R. Kumar, M. Imam, M. Singh
Oct 1, 2020
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Journal of emerging technologies and innovative research
Abstract
A series of 2-substituted naphtho[1,2-d]oxazole derivatives have been synthesized from 1-amino-2-naphthol hydrochloride as common substrate. For synthesis of 2-methylnaphtho[1,2-d]oxazole and 2phenylnaphtho[1,2-d]oxazole we have employed carboxylic acid derivatives, namely acetic anhydride and benzoyl chloride respectively. Other 2-substituted naphto[1,2-d]oxazole derivatives have been synthesised from substituted aromatic aldehydes. In spite of evidences of solvent assisted thermal dehydrogenation of dihydroxazole ring, we have employed DDQ for dehydrogenation. All these compounds were characterized by FT-IR, ‘HNMR and elemental analysis. Key word: Naphthoxazole, heterocyclic synthesis, DDQ, Biological properties. INTRODUCTION: Benzoxazole and naphthoxazole are a heterocyclic compounds, used in research as a starting material for the synthesis of larger, usually bioactive structures. Many derivatives of benzoxazoles are comercially important. These compounds possess potent biological (Devinder K, et al., 2002) and photochromatic activities. 2substituted naphthoxazole is a major subunit occurring in natural products (Rodriguez A D, et al., 1999). Orthosubstituted naphthoxazole derivatives show promising inhibitory activity for protein tyrosine phosphatase-1B (PTB-1B) and in vivo antidiabiabetic activity(Kumar A, et al., 2009; Malamas M S, et al., 2000; Malamas M S, et al., 2000;). Benzoxazole and naphthoxazole derivatives possessing antifungal (Ertan T, et al., 2009), anti-inflammatory (Dunwell D W,et al., 1977), antitumour (White A W, et al., 2004) and anti H.I.V.(Novelli F, et al., 1997) activities have been reported. The benzoxazole derivatives are used as fluorescent probes (Xu Y, et al., 2010; Kim TI et al., 2009) and sensors for the detection of different metal ions (Chem W, et al., 2012; Yan L, et al., 2012). Our present endevour is to prepare 2-substituted naphtho[1,2-d]oxazole derivatives from different routes as there are chances of these being biologically active. © 2020 JETIR October 2020, Volume 7, Issue 10 www.jetir.org (ISSN-2349-5162) JETIR2010228 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1762 EXPERIMENTAL: All the chemicals and solvents used in syntheses were obtained from CDH, Sigma Aldrich and Merck chemical companies and used without further purification. Precoated silica gel plates (Kieselgel 60 F254, Merck), were used for TLC and visualised with UV light, (max = 254 nm), for monitoring the progress of reactions. Melting points were determined in open capillary tube by using Elico instrument and readings are uncorrected. IR spectrum was recorded in Shimadzu FT-IR spectrophotometer with KBr disc. The results of elemental analysis of C, H and N were obtained for all compounds on a Carlo-Erba EA 1108 elemental analyser. Dry solvents were prepared by using pre heated molecular seives 3 Å or 4 Å whichever applicable. Refluxing was carried out using silicone oil bath and CaCl2 guard tube. Experimental procedure for the synthesis of 2-Methylnaphtho[1,2-d]oxazole (5) 1-amino-2-naphthol hydrochloride (1, 0.98 g, 0.005 mole) added 6 mL of cold hydrochloric acid and stirred. Introduced a solution of 5 g of sodium acetate in 25 ml of water, followed by 5 mL of acetic anhydride (2). Shaken the mixture in cold until the smell of acetic anhydride disappeared. Filtered and the residue washed with cold aqueous ethanol, dried in vacuum. Dry product was refluxed in nitrobenzene for 3 hours maintaining the temperature 180-190C. Progress of reaction was monitored with TLC (silica gel plates) using EtOAc/Hexane (5:3). Excess solvent was removed by steam distillation and allowed to cool. Crystallization from benzene + ethyl acetate (1:2) in cold afforded pure 2-methylnaphtho[1, 2-d]oxazole (5, 0.66 g, 72%). Experimental procedure for the synthesis of 2-Phenylnaphtho[1,2-d]oxazole (7) 1-amino-2-naphthol hydrochloride (1, 0.98 g, 0.005 mole) was taken in Sodium hydroxide solution, stirred at room temperature. Benzoyl chloride (3, 1.05 g, 0.0075 mole) was added drop wise with constant shaking, venting and cooling until the odour of benzoyl chloride had disappeared. Filtered the residue, washed with cold ether and dried in vacuum. Dry product (1.02 g, 78%) was taken in chlorobenzene and refluxed on oil bath at 110 –130 C for 2.5 hours. Excess solvent was removed by distillation in vacuum and crude was allowed to cool at room temperature. Crystallization from methyl ethyl ketone afforded 2-phenylnaphtho[1,2d]oxazole (6, 0.82g, 67%). © 2020 JETIR October 2020, Volume 7, Issue 10 www.jetir.org (ISSN-2349-5162) JETIR2010228 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1763 8, R= O-OH.C6H4 12, R= O, p-Cl2.C6H3 9, R= m-OH.C6H4 13, R= O-NO2.C6H4 10, R= O-Cl.C6H4 14, R= m-NO2.C6H4 11, R= p-Cl.C6H4 15, R= p-NO2.C6H4 Scheme 1. Synthesis of 2-substituted naphto[1,2-d]oxazole derivatives (6-15) General experimental procedure for the synthesis of 2-(substituted phenyl)naphtho[1,2d]oxazole derivatives (8-15) 1-amino-2-naphthol hydrochloride (1, 0.98g, 0.005 mole) and corresponding aromatic substituted aldehyde (4, 0.005 mole) were refluxed in DMF at 140 –155 C up to the completion of reaction (10-15 h). Progress of reaction was monitored with TLC using EtOAc/Hexane. Reaction mixture was cooled at room temperature. DDQ (5, 1.13g, 0.005 mole) added in reaction mixture and temperature was maintained at 145 –155 C for 2-3 hours. The reaction mixture was cooled and solvent evaporated under vacuum. Crud was washed with water and recrystallized to afford corresponding compounds (8-15) in 54-73% yield. © 2020 JETIR October 2020, Volume 7, Issue 10 www.jetir.org (ISSN-2349-5162) JETIR2010228 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1764 Report of FT-IR spectral data Compound No. Description Frequency: (cm) 6 2-methylnaphtho[1,2-d]oxazole 2960, 2860 (-CH3 stretching), 3050 (Aromatic –CH stretching), 1600, 1585 (Aromatic C=C stretching), 1550 (Aromatic C=N stretching), 1150 (C-C stretching) 7 2-phenylnaphtho[1,2-d]oxazole 3040,(Aromatic -CH stretching), 1615 (C=C ring stretching), 1576 (C=N stretching), 1216, 1126 (C-O stretching), 1160 (C-C stretching) 8 2-(Naphtho[1,2-d]oxazol-2-yl)phenol 3364,3351(-OH stretching), 3045 (Aromatic –CH stretching), 1626 (C=C ring stretching), 1574 (C=N ring stretching), 1215,1126 (C-O stretching) 9 3-(Naphtho[1,2-d]oxazol-2-yl)phenol 3375, 3355(-OH stretching), 3055 (Aromatic –CH stretching), 1628,1563 (C=C, C=N ring stretching), 1213,1134 (C-O stretching) 10 2-(2-chlorophenyl)naphtho[1,2d]oxazole 3047(Aromatic -CH stretching), 1625,1575 (C=C, C=N ring stretching), 1214,1120 (C-O stretching), 730 (-CCl stretching) 11 2-(4-chlorophenyl)naphtho[1,2d]oxazole 3056 (Aromatic -CH stretching), 1629,1560 (C=C, C=N ring stretching), 1215,1135 (C-O stretching), 732 (-CCl stretching) 12 2-(2,4-Dichlorophenyl)naphtho[1,2d]oxazole 3040 (Aromatic -CH stretching), 1615,1571 (C=C, C=N ring stretching), 1216,1122 (C-O stretching), 726 (-CCl stretching) © 2020 JETIR October 2020, Volume 7, Issue 10 www.jetir.org (ISSN-2349-5162) JETIR2010228 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1765 13 2-(2-Nitrophenyl)naphtho[1,2d]oxazole 1530, 1325 (-NO2 stretching), 3041 (Aromatic -CH stretching),1621,1572 (C=C, C=N ring stretching), 1210,1125 (C-O stretching) 14 2-(3-Nitrophenyl)naphtho[1,2d]oxazole 3045 (Aromatic -CH stretching),1628,1577 (C=C, C=N ring stretching), 1215,1130 (C-O stretching), 1533, 1327 (-NO2 stretching) 15 2-(4-Nitrophenyl)naphtho[1,2d]oxazole 1537, 1330 (-NO2 stretching), 3043 (Aromatic -CH stretching),1625,1575 (C=C, C=N ring stretching), 1211,1127 (C-O stretching) RESULT AND DISCUSSION : In the light of above mentioned synthesis approaches and our several experimental trails, we divided our synthetic scheme for substituted naphtho[1,2-d]oxazole into two categories using 1-amino-2-naphthol hydrochloride as common substrate. For synthesis of 2-methylnaphtho[1,2-d]oxazole (6) and 2phenylnaphtho[1,2-d]oxazole (7) we have employed carboxylic acid derivatives, namely acetic anhydride and benzoyl chloride respectively. Elemental analysis and spectral data indicated the correct synthesis products. H NMR spectra of title compound (6) clearly indicates that the presence of methyl group at position -2 in oxazole fragment [δ 2.64 (S, 3H)]. The H NMR spectrum of title compound (7) shows the presence of phenyl group at position2 of oxazole fragment [δ 8.36 (m, 2H), 7.70 (m, 1H), 7.57 (m, 1H)]. Title compounds (8-15) are being synthesised using a different reaction procedure. 1-amino-2-naphthol hydrochloride is the common starting material as earlier. Now the carboxylic acid derivatives are replaced by substituted aromatic aldehydes. In spite of evidences of solvent assisted thermal dehydrogenation of dihydroxazole ring, we have employed DDQ for dehydrogenation. Perusal of reaction conditions required for title compounds (8-15) emphasises one very clear cut outcome; that is, the temperature required for condensation and cyclization using different aldehydes is a function of electrophilicity of aldehyde component. © 2020 JETIR October 2020, Volume 7, Issue 10 www.jetir.org (ISSN-2349-5162) JETIR2010228 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 1766 Table1: Comparative studies on synthesis of naphtho[1,2-d]oxazoles Title compounds Number Aldehydes used Reflux condition for cyclization Yield (%) 8. CHO OH 150-55C , 14 hours 54.6