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Studies on the Synthesis and Reactivity of Novel Bis(5-(arylazo)benzofuran-2-yl) methanone and their Imine and Oxime Derivatives

Naqui Jahan Siddiqui1, Mohammad Idrees2 and Anuradha Korde3

1 & 2Department of Chemistry, Government Institute of Science, Nagpur (M.S.), INDIA.
3Department of Chemistry, Government Science College, Gadchiroli (M.S.), INDIA.
email:naquiphd.2010@gmail.com.

(Received on: November 5, Accepted: November 8, 2017)

Abstract

2-hydroxy-5-(arylazo)benzaldehyde (1a-d) on reaction with 1,3-dichloroketones afforded Bis(5-(arylazo)benzofuran-2-yl)methanones (2a-d) as a starting reagents. A series of Bis(5-(arylazo)benzofuran-2-yl) methanone oximes (3a-d) was synthesized in moderate to good yields from 2a-d on reaction with hydroxylamine hydrochloride in pyridine. Extending the reactions of 2b, 2c and 2d with reagents such as phenyl hydrazine, semicarbazide and thiosemicarbazide afforded 4b, 4c and 4d respectively. The structures of this synthesized compound have been satisfactorily confirmed on the basis of chemical transformation reaction, elemental and spectral data came from IR, 1H NMR and mass spectra.

Keywords:Bis(5-(aryazo)benzofuran-2-yl)methanone, semicarbazone, ketoximes, imine, and thiosemicarbazone.

Introduction

Condensed heterocyclic compounds containing different heteroatoms such as oxygen and nitrogen have attracted significant consideration as a result of their important biological actions and occurrence in a vast array of natural products. The benzofuran ring system is one of an important class of heterocyclic compound that occur in immense number of natural productsl-2, that can be isolated particularly from Machilusglaucescens, Ophryosporuscharua, Ophryosporuslorentzii, Krameriaramosissima, and Zanthoxylumailanthoidol3. The most recognized benzofurans are ailanthoidol, amiodarone, and bufuralol compounds, which possess broad range of important physiological, pharmacological and toxic properties and hence there is a continuous interest in their chemical synthesis4-5. Furthermore, benzo[b]furans are also used as building blocks for fluorescent sensors6 and are used as optical brighteners. Similarly, numerous bisheterocyclic systems have been synthesized7-10 and their structures have also been suggested, but literature survey still indicates that less work is published on bisbenzofuran and its derivatives. On the other hand, biological activity studies on bisbenzofuran containing compounds were also found to be limitedl1-12. Since the last decade, oxime ethers have found to be used as nonsteroidal antinflammatory drugsl3, beta-adrenergicl4, mold inhibitory active compound in poultry sciencel5, anti-protozoanl6, insect growth regulatorl7 and as various materials with steroidal effectsl8. Previous studies, have reported the synthesis and antimicrobial activity of some bis-(benzofuran-2-yl) methanone, cyclobutane and mesitilen substituted benzofuran derivativesl9-20. Heterocycles like substituted methanone possessing interesting biological activities have stimulated considerable research work in recent years leading to the synthetic utility of the derivatives of this ring system. Encouraged by the literature survey we planned to prepare bisbenzofuran methanones containing azo linkage and their various imine derivatives by reacting it with different reagents like phenyl hydrazine, semicarbazide and thiosemicarbazide.

MATERIAL AND METHODS

Chemicals used for the synthesis were of AR grade of Merck, S.D.Fine and Aldrich. The melting points were recorded in open capillary in paraffin bath and are uncorrected. IR spectra were recorded on a Shimadzu IR Spectrophotometer (KBr, v max in cm-1). Positive-ion Electro Spray Ionization (ESI) mass spectra were obtained with a Waters Micromass Q–TOF Micro, Mass Spectrophotometer. 1H NMR spectra are recorded on a Bruker AM 400 instrument (400 MHz) using tetramethylsilane (TMS) as an internal reference and DMSO-d6 as solvent. Chemical Shifts are given in parts per million (ppm). Elemental (CHN) analysis was done using Thermo Scientific (Flash-2000), the compounds were analyzed for carbon, hydrogen and nitrogen and the results obtained are in good agreement with the calculated values. The reactions were monitored by E. Merck TLC aluminum sheet silica gel 60 F254 and visualizing the spot in UV Cabinet and iodine chamber.

EXPERIMENTAL

Aryl primary amines such as p-toluidine (a), m-anisidine (b), p-bromo aniline (c), p-anisidine (d) as starting material were used for diazotization for the synthesis of 2-hydroxy-5-(arylazo)benzaldehyde (1a-d) following the available literature procedure. The structural identities were confirmed on the basis of physical data as in table 1 and spectral data is given below.

Spectral analysis of 2-hydroxy-5-(p-tolylazo)benzaldehyde (1a)23:IR cm-1: 3185(-OH), 3030 (ArH), 2918. 2994 (-CH3), 1655 (C=O), 1619,1602,1479 (-C=C-), 2742 (C-H str. in -CHO), 1500,1575 (-N=N-) 1H NMR (DMSO-d6) δ ppm: 11.41(s, 1H, -OH), 10.37(s, 1H, -CHO), 2.4(s, 3H, -CH3), 7.18-8.18 (m, 7H, ArH); MS: 241[M+1]+ Elemental analysis Calcd.For C14H12N2O2: C, 70.00; H, 5.00; N, 11.76 Found: C, 69.91; H, 4.93; N, 11.82

Table-1: Physical data of the synthesized compounds

Entry R Colour Recry.Solvent m.pt.ᵒC % Yield Rf m.f.
la 4-CH3 Yellow Acetic acid 152-154 68.25 0.72 C14H12O2N2
lb 3-OCH3 Brown Acetic acid 98-100 75.58 0.68 C14H12O3N2
lc 4-Br Yellow Acetic acid 112-113 69.25 0.64 C13H9O2N2Br
ld 4-OCH3 Brown Acetic acid 110-112 82.32 0.71 C14H12O3N2

Procedure for the synthesis of Bis(5-(arylazo)benzofuran-2-yl)methanones (2a-d):In 100 mL round bottom flask, 1a (5 mmol) and 30 mL anhydrous acetone were taken. To this solution 1,3-dichloro acetone (5 mmol ) and potassium carbonate (5 mmol ) was added and refluxed for 6h. Later the reaction mixture was poured in crushed ice, the precipitate so obtained was filtered and washed with water and recrystallized from suitable solvent (Scheme 1). Similarly, 2b-d were synthesised from 1b-d by extending the same procedure followed for 2a, the physical data of all synthesized compounds are furnished in table 2.

Table-2: Physical data of the synthesized compounds

Entry R Colour Recry.Solvent m.pt.ᵒC % Yield Rf m.f.
2a 4-CH3 Yellow DMF 285-288 71.47 0.58 C31H22O3N4
2b 3-OCH3 Yellow DMF 238-240 62.90 0.65 C31H22O5N4
2c 4-Br Yellow DMF 324-326 56.82 0.64 C29H16O3N2Br
2d 4-OCH3 Yellow DMF 273-275 52.72 0.62 C31H22O5N4

Procedure for the synthesis of Bis(5-(arylazo)benzofuran-2-yl)methanone oximes (3a-d):2a (3.3 mmol) was dissolved in pyridine (20 mL) in a round bottom flask. Then hydroxylamine hydrochloride (3.33 mmol) was added and the reaction mixture was refluxed for 2h. Afterwards it was poured in crushed ice, the precipitate so obtained was filtered, washed with water and recrystallized from DMF to get 3a (Scheme 3). Similarly, 3b--d were synthesised from 2b-d by extending the same procedure applied for 3a, the physical data of all synthesized compounds are summarized in table 3.

Spectral analysis of Bis(5-(p-tolylazo)benzofuran-2-yl)methanone oxime (3a):IR cm-1: 3183, 3101(-N-OH), 3025(ArH), 2850,2919 (CH3), 1649 (C=N), 1500,1550 (-N=N-), 1602, 1613, 1581,1466 (C=C str.), 1279,1265 (C-O-C sym. str.),1022,1098 (C-O-C asym. str.); 1H NMR (DMSO-d6) δ ppm: 13.22 (s, 1H, -OH of =N-OH ), 2.43 (s, 6H, two -CH3 group ), 7.40- 8.36 (m, 16H, ArH,) MS: 514[M]+, 515[M+1]+, Elemental analysis Calcd. For C31H23O3N5: C,72.50, H,4.51, N,13.64 Found: C, 72.072, H, 5.171, N, 13.145.

Table-3: Physical data of the synthesized compounds

Entry R Colour Recry.Solvent m.pt.ᵒC % Yield Rf m.f.
3a 4-CH3 Yellow DMF 310-312 61.73 0.46 C31H23O3N5
3b 3-OCH3 Yellow DMF 222-224 76.14 0.51 C31H23O5N5
3c 4-Br Yellow DMF 270-272 72.09 0.65 C29H17O3N5Br
3d 4-OCH3 Yellow DMF 286-288 54.59 0.59 C31H23O5N5

Procedure for the synthesis of Bis(5-(m-methoxyphenylazo)benzofuran-2-ylmethylene)- 2-phenylhydrazine (4b): 2b (1.43 mmol) was dissolved in DMF (20 mL) in a round bottom flask. Then phenyl hydrazine (1.43 mmol) and few drops of acetic acid were added and the reaction mixture was refluxed for 2h. Then it was poured in crushed ice, the precipitate so obtained was filtered, washed with water and recrystallized from suitable solvent (Scheme 3).

Procedure for the synthesis of Bis(5-(p-bromophenylazo)benzofuran-2-ylmethylene) semicarbazide (4c): 3c (3.27 mmol) was dissolved in DMF (20 mL) in a round bottom flask. Then semicarbazide (3.27 mmol) and pyridine in (25 mL) were added and the reaction mixture was refluxed for 2h. Then it was poured in crushed ice, the precipitate so obtained was filtered, washed with water and recrystallized from suitable solvent (Scheme 3).

Procedure for the synthesis of Bis(5-(p-methoxyphenylazo)benzofuran-2-ylmethylene) thiosemicarbazide (4d) : 2d (3.27 mmol) was dissolved in pyridine (20 mL) in a round bottom flask. Then thiosemicarbazide (3.27 mmol) and reaction mixture was refluxed for 2h. Then it was poured in crushed ice, the precipitate so obtained was filtered, washed with water and recrystallized from suitable solvent (Scheme 3). The physical data of all synthesized compounds are summarized in table 4.

Table-4: Physical data of the synthesized compounds

Entry R R' Colour Recry.Solvent m.pt.ᵒC % Yield Rf m.f.
4b 4-CH3 -C6H5 Yellow DMF <280oC 77.87 0.54 C37H28O4N6
4c 3-OCH3 -CONH2 Yellow DMF 275-277 80 0.41 C30H19O3N7
4d 4-OCH3 -CSNH2 Yellow DMF 278-280 67.21 0.43 C32H25O4N7

RESULT AND DISCUSSIONS

The synthesis of the novel compounds (2a-d and 3a-d) is described in the above reaction schemes. The identities of the newly synthesized compounds have been established on the basis of their elemental analysis and IR, 1H NMR and Mass spectral data24. Diazotization of four aryl primary amines (a-d) afforded (1a-d). The significant bands in the FT-IR spectra are those due to the azo chromophore (-N=N-), C-N stretching and strong bands due to the aromatic region in the range of 1400-1600 cm-1 are also significant as azo bond stretching appears between the bands of the aromatic region. The IR spectra of the dye 1a showed prominent azo bond (-N=N-) vibrations which are identifiable between 1500 cm-1 and 1575 cm-1. The absorption band of the azo chromophore is clearly distinct from the C=C absorption bands. Due to aromatic region, the higher energy bands appeared from 1407 cm-1 to 1479 cm-1 while the lower energy bands ranged from 1500 cm-1 to 1619 cm-1. The absorption of C-N is also observed as supporting evidence and its frequency ranges from 1206 cm-1 to 1353 cm-1. Similarly, the 1H NMR spectrum showed multiplet in the range of δ 7.18 to 8.18 ppm due to seven protons confirms the formation of 1a which was further confirmed by mass spectrum with a molecular ion peak at m/z 241[M+1]+, is in agreement with the molecular formula C14H12O2 (Scheme1).
Refluxing 2-hydroxy-5-(arylazo)benzaldehydes (1a-d) with 1,3-dichloroacetone in presence of potassium carbonate afforded substituted (2a-d). Formation of (2a-d) was proved by the FeCl3 test that was found to be negative and this was also proved by the DNP test that was found to be positive. Refluxing (2a-d) with hydroxylamine hydrochloride afforded (3a-d). The formation of (3a-d) was confirmed by the DNP test that was found to be negative. IR spectra of 3a showed absorption bands at 3183 cm-1 for -OH of (-NOH) group and 1649 cm-1 for (C=N). The 1H NMR spectra of 3a showed a characteristic peak at δ 13.22 (s, 1H, -OH), 2.41 (s, 6H, two -CH3 group), δ 7.40-8.36 (m, 16H, Ar-H) and [M]+ in mass spectra at 514 [M]+ and 515 [M+H]+ confirms the formation of 3a having the molecular formula C31H23O3N. The percentage of elements corresponding to C, H and N, were found to be in good agreement with the calculated values for 3a. On the basis of chemical transformation reaction and physical data the synthesized compounds 4b, 4c and 4d, were confirmed.

Conclusion

Arylazosalicyladhydes (1a-d), four novel bisketones (2a-d) and their imine derivatives (3a-d, 4b, 4c, and 4d) containing azo linkage were prepared in the moderate to good yield. The structures of the compounds were confirmed on the basis of physicochemical, spectral and the elemental analysis data.

Acknowledgements

The authors are thankful to the Director, Institute of Science, Nagpur, Principal, Government Science College, Gadchiroli, research scholars Mr. Roshan Nasare and Mr. Satish Kola for their support and cooperation. The authors are also thankful to the Director, SAIF, Punjab University, Chandigarh for providing CHN analysis, IR, 1H NMR and Mass Spectra.

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