Synthesis of Some Unsymmetrical Dioxime Esters Using the Acetylacetone as a Precursor

Three unsymmetrical dioxime esters (2E,4E)-(4-imino O-benzoyl-2-imino O-terphthaloyl)pentane, (2E,4E)-(4-imino O-benzoyl-2-imino O-tosyl)pentane and (2E,4E)-(4-imino O-terphthaloyl-2-imino O-tosyl)pentane were obtained employing esterification process between (2E,4E)-pentane-2,4-dione O4-benzoyl dioxime 2 and terephthaloyl chloride or tosyl chloride. The third unsymmetrical dioxime ester was synthesized through similar esterification reaction between 4-(2E,4E)-4-(hydroxyimino)pentan-2-ylideneaminooxycarbonyl)benzoyl chloride 8 and tosyl chloride. The yields of these esterification reactions has been found to vary from moderate to very good yields giving single geometric isomers in all cases. The synthesis of these three unsymmetrical dioxime esters required, firstly, the synthesis of (2E,4E)-pentane-2,4-dione O4-benzoyl dioxime and 4- [(2E,4E)-4-(hydroxyimino)pentan-2-ylidene]amino oxycarbonylbenzoyl chloride as two precursors. The analytical data that was collected from the IR, mass spectrometry and the 1 HNMR respectively revealed that the (2 E ,4 E )-(4-imino O -benzoyl-2-imino O -terphthaloyl)pentane 4 and the (2 E ,4 E )-(4-imino O -benzoyl-2-imino O -tosyl)pentane 6 were formed. The 1 HNMR spectroscopic data confirmed the formation of single geometric isomer in both cases.


Introduction
Oximes have been classified as useful molecules for protecting and purifying carbonyl compounds in organic chemistry [1]. These molecules have also shown antimicrobial, antioxidant, antitumor, antidepressive, antiviral agents and anticonvulsant properties [2][3][4][5][6][7]. Oximes have been reported to be good precursors for the synthesis amines that are used as paints, fibers, medical tools and in the synthesis of some lactams [8][9][10][11]. Oxime esters could be obtained by the reaction of keto-or aldoximes with acid chlorides or acid anhydrides. The oxime esters could also be used in the synthesis of peptides and fragrances [12,13]. Oxime esters have also been reported to have cleavage impact on DNA [14][15][16], herbicidal as well as antitumor activities [17,18]. Oxime esters are important intermediates for the synthesis of biologically active heterocyclic molecules [19]. Herein, unsymmetrical dioxime esters (2E,4E)-

Materials
Acetyl acetone, hydroxylamine hydrochloride, benzoyl chloride, terphthaloyl chloride, p-toluene sulphonyl chloride, potassium carbonate, anhydrous sodium sulphate, triethylamine and chloroform were purchased from P K Park and used without further purification.

Instrumentation
Melting points were measured on a Barnstead electrothermal IA 9100. 1 HNMR spectrum was recorded on a Bruker Avance 300 spectrometer. Residual proton signal from the deuteriated solvent was used as reference [DMSO ( 1 H, 2.50 ppm)]. Infrared spectrum was recorded on Jasco FT/IR-4100 Fourier transform infrared spectrometer. Mass spectrum was recorded on a Micromass Autospec M spectrometer.

Synthesis of (E)-4-(Hydroxyimino) Pentan-2-One
An literature procedure [20] was followed for the synthesis of the entitled compound. Hydroxylamine hydrochloride (6.94 g, 100 mmol), acetyl acetone (10 g, 100 mmol) and potassium carbonate (13.80 g, 100 mmol) in the presence of anhydrous sodium sulphate (14.20 g, 100 mmol) were placed in a mortar and ground at room temperature for 30 min. Chloroform (20 cm 3 ) was then added to the resulting paste, filtered and the solvent was evaporated in vacuo. The desired mono ketoxime was obtained, as two isomeric forms (E)-4-(hydroxyimino)pentanone and (Z)-4-(hydroxyimino)pentan-one in ratio of (9:1), in low yield (3.10 g, 26.95 mmol, 27%) as yellow oil. The product was clean enough to be taken into the next synthetic step. IR  max (cm

Synthesis of (E)-4-(4-Oxopentan-2-Iminocarbonyl) Benzoyl Chloride 7
An literature procedure [20] was followed for the synthesis of the entitled compound. (E)-4-(hydroxyimino)pentan-2-one (3.45 g, 30.0 mmol) in chloroform (40 cm 3 ) in the presence of triethyl amine (4.04 g, 40.0 mmol) were placed in a round-bottomed flask and stirred at 0 -7 °C. A solution of terphthaloyl chloride (6.52 g, 32.0 mmol) in chloroform (50 cm 3 ) was then added dropwise over 30 min. The reaction mixture was left stirring at room temperature for 2 hours, after which a distilled water (30 cm 3 ) was added to the mixture and stirred for further 10 min. The organic layer was extracted, dried over anhydrous Na 2 SO 4 and filtered. The solvent was evaporated in vacuo to obtain the desired oxime ester 7 in moderate yield (3.

Synthesis of (2E,4E)-(4-imino O-Benzoyl-2-Imino O-Terphthaloyl) Pentane 4
An literature procedure [20] was followed for the synthesis of the entitled compound. The mono oxime benzoyl mono ester 2 was prepared first to be the precursor for the synthesis of compound 4. Hydroxylamine hydrochloride (2.08 g, 30 mmol), mono oxime mono benzoyl ester 1 (6.57 g, 30 mmol) and potassium carbonate (4.14 g, 30 mmol) in the presence of anhydrous sodium sulphate (4.26 g, 30 mmol) were placed in a mortar and ground at room temperature for 30 min. Chloroform (20 cm 3 ) was then added to the resulting paste, filtered and the solvent was evaporated in vacuo. The desired dioxime mono benzoyl ester 2 was obtained in moderate yield (3.20 g, 13.67 mmol, 46%) as yellow oil. This was taken in the next step, as is, to synthesize the desired (2E,4E)-(4-imino Obenzoyl-2-imino O-terphthaloyl)pentane 4. Thus, the dioxime mono benzoyl ester 2 (3.0 g, 12.82 mmol) was dissolved in chloroform (40 cm 3 ) in the presence of triethyl amine (1.29 g, 12.82 mmol) were placed in a roundbottomed flask and stirred at 0 -7 °C. A solution of terphthaloyl chloride (2.60 g, 12.82 mmol) in chloroform (50 cm 3 ) was then added dropwise over 30 min. The reaction mixture was left stirring at room temperature for 2 hours, after which distilled water (30 cm 3 ) was added to the mixture and stirred for further 10 min. The organic layer was extracted, dried over anhydrous Na 2 SO 4 and filtered. The solvent was evaporated in vacuo to obtain the desired oxime esters 4 in a very good yield (4.10 g, 10.23 mmol, 80%) as brown oil. The product did not require further purification. IR  max (cm −1 ) 2980 (C-H

Synthesis of (2E,4E)-(4-Imino O-Benzoyl-2-Imino O-Tosyl) Pentane 6
An literature procedure [20] was followed for the synthesis of the entitled compound. The mono oxime benzoyl mono ester 2 was prepared first to be the precursor for the synthesis of compound 4. Hydroxylamine hydrochloride (2.08 g, 30 mmol), mono oxime mono benzoyl ester (6.57 g, 30 mmol) and potassium carbonate (4.14 g, 30 mmol) in the presence of anhydrous sodium sulphate (4.26 g, 30 mmol) were placed in a mortar and ground at room temperature for 30 min. Chloroform (20 cm 3 ) was then added to the resulting paste, filtered and the solvent was evaporated in vacuo. The desired dioxime mono benzoyl ester 2 was obtained in moderate yield (3.20 g, 13.67 mmol, 46%) as yellow oil. This was taken in the next step, as is, to synthesize the desired (2E,4E)-(4-imino Obenzoyl-2-imino O-tosyl)pentane 6. Thus, the dioxime mono benzoyl ester 2 (3.0 g, 12.82 mmol) wa dissolved in chloroform (40cm 3 ) in the presence of triethyl amine (1.29 g, 12.82 mmol) were placed in a round-bottomed flask and stirred at 0 -7 °C. A solution of p-toluene sulfonyl chloride (2.44 g, 12.82 mmol) in chloroform (50 cm 3 ) was then added dropwise over 30 min. The reaction mixture was left stirring at room temperature for 2 hours, after which distilled water (30 cm 3 ) was added to the mixture and stirred for further 10 min. The organic layer was extracted, dried over anhydrous Na 2 SO 4 and filtered. The solvent was evaporated in vacuo to obtain the desired oxime esters 6 in a good yield (3.50 g, 9.02 mmol, 70%) as dark brown oil. The product did not require further purification. IR

Synthesis of (2E,4E)-(4-Imino O-Terphthaloyl-2-Imino O-Tosyl)Pentane 10
An literature procedure [20] was followed for the synthesis of the entitled compound. The mono oxime terphthaloyl mono ester 8 was prepared first to be the precursor for the synthesis of compound 10. Hydroxylamine hydrochloride (1.48 g, 21.30 mmol), (E)-4-(4-oxopentan-2-iminocarbonyl) benzoyl chloride 7 (5.99 g, 21.30 mmol) and potassium carbonate (2.93 g, 21.30 mmol) in the presence of anhydrous sodium sulphate (3.02 g, 21.30 mmol) were placed in a mortar and ground at room temperature for 30 min. Chloroform (20 cm 3 ) was then added to the resulting paste, filtered and the solvent was evaporated in vacuo. The desired dioxime mono terphthaloyl ester 8 was obtained in moderate yield (2.60 g, 8.76 mmol, 41%) as light yellow oil. This was taken in the next step, as is, to synthesize the desired (2E,4E)-(4-imino O-benzoyl-2-imino O-tosyl)pentane 10. Thus, the mono oxime terphthaloyl mono ester 8 (2.49 g, 8.40 mmol) was dissolved in chloroform (40 cm 3 ) in the presence of triethyl amine (0.84 g, 8.40 mmol) were placed in a round-bottomed flask and stirred at 0 -7 °C. A solution of p-toluene sulfonyl chloride (1.60 g, 8.40 mmol) in chloroform (50 cm 3 ) was then added dropwise over 30 min. The reaction mixture was left stirring at room temperature for 2 hours, after which distilled water (30 cm 3 ) was added to the mixture and stirred for further 10 min. The organic layer was extracted, dried over anhydrous Na 2 SO 4 and filtered. The solvent was evaporated in vacuo to obtain the desired oxime ester 10 in moderate yield (2.0 g, 4.43 mmol, 53%) as dark brown oil. The product could be purified by column chromatography using an eluent of ethyl acetate and petroleum ether in ratio of (3:1 v/v). IR  max (cm