To Chemistry Journal Vol 7 (2020) ISSN: 2581-7507 https://purkh.com/index.php/tochem Overview on the chemistry of 1-(4-substituted aminophenyl) ethanones Part(I) Moustafa. A. Gouda, *1, 2 Mohamed H. Helal, 3, 4 Ahmed Ragab, 3 Ghada G. El-Bana, 5 Mohammed A. Salem, 3, 6 1Department of Chemistry, Faculty of Science and Arts, Ulla, Taibah University, KSA 2Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, 35516, Mansoura, Egypt 3Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt 4Department of Chemistry, Faculty of Arts and Science, Northern Border University, Rafha, KSA. 5 laboratory Department, Blood Bank, Student hospital, Mansoura University, El-Gomhoria Street, 35516, Mansoura, Egypt 6Department of Chemistry, Faculty of Arts and Science, King Khalid University, Mohail Assir, KSA [email protected]*, [email protected], [email protected]. Abstract: This review presents a systematic and comprehensive survey of the method of preparation and the chemical reactivity of 1-(4-substituted-aminophenyl) ethanones. The target compounds are important intermedi-ates for the synthesis of a variety of synthetically useful and novel heterocyclic systems with different ring sizes such as thiophene, oxazole, triazole, pyrimidine, pyridine, quinolone, coumarin, imidazopyrimidine, pyridoimidazole and triazolo[1,5-a] pyridine. Keywords: 1-(4-Substitutedaminophenyl)ethanones, Heterocyclic, Thiazole, Pyridine, 2- aminothiophenes Introduction There is no review summarizing the literature on the synthesis and chemistry of 1-(4- substitutedaminophenyl)ethanones. This review therefore aims to cover the work on the synthesis and reaction of 1-(4-substitutedaminophenyl) ethanone. 4-Aminophenylethanone, 1 has been a key starting material for the synthesis of formyl-substituted 5-aryl-2,2'-bithiophenes as new precursors for nonlinear optical (NLO) materials [1], 4-amino-5,6-diaryl-furo[2,3-d]pyrimidines as potent glycogen synthase kinase-3 inhibitors [2], 1-phenyl-3-{4-[(2E)-3-phenylprop-2- enoyl]phenyl-thiourea and urea derivatives with anti-nociceptive activity [3], and methane sulfonamide analogues of rofecoxib [4]. Furthermore, 4-Phenylmorpholine derivatives are showing anti-inflammatory [5, 6], central nervous system [5], and antimicrobial activities [5], antidiabetic [7], antiemetic [8], platelet aggregation inhibitors, antihyperlipo-proteinemics [7], bronchodilators, growth stimulats [9], and antidepressants [10]. Synthesis Hydrolysis of 1-ethynyl-4-nitrobenzene 2 with water in presence of AuBr3 [11], 2, 2, 2- trifluoroethanol [12], or cetyltrimethylammonim bromide/ isopropyl alcohol gave 4- aminoacetophenone 1[13]. Furthermore, treatment of N-(4-acetylphenyl)-acetamide 3 with aqueous sodium hydroxide in methanol afforded 4-aminoacetophenone [14] (Scheme 1). Moreover, reaction of triisopropylsilyl- 4-acetylphenylcarbamate 4 with tetrabutyl ammonium fluoride in tetrahydrofuran [15]. Also, hydrolysis of 5, 5, 6, 6, 7,7, 8, 8, 9, 9, 10, 10, 11, 11, 12, 12, 12-heptadecafluoro-2-methyl-dodecan-2-yl-4- acetylphenylcarbamate 5 with trifluoroacetic acid in dichloromethane[16]. 21 To Chemistry Journal Vol 7 (2020) ISSN: 2581-7507 https://purkh.com/index.php/tochem In addition, hydrolysis of (E)-1-(4-((4-(3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9, 10, 10, 10- heptadecafluorodecyl)phenyl(phenyl) methylene amino)-phenyl)ethanone 6 or 1-(4- (diphenylmethylene-amino) phenyl) ethanone 7 with hydrogen chloride in tetrahydrofuran afforded 4-aminoacetophenone 1 (Scheme 1) [17, 18]. Reagents and conditions: (i) H2O /AuBr3 (ii) H2O / 2, 2, 2-trifluoroethanol (iii) H2O /cetyltrimethylammonim bromide/ isopropyl alcohol (iv) NaOH(aq) /MeOH,(v) tetrabutyl ammonium fluoride in tetrahydrofuran (vi) trifluoroacetic acid / dichloromethane(vii) hydrogen chloride/ tetrahydrofuran. Scheme 1. Synthesis of 4-aminoacetophenone Treatment of 2, 2, 2-trichloroethyl- 4-acetylphenylcarbamate 8 with indium and ammonium chloride in ethanol [19], or tert-butyl-4-acetylphenylcarbamate 9 [20], with water gave compound 1. Also, hydrolysis of 1-(4-(tert-butyldimethylsilylamino) phenyl)ethanone 10 with silica gel in ethanol/water [21], or 1-(4-(triethylsilylamino) phenyl) ethanone 11 with water afforded compound 1[22] (Scheme 2). Acid catalyzed hydrolysis of 1-(4-aminophenyl)-1-methoxyethanol 12 with phosphate buffer in water or 4-(1,1-dimethoxyethyl) benzene-mine 13 with hydrogen chloride in water afforded the 4-amino-acetophenone 1[23] (Scheme 3). Tao, C.-Z. et al., [24] reported a catalytic method to synthesized 4-aminoacetophenones from the 1-(4-bromo(iodo) phenyl)ethanones 14 under mild conditions using 2,2,2-trifluoroacetamide was used as ammonia surrogate, thus stirring of 1-(4-bromo (iodo)phenyl)ethanones with 2,2,2-trifluoroacetamide in the presence of CuI/N,N'-dimethyl ethylenediamine as catalyst in methanol/ water achieved the 4-aminoacetophenone (Scheme 2). Furthermore, Thakur, K. G. et al., report the using of CuI/D- glucosamine as an efficient catalyst for synthesis of 4-aminoacetophenone 1, thus, cross-coupling reaction between 1-(4-bromo(iodo)-phenyl)ethanones 14 and aqueous ammonia in presence of CuI, D-glucosamine and potassium carbonate in a mixture of acetone/water afforded the 4- aminoacetophenone [25] (Scheme 2). 22 To Chemistry Journal Vol 7 (2020) ISSN: 2581-7507 https://purkh.com/index.php/tochem The cross-coupling reaction between 1-(4-bromo(iodo)phenyl)-ethanone 14 and aqueous ammonia was efficiently catalyzed by the sulfonato–Cu (salen) complex in water with high yields, thus Coupling of 1-(4-bromophenyl)ethanone 14 or 1-(4-iodophenyl) ethanone 14 with aqueous ammonia in water in the presence of sodium hydroxide and in the presence of N,N'-bis(5- sulfonatosalicylidene)-1,2-diaminoethane]-copper disodium salt as acatalyst afforded the aminoacetophenone 1 [26] (Scheme 2). The copper(I) bromide/1-(5, 6, 7, 8- tetrahydroquinolin-8-yl)-2-methylpropan-1-one (CuBr-L3) combination catalyzed the cross- coupling reactions between 1-(4-bromo(iodo)phenyl)ethanone 14 and aqueous ammonia in dimethylsulfoxide in the presence of potassium phosphate with high yields to produce compound 1 at room temperature or under mild conditions [27]. Furthermore coupling of 4- iodoacetophenone 14 with tetramethylstannane and carbon monoxide in presence of tris-(o-tolyl) phosphine and tris(dibenzylideneacetone)dipalladium (0) in dimethylsulfoxide gave 1[28] (Scheme 2). H Cl N Cl O O Cl H N O CH3 O O CH H3C 3 O 8 CH3 H3C O 9 H C X i 3 H C ii H CH3 3 O N Si CH3 CH 14 vi,vii,viii,ixor.x H C 3 iii 3 H3C 10 v O H3CO NH2 NH 2 H3C H3C 1 ii CH3 OCH3 H O N CH 13 Si 3 iv H C HO H3C 3 NH2 11 H3C OCH3 12 Reagents and conditions: (i) indium, ammonium chloride in ethanol (ii) H2O (iii), silica gel EtOH/H2O (iv) H2O / phosphate buffer (v) H2O /HCl (vi) a-NH2COCF3.CuI, b-CH3OH/H2O, (vii) a-(2R,3S,4R,5S)- 3-amino-6-(hydroxymethyl)-tetrahydro-2H-pyran-2,4,5-triol,CuI, K2CO3/CH3COCH3, H2O,(viii) N,N'- bis(5-sulfonato-salicylidene-1,2-diaminoethane]copper disodium salt, ammonia, sodium hydroxide / H2O (ix) copper(I) bromide/1-(5,6,7,8-tetrahydroquinolin-8-yl-2-methylpropan-1-one, ammonia, K3PO4 / H2O/dimethyl sulfoxide (x) tetramethylstannane/carbomonoxide. Scheme 2. Synthesis of 4-aminoacetophenone. Reduction of 1-(4-nitrophenyl)ethanone 15 with hydrogen in methanol [29], ethanol [30], di sodium ethylenediamine tetra acetic acid and iron(II) sulfate/ water [31], NiRh3 in ethylacetate [32], ethylacetate [33], tetrahydrofuran [34], afforded the 4-aminoacetophenone. Furthermore, 4- aminoacetophenone 1 was prepared via reduction of 1-(4-nitrophenyl)ethanone 15 with sodium tetrahydroborate/tin (ll) chloride in ethanol, [35] hydrazine hydrate in ethanol [36], or tris(triphenyl- phosphine)-ruthenium(II) chloride, potassium hydroxide and zinc in 1,4-dioxane [37] (Scheme 3). Carole Guyon et al., [38] reported that reduction of 1-(4-nitrophenyl)ethanone 15 by hypophosphites catalyzed by Pd/C under biphasic 2-MeTHF/water solvent mixture afforded 4- aminoacetophenone 1 in addition to 4-ethylaniline 16 as a co-product [38] (Scheme 3). Furthermore, hydrogenation of 4-nitroacetophenone (4-NAP) 15 and 4-aminoacetophenone (4- AAP) 1 was examined over rhodium/silica catalysts. The reactions were carried out using isopropanol as a solvent under arrange of temperatures (303–333 K) and pressures (1–5 barg). It was observed that 1-(4-nitrophenyl)ethanone 15 underwent rapid hydrogenation of the NO2 23 To Chemistry Journal Vol 7 (2020) ISSN: 2581-7507 https://purkh.com/index.php/tochem group to form 1-(4-aminophenyl)-ethanone 1, followed by hydrogenation of the carbonyl group to give 1-(4-aminophenyl)ethanol 16, before ring saturation to give 1-(4-aminocyclohexyl)ethanol 17 and 4-ethylbenzenamine 18. Under selected conditions high selectivity and yield to either 1- (4-aminophenyl)ethanone 1 (99%) or 1-(4-aminophenyl)-ethanol 16 (94%) was achievable [39] (Scheme 3). Reagents and conditions: (i) H2, methanol (ii) H2, ethanol (iii), H2, disodiumethylene- diaminetetraacetic acid/ FeSO4/H2O (iv) H2, NiRh3 / ethylacetate (v) H2 / ethylacetate (vi) H2 / tetrahydrofuran/ H2O (vii) sodium tetrahydroborate/tin (ll) chloride/ethanol (viii) hydrazine hydrate / ethanol (ix) tris(triphenyl-phosphine)-ruthenium(II) chloride, potassium hydoxide, zinc /1,4- dioxane (x) Pd/C, NaH2PO2.H2O, 2-MeTHF, H2O, sonication (xi) H2/ rhodium/silica/ isopropanol. Scheme 3. Synthesis of 4-aminoacetophenone. Treatment of 1-(4-azidophenyl)ethanone 20 with ammonium hydroxide [40], samarium diiodide in tetrahydrofuran [41], BnEt3N]2MoS4 in water/cetonitrile [42], MoO2[S2CNEt2]2 and phenylsilane in toluene [43] , sodium sulfide in methanol [44] , or ammonium formate and zinc in methanol [45], gave 4-aminoacetophenone 1(Scheme 4). Reaction of (E)-1-(4- aminophenyl)ethanone oxime 21 with toluene-4-sulfonic acid in neat [46], sodium periodate and silica gel in solid [47], perchloric acid, dihydrogen peroxide, potassium bromide and hexaammonium heptamolybdate tetrahydrate in water,[48] sulfuric acid in 1,4-dioxane and water [49], afforded 4-aminoacetophenone 1(Scheme 4).