hydrochloric acid .
2. Reaction with phthalic anhydride .
When the hydrazide derivative (26) was heated under reflux on water bath at 150ºC for 1h. with phthalic anhydride yielded N-(1,3-dioxoisoindolin-2-yl)-2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-yl)acetamide (31) .
3-Reaction with aromatic aldehydes.
To get a new series of expected biologically active Schiff’s bases it was of interest to condense the hydrazide (26) with different aromatic aldehydes namely benzaldehyde , 4-methoxybenzaldehyde (anisaldehyde) , and 1-naphthaldehyde in boiling ethanol to give the corresponding Schiff’s bases (32a-c ) respectively. Thus when N’-(naphthalene-1-ylmethylene)-2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazine-2(1H)-yl)acetohydrazide (32c) reacted with thioglycollic acid in dry benzene and was left aside at room temperature for 24h afforded the corresponding derivative (33). On the other hand when compound (32c) was heated under reflux for 3h. with thioglycolic acid afforded the derivative (34( . Reaction of compound (32c)
with 2-aminothiophenol gave N´-((2-aminophenylthio)(naphthalene-1-yl)methyl)-2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)-yl)acetohydrazide (35) .
4-Reaction with glucose.
When the hydrazide derivative (26) was heated under reflux for 3h.with glucose it yielded acetohydrazide (36). On other hand , upon treatment (36) with acetic anhydride in ethanol afforded : 2R,3R,4R,5S,E)-6-(2-(2-(1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)-yl)acetyl)hydrazono)hexane-1,2,3,4,5pentyl penta acetate (37) .
5-Reaction with thiourea .
When the hydrazide derivative (26) was heated in oil bath with thiourea yielded : 4-(5,6,7,8-tetrahydronaphthalen-2-yl)-2-((5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)phthalazin-1(2H)-one (38) .
6-Reaction with phenyl isothiocyanate .
The hydrazide derivative (26) reacted with phenyl isothiocyanate to give the corresponding thiocarbamate derivative (39). The thiocarbamate derivative (39) was treated with sodium hydroxide to give the corresponding triazole derivative (40) , while it was cyclized to the corresponding thiadiazole derivative (41) by using conc. sulfuric acid .

7-Reaction with carbon disulphide.
Upon reacting (26) with carbon disulphide gave the cyclised product : 4-(5,6,7,8-tetrahydronaphthalen-2-yl)-2-((5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)methyl) phthalazin-1(2H)-one (42) .
8-Reaction with potassium thiocyanate .
The hydrazide derivative (26) reacted with potassium thiocyanate and gave the hydrazinecarbothioamide (43) .
9-Reaction with ethyl acetoacetate.
The hydrazide derivative (26) was heated under reflux for 3h with ethyl acetoacetate gave the ethyl 3-((2-1-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-2(1H)-yl)acetyl)diazenyl)butanoate (44) . while the (26) was heated under reflux for 9h. afforded the pyrazole derivative (45( .
10-Reaction with acetyl acetone
When the hydrazide derivative (26) was heated under reflux for 3h with acetyl acetone gave the 2-(2-oxo-2-((4-oxopentan-2-yl)diazenyl)ethyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)phthalazin-1(2H)-one (46) . while the (26) was heated under reflux for 9h. afforded the pyrazole derivative (47( .