Quinacetophenone: A simple precursor to privileged organic motifs

El-Sayed Ibrahim El-Desoky; Mohamed Ahmed Abozeid; Abdel-Rahman Hassan Abdel-Rahman

doi:10.1016/j.arabjc.2015.09.010

View/Download PDF

Buy Reprints

PDF

Translate this page into:

Review

12 (

); 3380-3405

doi:

10.1016/j.arabjc.2015.09.010

Quinacetophenone: A simple precursor to privileged organic motifs

El-Sayed Ibrahim El-Desoky, Mohamed Ahmed Abozeid^⁎, Abdel-Rahman Hassan Abdel-Rahman

Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt

⁎Corresponding author. Tel.: +20 1004385945; fax: +20 502246254. dr_abozeid_chem@hotmail.com (Mohamed Ahmed Abozeid) mabouzeid@mans.edu.eg (Mohamed Ahmed Abozeid)

Received: 2015-3-15, Accepted: 2015-9-25, Published: 2015-12-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

This review presents the chemistry of quinacetophenone and its utility as an easily accessible building block for the synthesis of various advantageous organic compounds. This versatile precursor can be easily synthesized via different synthetic methodologies such as Friedel–Crafts acetylation, Fries rearrangement and Hoesch reaction. Based upon its inherent chemical reactivity, the title compound has been utilized to construct various organic molecules such as chalcones, chromones, flavonoids, coumarins, quinones and azoles including various naturally and biologically active compounds.

Keywords

Hydroxyacetophenone

Chalcone

Chromone

Flavone

Chromanone

Coumarin

Show Related Articles from PubMed

1 Introduction

o-Hydroxyacetophenones have been utilized in diverse syntheses of flavonoids and alkaloids (Fougerousse et al., 2000; Ruchirawat and Mutarapat, 2001; Kim et al., 2002 ) in addition to the synthesis of potential heterocyclic molecules (Huang et al., 2005). Moreover, they are widely used in the synthesis of pharmaceutics, perfumes, flavors, fragrances, dyes, plastics, antioxidants, stabilizers, fungicides (Naeimi and Moradi, 2005). Interestingly, o-hydroxy acetophenone has been used in the synthesis of cobalt nanoparticles through the thermal decomposition of its complex with cobalt metal (Salavati-Niasari et al., 2009). Basically, o-hydroxy acetophenones family covers a lot of examples; however, the most important members involve phloroacetophenone (Aponte et al., 2008; Müller et al., 2010), resacetophenone (Kolla and Lee, 2011; Chee et al., 2011a) and quinacetophenone (El-Desoky et al., 2014), as well as visnaginone (El Telbani et al., 1998; El-Desoky and Al-Shihry, 2008) and kellinone (Schönberg et al., 1953; Keshk, 2004) which can be found in a plenty of synthetic methodologies toward potential organic molecules (Fig. 1).

Quinacetophenone (2,5-dihydroxyacetophenone) 1 represents an easily accessible o-hydroxyacetophenone derivative and it has also been used for the synthesis of different potential organic molecules such as chalcones, flavonoids, chromones, coumarins, quinones and psoralens (Witiak et al., 1988; Cushman et al., 1994; Ishizuka et al., 2002; Wellington et al., 2010 ). As shown in Fig. 2, different medicinally active compounds have been synthesized from this versatile synthetic precursor (Cushman et al., 1994; Gerlach et al., 2001; El-Desoky et al., 2013 ). Additionally, quinacetophenone 1 has been used to synthesize various potential synthetic precursors which have been utilized in the synthesis of novel and complex heterocyclic compounds (Abdel-Rahman et al., 2005; Ali et al., 2006; El-Desoky et al., 2014). Encouraged by the aforementioned utility of o-hydroxyacetophenones, this review presents advantages of quinacetophenone (2,5-dihydroxyacetophenone) 1 as a simple and available precursor to synthesize diverse and advantageous organic molecules.

Different medicinally active compounds derived from quinacetophenone 1.

2 Preparation methods

2.1

2.1 Friedel–Crafts acetylation

Acetylation can be achieved by treating hydroquinone with acid chloride or anhydride in the presence of a Lewis acid (Scheme 1). Rosenmund and Lohfert reported the synthesis of quinacetophenone 1 through the reaction of hydroquinone with acetyl chloride in the presence of aluminum chloride under thermal conditions (Rosenmund and Lohfert, 1928).

On the other hand, acetylation with acetic acid instead of acetyl chloride or acetic anhydride is an environmentally benign reaction in which water is the only by-product (Naeimi and Moradi, 2007). Quinacetophenone 1 was obtained by the reaction of hydroquinone with acetic acid in the presence of acidic agents such as borontrifluoride etherate (BF₃·OEt₂), ferric chloride (FeCl₃), zinc chloride (ZnCl₂) and alumina/methanesulfonic acid (Al₂O₃/CH₃SO₃H) (Naeimi and Moradi, 2005). For instance, Hashem and coworkers carried out the acetylation of hydroquinone with acetic acid in the presence of Al₂O₃/CH₃SO₃H in 85% yield (Sharghi and Kaboudin, 1998).

Zinc powder is used to promote the Friedel–Crafts acetylation of hydroquinone with acetyl chloride under microwave irradiation in solvent-free conditions affording quinacetophenone 1 in 70% yield. Zn powder can be reused up to six times after simple washing with diethyl ether and dilute HCl (Paul et al., 2003). Similarly, the acetylation of hydroquinone using acetic acid in the presence of BF₃·OEt₂ under microwave conditions gave compound 1 in excellent yield (Gerlach et al., 2001). Furthermore, the regioselective solvent-free ortho-acetylation of hydroquinone with acetic acid in the presence of FeCl₃ under microwave irradiation afforded compound 1 in high yield within short reaction time (Naeimi and Moradi, 2007).

2.2

2.2 Fries rearrangement

Heating hydroquinone diacetate 2 in the presence of Lewis acids leaded to the formation of quinacetophenone 1 (Scheme 2) (Amin and Shah, 1950; Chen et al., 2004; Qin et al., 2009 ). Recently, Boyer and coworkers reported the use of Al₂O₃/CH₃SO₃H as a Lewis acid in the synthesis of quinacetophenone 1 from hydroquinone diacetate 2 via Fries rearrangement in a very good yield (89%) (Boyer et al., 2000). Fries rearrangement may proceed via an intramolecular, intermolecular or partially intra- and intermolecular mechanisms. Crossover study showed multiple mechanistic pathways. Khanna and coworkers reported that the crossover Fries rearrangement of hydroquinone diacetate 2 in the presence of hydroquinone afforded quinacetophenone 1 via treatment with BF₃·OEt₂ in benzene (Khanna et al., 1992). Furthermore, the crossover rearrangement proceeded by the treatment of hydroquinone diacetate 2 with different phenols such as phenol, phloroglucinol, 1-naphthol and 2-naphthol (Thapliyal and Aggarwal, 2000).

A long reflux time and excess amount of a Lewis acid are needed in order to synthesize quinacetophenone 1 via Fries rearrangement of hydroquinone diacetate 2. Therefore, the development of new catalysts is required for promoting the rearrangement in a clean and regioselective manner. AlCl₃–ZnCl₂ mixture supported on silica gel is an efficient catalyst which promotes the rearrangement under microwave heating conditions giving compound 1 in (90%) yield (Moghaddam et al., 1999).

2.3

2.3 Hoesch reaction

Quinacetophenone was also prepared via Hoesch reaction of hydroquinone with acetonitrile in the presence of trifluoromethanesulfonic acid followed by hydrolysis of the reaction mixture (Booth and Noori, 1980).

2.4

2.4 From benzoquinone

Klinger and Kolvenbach reported the synthesis of quinacetophenone 1 via a photochemical reaction between benzoquinone and acetaldehyde in a fairly good yield as shown in Scheme 3 (Klinger and Kolvenbach, 1898). Additionally, Kraus and coworkers carried out the reaction of benzoquinone with in situ generated acetyl radical, from pyruvic acid through the reaction with ammonium persulphate, to give quinacetophenone 1 in excellent yield (Scheme 3) (Kraus and Melekhov, 1998).

On the other hand, the Diels–Alder adduct 3, resulted from the reaction between 2-acetyl-1,4-benzoquinone and cyclopentadiene, underwent a retro reaction at 120 °C affording quinacetophenone 1 (Scheme 3) (Cooper and Sammes, 1980). Moreover, the target compound 1 can be constructed by other methods such as hydroxylation of acetophenone (Lindemann and Romanoff, 1929; Doppler et al., 1979; Kloetzel et al., 1955; Bruce and Roshan-Ali, 1981; Gesson et al., 1983; Konieczny et al., 2005; Lamba et al., 2006 ).

3 Reactions

3.1

3.1 Hydroxyl moiety based reactions

3.1.1

3.1.1 Alkylation

The mono- or di-o-alkyl derivatives 4 were obtained when quinacetophenone 1 was allowed to react with different alkyl halides such as methyl iodide, ethyl iodide, propyl iodide and others under basic conditions (Fig. 3) (Buckle et al., 1979; Bruce and Roshan-Ali, 1981; Srimal and Kar, 1983; Sircar et al., 1983; Hellwinkel and Bohnet, 1987; Wymann et al., 1988; Eggler et al., 1990; DeShong et al., 1991; Erickson et al., 1992; Wissner et al., 1992; Arvanitis et al., 1996; Fisher et al., 1998; Cecchi et al., 1999; Lim et al., 2001; Ishizuka et al., 2002; Roma et al., 2003, 2007; Kiyama et al., 2003; Koskelainen et al., 2004; Mmutlane et al., 2004; Summa et al., 2004; Doble et al., 2005; Lal et al., 2010; Casellas et al., 2006; Dong et al., 2006; Mays et al., 2010; Zbancioc et al., 2014 ).

As shown in Scheme 4, the non-hydrogen bonded, less crowded hydroxyl group of quinacetophenone 1 can be methylated regioselectively by the reaction with Me₂CO₃ in the presence of potassium carbonate yielding 2-hydroxy-5-methoxyacetophenone 5 in moderate yield (Chen et al., 2004). Similarly, the same hydroxyl group of compound 1 can be capped as silyl ether by the reaction with tert-butyldimethylsilyl chloride (TBDMS-Cl) in the presence of 1H-imidazole in excellent yield (Scheme 4) (Aggarwal et al., 2005).

Moreover, the reaction of quinacetophenone 1 with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranose 7 via two different methods (Fischer and Koenigs–Knorr) yielded 2-hydroxy-5-O-(2,3,4,6-tetra-O-acetyl-β-D-2-galactopyranosyloxy)acetophenone 8. The deprotection of compound 8 was accomplished by sodium methoxide producing 2-hydroxy-5-(β-D-2-galactopyranosyloxy)acetophenone 9 (Scheme 5) (Konishi et al., 1983).

Quinacetophenone 1 could also be transformed into mono- or di-(tetrahydropyranyl) ethers 10 or 11 by reaction with 3,4-dihydro-2H-pyran in the presence of pyridinium p-toluenesulfonate (Fig. 4) (Fillaut et al., 2008; Cheng et al., 2008; Mutai et al., 2015 ). Furthermore, 2-hydroxy-5-perfluoroalkoxy acetophenone 12 was synthesized by the reaction of 1 with 1H, 1H, 2H, 2H-perfluoro-1-decane triflate under basic medium and it is a dye stabilizer having high quenching efficiency and stability in halogenated solvents. This dye stabilizer improved the dye fastness in hostile thermal and/or photooxidation conditions (Fig. 4) (Feng et al., 2004).

The reaction of quinacetophenone with allyl bromide in the presence of potassium carbonate afforded the corresponding O-Allylated derivative 13 in excellent yield. Under thermal reaction conditions, compound 13 underwent Claisen rearrangement yielding 3,6-dihydroxy-2-allylacetophenone 14 in good yield (Scheme 6) (Pillay et al., 2012).

3.1.2

3.1.2 Acylation

Quinacetophenone 1 can be acylated with different alkyl, cycloalkyl, aryl and heteroaryl acid chlorides in basic medium affording the corresponding diacylated products 15a–w (Fig. 5) (Russell and Clark, 1939; Erickson et al., 1992; Mitchell et al., 1995; Billich et al., 1999; Nussbaumer et al., 2002; Vasquez-Martinez et al., 2007; Jayashree et al., 2010 ). In addition, treatment of compound 1 with tert-butyl dicarbonate afforded diacylated derivative 15x (R = (CH₃)₃CO) in 82% yield (Jones et al., 2001). Similarly, Baker reported that the acetylation of 1 by using acetic anhydride and anhydrous sodium acetate afforded 2-hydroxy-5-acetoxyacetophenone 16 (Fig. 5) (Baker, 1934).

On the other hand, Candida Antarctica Lipase B (CAL-B) was found to be a highly active biocatalyst for the direct acylation of compound 1 with vinyl acetate and propanoate as acyl donors affording compounds 16, 17 and 18 (Fig. 5) (Nicolosi et al., 1993; Miyazawa et al., 2008). Additionally, Rajakumar and coworkers reported the synthesis of cyclophane diamide 20 by the reaction of quinacetophenone 1 with N,N′-(α,α′dichloroacetyl)-1,2-phenylenediamine 19 (Scheme 7) (Rajakumar et al., 2006).

3.2

3.2 Active methylene moiety based reactions

3.2.1

3.2.1 Mannich reaction

Agarwal and coworkers reported that quinacetophenone 1 underwent Mannich reaction with aniline and benzidine to produce the corresponding Mannich bases 21 and 22, respectively (Fig. 6) (Agarwal and Saxena, 1980).

3.2.2

3.2.2 Claisen–Schmidt reaction

2-Hydroxychalcones are considered as very economically precursors for construction of the highly medicinally active flavones and related motifs. Also, most of 2,5-dihydroxychalcone derivatives showed excellent antiinflammatory activity due to their potent inhibitory effects on the release of chemical mediators from inflammatory cells (Ko et al., 2003). These interesting motifs can be obtained by Claisen–Schmidt condensation of quinacetophenone 1 with a series of aromatic and heteroaryl aldehydes (Vyas and Shah, 1949; Bruce et al., 1953; Fujise et al., 1954; Hsieh et al., 1998; Ko et al., 2003; Nam et al., 2003; Won et al., 2005 ; Moorthy et al., 2006; Singh et al., 2010; Avupati et al., 2012; Kupcewicz et al., 2014; Ravichandran et al., 2014 ). The condensation of protected quinacetophenone 1 with aldehydes afforded various hydroxyl protected chalcones 23(1–29) which gave the corresponding dihydroxychalcones 24(1–29) by deprotection in the presence of p-toluenesulfonic acid (Scheme 8). The produced chalcones 24(1–29) showed excellent antiinflammatory and antitumor activities (Hsieh et al., 1998; Ko et al., 2003; Nam et al., 2003 ).

As shown in Scheme 9, other protecting groups can be utilized instead of tetrahydropyranyl groups during the formation of chalcones. The reaction of the benzyl protected quinacetophenone 25a with the benzyl protected salicaldehyde 26 in 40% aqueous solution of KOH afforded the corresponding protected hydroxychalcone 27. Then, the deprotection of the benzyl ether 27 was accomplished via treatment with boron trichloride (BCl₃) to afford the targeted hydroxychalcone 28 which showed high in vitro inhibitory activity of β-secretase (a molecular target for therapeutic intervention in Alzheimer’s disease) (Ma et al., 2011). Similarly, by using quinacetophenone protected as methyl ether 25b, pyrrole containing chalcone 30 was synthesized in moderate yield (Rane et al., 2013).

On the other hand, the reaction of 4-nitrobenzaldehyde, 9-anthraldehyde or acetaldehyde with quinacetophenone 1 in basic medium failed to give the corresponding chalcones. Alternatively, these products were obtained by condensation under acidic medium (Russell and Happoldt, 1942; Bruce et al., 1953; Nam et al., 2003 ). Additionally, Won and coworkers reported that 3,5-di-tert-butyl-4-hydroxystyrylhydroquinone 32 was formed in one-pot synthesis by treatment of 1 and 3,5-di-tert-butyl-4-hydroxybenzaldehyde 31 by ultrasonic agitation on basic alumina (Scheme 10) (Won et al., 2005).

Konishi and coworkers reported the synthesis of 4-(β-D-2-galactopyranosyloxy)-2-(3′-hydroxy-4′-methoxycinnamoyl)phenol 33 which was reduced with hydrogen in the presence of Pd–C (10%) catalyst yielding the corresponding dihydrochalcone 34 (Scheme 11) (Konishi et al., 1983).

3.2.3

3.2.3 Synthesis of α,γ-diketo acid (DKA)

α,γ-Diketo acids (DKA) were discovered as selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The diketo acid moiety proved to be essential for this activity, while substitution on the γ-position was necessary for selectivity and potency (Summa et al., 2004). As shown in Scheme 12, O-alkylation of compound 1 by using two different alkylating agents 2-cyanobenzyl bromide and δ-bromovaleronitrile in the presence of Cs₂CO₃, yielded 2-((3-acetyl-4-(3-cyanopropoxy)phenoxy) methyl)benzonitrile 35. Compound 35 was reacted with diethyloxalate in NaOEt to give C-benzoylpyruvic acid derivative 36 (Scheme 12) via Claisen condensation (Summa et al., 2004).

3.2.4

3.2.4 Synthesis of β-diketone

O-benzylation of 2-hydroxy-5-methoxyacetophenone 37 using 2-methoxycarbonyl benzyl bromide 38 afforded the expected 2-benzyloxy-5-methoxyacetophenone 39 which was cyclized via Claisen condensation to give 2-methoxydibenzo[b,g]oxonine-11,13(6H,12H)-dione 40 (Scheme 13) (Hellwinkel and Bohnet, 1987).

3.2.5

3.2.5 Synthesis of β-hydroxy carbonyl compound

The reaction of 1 with acetone in the presence of lithium diisopropylamide gave 1-(2,5-dihydroxyphenyl)-1-oxo-methylbutane-3-ol 41 (Fig. 7) (Banerji and Goomer, 1984).

3.2.6

3.2.6 Bromination

2-Bromo-hydroxyacetophenones are important intermediates in the synthesis of various biologically active compounds in addition to their use in the manufacture of simulated photographic quality print, stabilizers of hydrogen peroxide in paper industry and other applications. Selective bromination of quinacetophenone 1 at the active methylene moiety was accomplished via different routes (Scheme 14). The most efficient methodology involves the bromination of quinacetophenone 1 using bromine in the presence of AlCl₃ and Montmorillonite K10 (Uchil and Joshi, 2003). Additionally, 2,5 dihydroxyphenacyl bromide 42 was synthesized by the refluxing of 1 with CuBr via ultrasound-assisted bromination in heterogeneous catalysis as shown in Scheme 14 (Zbancioc et al., 2010). Finally, the same product 42 was obtained by the microwave irradiation of quinacetophenone 1 in the presence of urea–hydrogen peroxide complex and sodium bromide over silica gel–acetic acid (Paul et al., 2005).

3.3

3.3 Carbonyl moiety based reactions

3.3.1

3.3.1 Acetal formation

The reaction of quinacetophenone 1 with ethylene glycol in the presence of p-toluenesulfonic acid afforded 2-(2-methyl-1,3-dioxolan-2-yl) benzene-1,4-diol 43 in excellent yield (Scheme 15) (Beddoes et al., 1981).

3.3.2

3.3.2 Horner–Emmons–Wadsworth reaction

α,β-Unsaturated esters are considered as a good synthons for different heterocyclic compounds. The reaction of dibenzyl ether 25a with triethyl phosphonoacetate via Horner–Emmons–Wadsworth reaction (HWE reaction) in the presence of potassium tert-butoxide furnished predominantly ester E-44 (E:Z = 8:1) in excellent yield (Scheme 16) (DeShong et al., 1991).

3.3.3

3.3.3 Condensation reactions

The condensation of quinacetophenone 1 with hydroxylamine hydrochloride afforded the corresponding oxime 45 in excellent yield. Moreover, different Schiff bases 46–48 were obtained by the reaction of 1 with aryl and heteroaryl amines. Also, the treatment of 1 with hydrazine monohydrate as well as different hydrazines furnished the corresponding hydrazones 49–54 (Horii, 1937; Veibel and Schmidt, 1948; Verma and Verma, 1983; Manrao et al., 1984; Petrov et al., 2002; Mandlik and Aswar, 2003; Lyssikatos et al., 2007; Nair and Shamla, 2009; Sakamoto and Okuyama, 2014a, 2014b ). In addition, the condensation of compound 1 with semicarbazide hydrochloride afforded the corresponding semicarbazone 55 in 84% yield (Fig. 8) (Petrov et al., 2006).

3.3.4

3.3.4 Synthesis of oxadiazinanone derivative

Recently, 2-(2,5-dihydroxyphenyl)-2-methyl-1,3,4-oxadiazinan-5-one 57 was synthesized by the reaction of quinacetophenone 1 and cyanoacetic acid hydrazide 56 in acetic acid (Scheme 17) (Parveen et al., 2013).

3.3.5

3.3.5 Reduction

Depending upon the nature of the reductant, different products 58–60 were obtained by the reduction of quinacetophenone 1. Firstly, ethyl hydroquinone 58 was obtained through the reduction of carbonyl group via different methods (A: Clemmensen reduction; B: Wolff–Kishner reduction; C: H₂/Pd; D: H₂/copper(II) chromite) (Verheggen et al., 2007; Wu et al., 1987; Kneppe and Schneider, 1983; Vandenberghe and Willems, 1965 ). Moreover, α-phenylethanol 59 was produced by performing the reduction using HCl/sodium cyanoborohydride (Miyamura et al., 2008). On the other hand, the reductive dimerization of 1 was accomplished in the presence of NaOH/sodium amalgam to give diphenylbutan-2,3-diol derivative 60 (Scheme 18) (Gie, 1945).

3.4

3.4 Methyl ketone moiety based reactions

3.4.1

3.4.1 Synthesis of azoles

The reaction of quinacetophenone 1 with ethyl hydrazinecarboxylate followed by the treatment with thionyl chloride afforded 4-(2,5-dihydroxyphenyl)-1,2,3-thiadiazole 61 in moderate yield (Petrov et al., 2002). Similarly, selenadiazole derivative 62 was synthesized via the conversion of quinacetophenone 1 into the corresponding diacetylated semicarbazone followed by the reaction with SeO₂ and hydrolysis (Petrov et al., 2006). Sanchez-Viesca and coworkers reported the synthesis of 2-methyl-4(2,5-dihydroxyphenyl)thiazole 63 through the bromination of quinacetophenone 1 and subsequent reaction with thioacetamide (Scheme 19) (Sanchez-Viesca et al., 2003).

Pyrazole 64 was identified as a specific inhibitor of N-acetyltransferase enzyme (NAT) which had been implicated as a potential antitubercular target. This pyrazole 64 was synthesized from 2-hydroxy-5-methoxyacetophenone 37 via a Claisen-type reaction followed by subsequent condensation with hydrazine (Scheme 20). Guided by in silico molecular docking studies, other potent antitubercular pyrazoles 65, 66 and 67 were designed, and synthesized via similar manner (Scheme 20) (Fullam et al., 2013).

3.4.2

3.4.2 Synthesis of indole heterocycle

O-Methylation of quinacetophenone 1 followed by the reaction with phenylhydrazine, subsequent Fischer indolization and finally demethylation yielded indole derivative 68 (Scheme 21) (Sharma et al., 1983).

3.5

3.5 Hydroxyacetyl moiety based reactions

3.5.1

3.5.1 Synthesis of chromones

Most of chromones possess a broad range of biological activities, such as antimycobacterial, antifungal, anticancer, antimicrobial and others. These derivatives are also important intermediates in the manufacture of agrochemicals and pharmaceuticals (Tu et al., 2013). Acylation of compound 1 followed by Baker–Venkataraman rearrangement afforded 1,3-diketones 69a–g. Cyclization of the diketones 69a–g in acidic medium followed by hydrolysis afforded 6-hydroxychromones 70a–g (Scheme 22) (Erickson et al., 1992; Billich et al., 1999; Nussbaumer et al., 2002 ).

Also, chromones 71 and 72 were synthesized by the reaction of quinacetophenone 1 with acetic anhydride or diethyl oxalate under basic conditions (Scheme 23) (Mujica-Fernaud et al., 2004; Desai and Mavani, 1947).

Park and coworkers utilized quinacetophenone 1 as a starting materials to synthesize 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives with selective anti-HCV activity (Park et al., 2011). Oxidation of 1 with PhI(OAc)₂ in MeOH furnished the corresponding 6-methoxy derivative in 45% yield followed by protection with benzyl and acetyl groups to provide the intermediate 73. Intramolecular Claisen condensation of 73 in the presence of tert-BuOK resulted in the construction of the chromone 74. Oxidation of the alkyl moiety yielded the corresponding aldehyde, which underwent reduction followed by bromination to give 2-bromomethylchromone derivative 75. Compound 75 was treated with different arylmethylamines followed by deprotection to give the desired 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives 76 in 40–80% yield (Scheme 24). The latter synthesized 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives 76 showed selective anti-HCV effect with no cytotoxicity up to 100 μM (Park et al., 2011).

On the other hand, the potent and selective monoamine oxidase B (MAO-B) inhibitors are crucial for the therapy of neurodegenerative disorders such as Parkinson’s disease. Based on the pharmacophoric chromone, a series of chromone-3-(carboxaldehyde, carboxylic acid and carboxylic ester) were synthesized from the versatile precursor quinacetophenone 1 (Scheme 25). The compounds 79, 80 and 81 are potent and selective MAO-B inhibitors [IC₅₀ = 0.0028, 0.004, 0.0057 μM] (Legoabe et al., 2012).

Via Vilsmeier Haack reaction, the treatment of quinacetophenone 1 with POCl₃/DMF afforded 6-hydroxy-4H-4-oxo[l]benzopyran-3-carboxaldehyde 82 which is very powerful synthon for various heterocyclic compounds such as azoles, azepine, pyridine and pyrimidines (Scheme 26) (Abdel-Rahman et al., 2005; Qin et al., 2009; Tu et al., 2013). Additionally, the treatment of quinacetophenone 1 with triethyl orthoformate and perchloric acid (70%) followed by aqueous hydrolysis of the intermediate perchlorate salt afforded the corresponding 6-hydroxy-4H-4-oxo[1]benzopyran 83 in moderate yield.

3.5.2

3.5.2 Synthesis of chromanones

Refluxing of quinacetophenone 1 with aliphatic aldehydes and ketones namely acetone, butanone, cyclopentanone, cyclohexanone, cycloheptanone, tert-butyl-4-oxopiperidine-1-carboxylate, 1-benzyl-4-piperidine, 4-oxo-butyric acid tert-butyl ester, sulcatone, geranylacetone, nerylacetone, farnesylacetone, phytone (hexahydrofarnesylacetone) and 14-hydroxy-tetradecan-2-one in the presence of basic catalyst such as pyrrolidine and piperidine leaded to the synthesis of the corresponding chromanones 84a–q in excellent yields (Scheme 27) (Yamato et al., 1981; Kabbe and Widdig, 1982; Mizuguchi et al., 1993; Pearce et al., 1994; Cascaval et al., 1998; Le et al., 2008; Letourneau et al., 2005; Tripathi et al., 2009; Lingam et al., 2010; Coowar et al., 2010; Kallan et al., 2011; Becknell et al., 2012; Dandu et al., 2012; El-Desoky et al., 2013 ). Compared to other secondary amines, pyrrolidine proved to be the best catalyst for the synthesis of chromanone derivatives 84a–q from quinacetophenone 1. In contrast, chromanone derivatives 84a–q could not be synthesized in the presence of sodium hydroxide or tertiary amines catalysts (Yamato et al., 1981; Kabbe and Widdig, 1982; Mizuguchi et al., 1993; Pearce et al., 1994; Cascaval et al., 1998; Gerlach et al., 2001; Le et al., 2008; Tripathi et al., 2009; Lingam et al., 2010; Coowar et al., 2010 ). In 2009, microwave was exploited for initiating the reaction leading to excellent yields of compounds 84a,b,k,l (Tripathi et al., 2009; Lingam et al., 2010).

The reaction mechanism for the formation of 2,2-dialkyl or spirocycloalkyl (or heterocycloalkyl)chromanones 84a–q was proposed by Kabbe and Widdig as shown in Scheme 28 (Kabbe and Widdig, 1982). In the first step, the base (pyrrolidine) reacts with the aldehyde or ketone to form alkylidene ammonium ion 85 or enamine 86 forms. Either of them reacts with quinacetophenone 1 by the effect of base via Michael addition to yield the Michael adduct 87. Finally, the latter compound 87 may either undergo nucleophilic displacement of pyrrolidine by the phenolic moiety affording the target 4-chromanone derivatives 84a–q or eliminate pyrrolidine to give the enone 88.

Unfortunately, 4-(1-pyrrolidinyl)chromenes 89 were formed during these reactions (usually less than 15%) and this is explained as shown in Scheme 29 (Kabbe and Widdig, 1982).

3.5.3

3.5.3 Synthesis of flavonoids

Flavonoids are a class of natural products that are known to have antioxidant activity as well as a wide range of other pharmacological properties. One of the classical methods for the preparation of their γ-pyrone structure is via the Baker–Venkataraman rearrangement (Chee et al., 2011b). Acylation of quinacetophenone 1 with benzoic, anisic and trimethylgallic anhydrides 90a–c in the presence of sodium salt of the corresponding acid followed by Baker–Venkataraman rearrangement and cyclization afforded the corresponding flavones 91a–c (Scheme 30) (Chadha and Venkataraman, 1933).

By heating quinacetophenone 1 with excess benzoyl chloride in wet K₂CO₃/acetone, the corresponding flavone 92 was obtained in 51% yield in addition to 3-benzoylflavone 93 in 23% yield. The proposed mechanism for the formation of flavone 92 and 3-benzoylflavone 93 is shown in Scheme 31 (Chee et al., 2011b).

The generation of lithium enolate from acetyl group of quinacetophenone 1 was achieved by using lithium bis(trimethylsilyl)amide (LiHMDS) and then, treatment of these lithium polyanions with acid chlorides afforded the diketones 100a,b in quantitative yields. Cyclization of these diketones 100a,b in the presence of H₂SO₄ and AcOH afforded the flavones 101a,b (Scheme 32) (Cushman et al., 1994). Similarly, flavone 102 was prepared by using Li(OH)₂ as a base under inert conditions (Scheme 32) (Carola et al., 2004).

The reaction of compound 1 with 5-aldehydosalicylic acid 103/orthoformic acid in the presence of perchloric acid (70%) followed by hydrolysis afforded the corresponding flavone 104 (Scheme 33) (Oganesyan et al., 1989).

Additionally, quinacetophenone 1 was utilized in the synthesis of isoflavones 108a–d via the enaminone intermediate 105. After the one pot-two step ring closure and iodination via addition of I₂ in MeOH, the key precursor 3-iodochromone 106 was produced in good yield. Using a green approach for the Suzuki reaction, 3-iodochromone 106 was coupled with phenylboronic acids 107a–d in the presence of Pd(OAc)₂ along with poly(ethylene glycol) 10,000 (PEG 10,000) as the ligand to give isoflavones (3-phenylchromen-4-ones) 108a–d efficiently (Scheme 34) (Biegasiewicz et al., 2014).

The reaction of quinacetophenone 1 with aromatic aldehydes in ethylorthoformate in the presence of perchloric acid (70%) gave the corresponding 4-ethoxyflavylium perchlorate derivatives 109a–c (Scheme 35) (Oganesyan et al., 1989; Sato et al., 1999).

On the other hand, the recent studies have demonstrated that silybin exerts cytotoxic activity against cancer cell lines; however the main drawback is that silybin manifests poor anti-proliferative activity against MCF-7 cell line because of its low bioavailability and poor water solubility. As an attempt to circumvent these issues, silybin analogues 115 and 116 were constructed from quinacetophenone 1 as shown in Scheme 36. After evaluation of the anti-proliferative activity against SKBR3 (estrogen receptor negative, HER2 over-expressing breast cancer cells) and MCF-7 (estrogen receptor positive breast cancer cells) cell lines, silybin analogues 115 and 116 exhibited improved anti-proliferative activity compared to the natural silybin (Scheme 36) (Zhao et al., 2011a, 2011b).

3.6

3.6 Electrophilic substitution reactions

3.6.1

3.6.1 Nitration

The nitration of quinacetophenone 1 with a mixture of HNO₃ and CH₃CO₂H afforded 2,5-dihydroxy-3-nitroacetophenone 117, while only 2,5-dihydroxy-2,6-dinitro acetophenone 118 was generated by using conc. HNO₃ (Scheme 37) (Desai et al., 1954).

3.6.2

3.6.2 Halogenation

The electrophilic substitution of quinacetophenone 1 by the reaction with bromine yielded the mono and dibromo derivatives 119 and 120 (Desai et al., 1954). Also, free radical electrophilic substitution reaction of 1 with N-chlorosuccinimide (NCS) under inert atmosphere afforded 1-(3-chloro-2,5-dihydroxy)phenylethanone 121 (Scheme 38) (Baker et al., 2011).

3.7

3.7 Miscellaneous reactions

3.7.1

3.7.1 Synthesis of phenazine derivative

A facile synthesis of acetylphenazine derivative 123 was accomplished via refluxing of equimolar amounts of 2,5-dihydroxyacetophenone 1 and benzofuroxan 122 in the presence of molecular sieves 4 Å (Scheme 39) (Takabatake et al., 2000).

3.7.2

3.7.2 Synthesis of quinone derivatives

Quinacetophenone 1 can be oxidized into the corresponding 2-acetyl-1,4-benzoquinone 124 in a very good yield by a wide variety of oxidizing agents such as silver oxide, manganese dioxide, manganese dioxide impregnated with nitric acid, Au clusters immobilized on a polystyrene based polymer/O₂ and silica gel supported heterogeneous ceric ammonium nitrate (CAN) (Fig. 9) (Cassis and Valderrama, 1983; Brimble et al., 2004; Ali et al., 2006; Miyamura et al., 2008 ).

Additionally, Niedermeyer and coworkers reported a novel procedure for the oxidation of quinacetophenone 1 into 2-acetylbenzoquinone 124 by using laccase, copper containing phenol oxidases, catalyzed reactions in the presence of oxygen (Niedermeyer et al., 2005). Quinone 124 is well known precursor for the synthesis of different biologically active molecules (Ali et al., 2006).

On the other hand, the natural product marticin that was produced by Fusarium solani and Fusarium martii, possesses antibacterial activity against Staphylococcus aureus (128 μg/mL) and Staphylococcus pyogenes (128 μg/mL). In 2012, Pillay and coworkers reported a methodology to construct the quinone core structure 131 of marticin starting from quinacetophenone 1 (Scheme 40) (Mmutlane et al., 2004; Pillay et al., 2012).

By going to extended quinone structure, the reaction of 1 with phthalic anhydride in the presence of H₂SO₄ and H₃BO₃ afforded 2-acetyl-1,4-dihydroxyanthracene-9,10-dione 132 (Scheme 41) (Willstaedt and Michaelis, 1938).

3.7.3

3.7.3 Synthesis of benzofurans

The benzofurans functionalized with hydroxyl and acetyl groups are not only the core structures found in a large number of biologically important natural products, but also the vital precursors for several naturally occurring furoflavonoids. In addition, benzofuran and dihydrobenzofuran derivatives and their dimers in isolated or rigid conformations are key structural units found in large number of medicinal plants (Dixit et al., 2006).

Numerous synthetic methodologies are available in the literature for the construction of benzofuran ring system due to its wide-ranging applications. Two isomeric benzofurans, 6-acetyl-5-hydroxybenzofuran 134 and 4-acetyl-5-hydroxybenzofuran 135 were synthesized in good yield from commercially available quinacetophenone 1 through α-phenoxyacetaldehyde diethylacetal intermediate 133. Heating benzofuran derivatives 134 and 135 in the presence of amberlyst 15 afforded the benzofuryl benzofuran derivatives 136 and 137, respectively in good yield (Scheme 42) (Dixit et al., 2006).

Also, the reaction of 1 with p-substituted phenacyl bromide 138 in the presence of K₂CO₃ furnished the 2-benzoyl-3-methylbenzofuran derivative 139 in moderate yield (Scheme 43) (Belanger et al., 1985). Yamaguchi and coworkers reported the synthesis of 2-vinyl substituted dihydrobenzofuran derivatives 141 and 142 by the reaction of quinacetophenone 1 with 1,4-dibromo-2-methyl-2-butane 140 in the presence of sodium hydride (Scheme 43) (Yamaguchi et al., 1986).

Additionally, a series of 2-benzylidene-benzo[b]furan-3-ones (aurones) 147 were designed depending upon docking studies to be screened as inhibitors for preadipocyte proliferation and differentiation. The synthetic strategy depends upon the mono methoxymethylation of 1 and subsequent formation of the corresponding chalcones 144. Then, aurones 145 were obtained via the oxidative cyclization methodology using mercury acetate in pyridine as Z-geometry. Finally, the deprotection of the MOM group was followed by acylation with in situ prepared fatty acid chloride affording the corresponding aurone esters 147 (Scheme 44). After evaluating the activity of the synthesized aurones 147, different compounds could efficiently inhibit preadipocyte proliferation and adipogenesis in comparison with Oleoyl Formononetin (OF) in addition to enhancement of glucose consumption in the cells (Zhao et al., 2011a, 2011b).

3.7.4

3.7.4 Synthesis of coumarins

There are many synthetic routes to construct coumarins including Pechmann, Perkin, Knoevenagel, Reformatsky and Wittig reactions (De and Gibbs, 2005). As shown in Scheme 45, the reaction of quinacetophenone 1 with phenylacetyl chloride in the presence of potassium carbonate furnished 6-hydroxy-4-methyl-3-phenylcoumarin 148 (Neelakantan et al., 1982). As also depicted in Scheme 45, Brubaker and coworkers reported that the reaction between quinacetophenone 1 and [(ethoxycarbonyl)-methylene]triphenylphosphone (Ph₃P = CHCOOC₂H₅) afforded 6-hydroxy-4-methyl-2H-1-benzopyran-2-one 149 (Brubaker et al., 1986).

In 2002, Bandgar and coworkers reported that under microwave irradiation a mixture of 1 and Meldrum’s acid in the presence of lithium perchlorate afforded 6-hydroxycoumarin-3-carboxylic acid 150 in a very good yield (Scheme 46) (Bandgar et al., 2002). Additionally, Salama and coworkers developed a simple, mild and efficient protocol for the one-pot synthesis of coumarin-3-carbonitriles 151 via a typical Knoevenagel condensation of 1 and malononitrile in 86% yield using SiCl₄ as dehydrating agent (Scheme 46) (Salama et al., 2012).

4 Conclusion

Quinacetophenone is one of the most important o-hydroxyacetophenones which represents an useful precursor in both organic and medicinal chemistry. This versatile precursor can be easily synthesized via different methods such as Friedel–Crafts acetylation and Fries rearrangement. Based upon its chemical moieties, various chemical transformations have been designed. As a result, quinacetophenone has been used for the synthesis of various naturally and biologically active compounds.

References

Abdel-Rahman A.H., Hammouda M.A.A., El-Desoky S.I., . Synthesis of some new azole, azepine, pyridine, and pyrimidine derivatives using 6-hydroxy-4H-4-oxo[1]-benzopyran-3-carboxaldehyde as a versatile starting material. Heteroat. Chem.. 2005;16:20-27.
[Google Scholar]
Agarwal S.K., Saxena R.C.J., . Synthesis, characterization and screening of antibacterial activity of some new Mannich bases. Indian Chem. Soc.. 1980;57:1240-1241.
[Google Scholar]
Aggarwal R., Giles R.G.F., Green I.R., Oosthuizen F.J., Taylor C.P., . Syntheses in enantiopure form of four diastereoisomeric naphthopyranquinones derived from aphid insect pigments. Org. Biomol. Chem.. 2005;3:263-273.
[Google Scholar]
Ali M.H., Niedbalski M., Bohnert G., Bryant D., . Silica-gel-supported ceric ammonium nitrate (CAN). A simple and efficient solid-supported reagent for oxidation of oxygenated aromatic compounds to quinones. Synth. Commun.. 2006;36:1751-1759.
[Google Scholar]
Amin G.C., Shah N.M.J., . Fries migration. V. Fries migration of 4-methoxyquinol esters and 4-benzoxyquinol acetate. Indian Chem. Soc.. 1950;27:531-534.
[Google Scholar]
Aponte J.C., Verástegui M., Málaga E., Zimic M., Quiliano M., Vaisberg A.J., Gilman R.H., Hammond G.B., . Synthesis, cytotoxicity, and anti-Trypanosoma cruzi activity of new chalcones. J. Med. Chem.. 2008;51:6230-6234.
[Google Scholar]
Arvanitis A.G., Scholfield E.L., Grigoriadis D., Heytler P.G., Bowdle J., Chorvat R.J., . Alkylbenzyl ethers of hydroquinones as monoamine oxidase B inhibitors. Bioorg. Med. Chem. Lett.. 1996;6:115-120.
[Google Scholar]
Avupati V.R., Yejella R.P., Akula A., Guntuku G.S., Doddi B.R., Vutla V.R., Anagani S.R., Adimulam L.S., Vyricharla A.K., . Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents. Bioorg. Med. Chem. Lett.. 2012;22:6442-6450.
[Google Scholar]
Baker Jr., J.R., Huang, B.M., Thomas, T.P., 2011. Prodrug Complexes and Related Methods of Use. Patent WO 2011002852.
Baker W., . Attempts to synthesize 5,6-dihydroxyflavone (primetin) J. Chem. Soc. 1934:1953-1954.
[Google Scholar]
Bandgar B.P., Uppalla L.S., Sadavarte V.S., . Lithium perchlorate and lithium bromide catalyzed solvent free one pot rapid synthesis of 3-carboxycoumarins under microwave irradiation. J. Chem. Res., Synop. 2002:40-41.
[Google Scholar]
Banerji A., Goomer N.C., . Synthesis of naturally occurring 6-oxygenated-2,2-dimethylchromenes. Indian J. Chem. Sect. B. 1984;23:885-886.
[Google Scholar]
Becknell N.C., Dandu R.R., Lyons J.A., Aimone L.D., Raddatz R., Hudkins R.L., . Synthesis and evaluation of 4-alkoxy-[1′-cyclobutyl-spiro(3,4-dihydrobenzopyran-2,4′-piperidine)] analogues as histamine-3 receptor antagonists. Bioorg. Med. Chem. Lett.. 2012;22:186-189.
[Google Scholar]
Beddoes R.L., Bruce J.M., Finch H., Heelam L.M.J., Hunt I.D., Mills O.S., . Benzoquinones and related compounds. Part 4. Thermolysis of the Diels-Alder adduct of 2-acetyl-5,6-dichloro-1,4-benzoquinone and cyclopentadiene: evidence for a partial retro-diene reaction. J. Chem. Soc. Perkin Trans.. 1981;1:2670-2676.
[Google Scholar]
Belanger, P.C., Scheigetz, J., Rokach, J., 1985. Benzofuran and Benzothiophene Derivatives and Their Use in Inhibiting Mammalian Leukotriene Biosynthesis. Patent EP 165810.
Biegasiewicz K.F., Gordon J.S. IV, Rodriguez D.A., Priefer R., . Development of a general approach to the synthesis of a library of isoflavonoid derivatives. Tetrahedron Lett.. 2014;55:5210-5212.
[Google Scholar]
Billich, A., Nussbaumer, P., Schreiner, E., Schuster, I., 1999. Preparation of Chromanone and Thiochromanone Derivatives as Steroid Sulfatase Inhibitors. Patent WO 9952890.
Booth B.L., Noori G.F.M., . The chemistry of nitrilium salts. Part 1. Acylation of phenols and phenol ethers with nitriles and trifluoromethanesulfonic acid. J. Chem. Soc. Perkin Trans.. 1980;1:2894-2900.
[Google Scholar]
Boyer J.L., Krum J.E., Myers M.C., Fazal A.N., Wigal C.T., . Synthetic utility and mechanistic implications of the Fries rearrangement of hydroquinone diesters in boron trifluoride complexes. J. Org. Chem.. 2000;65:4712-4714.
[Google Scholar]
Brimble M.A., Burgess C., Halim R., Petersson M., Ray J., . Synthesis of pyrrolo[3,2-b]benzofurans and pyrrolo[3,2-b]naphthofurans via addition of a silyloxypyrrole to activated quinones. Tetrahedron. 2004;60:5751-5758.
[Google Scholar]
Brubaker A.N., De R.J., Whitmer W.L., . Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2-ones. J. Med. Chem.. 1986;29:1094-1099.
[Google Scholar]
Bruce D.B., Sorrie A.J.S., Thomson R.H., . Reactions in fused aluminum chloride–sodium chloride. J. Chem. Soc. 1953:2403-2406.
[Google Scholar]
Bruce J.M., Roshan-Ali Y., . Cleavage of allyl phenyl ethers by bis(benzonitrile)palladium(II) chloride. J. Chem. Res., Synop. 1981:193.
[Google Scholar]
Buckle D.R., Outred D.J., Ross J.W., Smith H., Smith R.J., Spicer B.A., Gasson B.C., . Aryloxyalkyloxy- and aralkyloxy-4-hydroxy-3-nitrocoumarins which inhibit histamine release in the rat and also antagonize the effects of a slow reacting substance of anaphylaxis. J. Med. Chem.. 1979;22:158-168.
[Google Scholar]
Carola, C., Perruchon, S., Buchholz, H., 2004. Preparation of Trihydroxy and Tetrahydroxy Flavones with Anti-oxidative Properties for Use in Cosmetics and Dietary Supplements. Patent EP 1400579.
Cascaval A., Finaru A., Prisecaru M., . Synthesis of some 2-substituted 4-chromanones utilizing o-hydroxyacetophenones. Rev. Roum. Chim.. 1998;43:747-751.
[Google Scholar]
Casellas, P., Floutard, D., Fraisse, P., Jegham, S., 2006. Preparation of 2-Amido-4-phenylthiazole Derivatives as Chemokine Receptors Modulators, in Particular MCP-1 and CCR2b Receptor Antagonists, and Their Therapeutic Application. FR 2876692.
Cassis R., Valderrama J.A., . Studies on quinones. XI. Synthesis of quinones from hydroquinones by using manganese dioxide and acid-impregnated manganese dioxide. Synth. Commun.. 1983;13:347-356.
[Google Scholar]
Cecchi, R., Croci, T., Guzzi, U., Marsault, E., 1999. Phenoxypropanolamines as β3-Adrenergic Agonists. Patent WO 9965895A1.
Chadha T.C., Venkataraman K., . Synthetical experiments in the chromone group. VIII. Derivatives of o-hydroxy-2,5-dihydroxy- and 2,4,5-trihydroxyacetophenone. J. Chem. Soc. 1933:1073-1076.
[Google Scholar]
Chee C.F., Buckle M.J.C., Rahman N.A., . An efficient one-pot synthesis of flavones. Tetrahedron Lett.. 2011;52:3120-3123.
[Google Scholar]
Chee C.F., Lee Y.K., Buckle M.J.C., Abd Rahman N., . Synthesis of (±)-kuwanon V and (±)-dorsterone methyl ethers via Diels-Alder reaction. Tetrahedron Lett.. 2011;52:1797-1799.
[Google Scholar]
Chen A.-H., Kuo W.-B., Chen C.-W., . Photohydrodimerization of 6-methoxyflavone to 6,6″-dimethoxy-2,2″-biflavanones. J. Chin. Chem. Soc.. 2004;51:1389-1394.
[Google Scholar]
Cheng J.-H., Hung C.-F., Yang S.-C., Wang J.-P., Won S.-J., Lin C.-N., . Synthesis and cytotoxic, anti-inflammatory, and anti-oxidant activities of 2′,5′-dialkoxylchalcones as cancer chemopreventive agents. Bioorg. Med. Chem.. 2008;16:7270-7276.
[Google Scholar]
Cooper S.C., Sammes P.G., . (1,5)-Acetyl shifts in cycloadducts derived from 2-acetyl-1,4-benzoquinones. J. Chem. Soc., Chem. Commun. 1980:633-634.
[Google Scholar]
Coowar, D., Couche, E., Koncina, E., Dubois, A., 2010. Preparation of Hydroquinones for Treatment of Neurodegeneration. Patent WO 2010128038.
Cushman M., Zhu H., Geahlen R.L., Kraker A.J., . Synthesis and biochemical evaluation of a series of aminoflavones as potential inhibitors of protein-tyrosine kinases p56^lck, EGFr, and p60^ν-8rc. J. Med. Chem.. 1994;37:3353-3362.
[Google Scholar]
Dandu R.R., Lyons J.A., Raddatz R., Huang Z., Aimone L.D., Hudkins R.L., . Synthesis and evaluation of a new series of 1′-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4′-piperidine] derivatives as high affinity and selective histamine-3 receptor (H3R) antagonists. Bioorg. Med. Chem. Lett.. 2012;22:2151-2153.
[Google Scholar]
De S.K., Gibbs R.A., . An efficient and practical procedure for the synthesis of 4-substituted coumarins. Synthesis 2005:1231-1233.
[Google Scholar]
Desai R.D., Mavani C.K., . Heterocyclic compounds. XX. Kostanecki acetylation of quinacetophenone, quinobenzophenone, and γ-orcacetophenone, and the synthesis of 6-hydroxy- and 5-hydroxychromones and -coumarins. Proc. – Indian Acad. Sci. Sect. A. 1947;25:353-358.
[Google Scholar]
Desai R.D., Trivedi J.J., Trivedi J.P., . Heterocyclic compounds. XXVII. Bromination and nitration of 6-hydroxy-2-methylchromone. J. Sci. Ind. Res.. 1954;13B:328-330.
[Google Scholar]
DeShong P., Li W., Kennington J.W. Jr., Ammon H.L., Leginvs J.M., . A nitrone-based cycloaddition approach to the synthesis of the glycosyl system of nogalomycin, menogaril, and their congeners. J. Org. Chem.. 1991;56:1364-1373.
[Google Scholar]
Dixit M., Sharon A., Maulik P.R., Goel A., . A controlled synthesis of nature-mimicking benzofurans and their corresponding dimers. Synlett 2006:1497-1502.
[Google Scholar]
Doble M., Karthikeyan S., Padmaswar P.A., Akamanchi K.G., . QSAR studies of paeonol analogues for inhibition of platelet aggregation. Bioorg. Med. Chem.. 2005;13:5996-6001.
[Google Scholar]
Dong X., Liu T., Yan J., Wu P., Chen J., Hu Y., . Synthesis, biological evaluation and quantitative structure–activities relationship of flavonoids as vasorelaxant agents. Bioorg. Med. Chem.. 2006;17:716-726.
[Google Scholar]
Doppler T., Schmid H., Hansen H.J., . Photochemistry of 1,2-benzisoxazoles in strongly acidic solution. Helv. Chim. Acta. 1979;62:314-325.
[Google Scholar]
Eggler, J.F., Masamune, H., Marfat, A., Melvin, L.S., 1990. Preparation Substituted 1-[3-(Heteroarylmethoxy)phenyl]alkanols and Related Compounds in the Treatment of Asthma, Arthritis and Related Diseases. Patent EP 391624.
El Telbani E., El Desoky S., Hammad M.A., Abdel Rahman A.H., Schmidt R.R., . C-glycosides of visnagin analogues. Eur. J. Org. Chem.. 1998;1998:2317-2322.
[Google Scholar]
El-Desoky S.I., Abozeid M.A., Kandeel E.A., Abdel-Rahman A.H., . Domino reactions of 3-vinylchromone leading to different heterocyclic compounds. J. Heterocycl. Chem.. 2014;51:1270-1276.
[Google Scholar]
El-Desoky S.I., Al-Shihry S.S., . Synthesis and reactions of some new benzopyranone derivatives with potential biological activities. J. Heterocycl. Chem.. 2008;45:1855-1864.
[Google Scholar]
El-Desoky S.I., Badria F.A., Abozeid M.A., Kandeel E.A., Abdel-Rahman A.H., . Synthesis and antitumor studies of novel benzopyrano-1,2,3-selenadiazole and spiro[benzopyrano]-1,3,4-thiadiazoline derivatives. Med. Chem. Res.. 2013;22:2105-2114.
[Google Scholar]
Erickson R.H., Natalie K.J. Jr., Bock W., Lu Z., Farzin F., Sherrill R.G., Meloni D.J., Patch R.J., Rzesotarski W.J., Clifton J., Pontecorvo M.J., Bailey M.A., Naper K., Karbon W., . (Aminoalkoxy)chromones. Selective σ receptor ligands. J. Med. Chem.. 1992;35:1526-1535.
[Google Scholar]
Feng, K.-C., Li, Y.-S., Yang, J., Zang, H., Gu, H., Ananthavel, S.P., Liang, R.-C., 2004. Novel Fluorinated Dye Stabilizers in Fluorinated Dielectric Solvent. Patent US 20040131958.
Fillaut J.-L., Andries J., Marwaha R.D., Lanoe P.-H., Lohio O., Toupet L., Gareth W.J.A., . Flavonol based ruthenium acetylides as fluorescent chemosensors for lead ions. J. Organomet. Chem.. 2008;693:228-234.
[Google Scholar]
Fisher, M.J., Happ, A.M., Jakubowski, J.A., Kinnick, M.D., Kline, A.D., Martinelli, M.J., Morin Jr., J.M., Paal, M., Rühter, G., Ruterbories, K.J., Sall, D.J., Schotten, T., Skelton, M.A., Stenzel, W., Vasileff, R.T., 1998. Preparation of [(Aminoiminomethyl)benzyloxy]isoquinolinylacetates, -benzopyranylacetates, and Related Compounds as Glycoprotein IIb/IIIa Antagonists. Patent US 5731324.
Fougerousse A., Gonzalez E., Brouillard R., . A convenient method for synthesizing 2-aryl-3-hydroxy-4-oxo-4H-1-benzopyrans or flavonols. J. Org. Chem.. 2000;65:583-586.
[Google Scholar]
Fujise S., Kasahara A., Sato K., Sasaki S., Kamio H., . Syntheses of flavanones. VIII. Syntheses and optical resolution of 6-aminoflavanones. Nippon Kagaku Zasshi. 1954;75:431-435.
[Google Scholar]
Fullam E., Talbot J., Abuhammed A., Westwood I., Davies S.G., Russell A.J., Sim E., . Design, synthesis and structure–activity relationships of 3,5-diaryl-1H-pyrazoles as inhibitors of arylamine N-acetyltransferase. Bioorg. Med. Chem. Lett.. 2013;23:2759-2764.
[Google Scholar]
Gerlach U., Brendel J., Lang H.-J., Paulus E.F., Weidmann K., Brüggemann A., Busch A.E., Suessbrich H., Bleich M., Greger R., . Synthesis and activity of novel and selective I_Ks-channel blockers. J. Med. Chem.. 2001;44:3831-3837.
[Google Scholar]
Gesson J.P., Jacquesy J.C., Jouannetaud M.P., Morellet G., . Hydroxylation of benzaldehyde and aromatic ketones by hydrogen peroxide in a superacid medium. Tetrahedron Lett.. 1983;24:3095-3098.
[Google Scholar]
Gie G.J., . Synthesis of coumarano-3′,2′,2,3-coumarans-estrogenic substances. Arkiv. Kemi, Mineral. Geol.. 1945;19A:15.
[Google Scholar]
Hellwinkel D., Bohnet S., . Dibenzocyclooctene-, dibenzochalcocine-, and diarenochalconinediones. Chem. Ber.. 1987;120:1151-1173.
[Google Scholar]
Horii V.Z., . p-Thiocyanophenylhydrazones. Yakugaku Zasshi. 1937;57:298-306.
[Google Scholar]
Hsieh H.-K., Lee T.-H., Wang J.-P., Wang J.-J., Lin C.-N., . Synthesis and anti-inflammatory effect of chalcones and related compounds. Pharm. Res.. 1998;15:39-46.
[Google Scholar]
Huang K.-S., Li S.-R., Wang Y.-F., Lin Y.-L., Chen Y.-H., Tsai T.-W., Yang C.-H., Wang E.-C., . Synthesis of certain benzoheterocyclic compounds from 2-hydroxyacetophenone via cyclization and ring-closing metathesis. J. Chin. Chem. Soc.. 2005;52:159-167.
[Google Scholar]
Ishizuka N., Matsumura K.-I., Sakai K., Fujimoto M., Mihara S.-I., Yamamori T., . Structure–activity relationships of a novel class of endothelin-a receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3-carboxylic acid (S-1255). 1. Study on structure–activity relationships and basic structure crucial for ETA antagonism. J. Med. Chem.. 2002;45:2041-2055.
[Google Scholar]
Jayashree B.S., Thejaswini J.C., Nayak Y., Kumar D.V., . Synthesis of novel flavone acyl esters and correlation of log P value with antioxidant and antimicrobial activity. Asian J. Chem.. 2010;22:1055-1066.
[Google Scholar]
Jones R.M., Van D.W.R.W., Lindsey C.C., Hoarau C., Ung T., Pettus T.R.R., . A mild anionic method for generating o-quinone methides: facile preparations of ortho-functionalized phenols. J. Org. Chem.. 2001;66:3435-3441.
[Google Scholar]
Kabbe H.-J., Widdig A., . Synthesis and reactions of 4-chromanones. Angew. Chem. Int. Ed.. 1982;21:247-256.
[Google Scholar]
Kallan N.C., Spencer K.L., Blake J.F., Xu R., Heizer J., Bencsik J.R., Mitchell I.S., Gloor S.L., Martinson M., Risom T., Gross S.D., Morales T.H., Wu W.-I., Vigers G.P.A., Brandhuber B.J., Skelton N.J., . Discovery and SAR of spirochromane Akt inhibitors. Bioorg. Med. Chem. Lett.. 2011;21:2410-2414.
[Google Scholar]
Keshk E.M., . Benzofuranyl-pyran-2-ones, -pyridazines, and -pyridones from naturally occurring furochromones (visnagin and khellin) Heteroatom Chem.. 2004;15:85-91.
[Google Scholar]
Khanna R.N., Singh K.P., Sharma J., . Study in crossover Fries migration. Org. Prep. Proced. Int.. 1992;24:687-690.
[Google Scholar]
Kim J.N., Im Y.J., Kim J.M., . Synthesis of ortho-hydroxyacetophenone derivatives from Baylis-Hillman acetates. Tetrahedron Lett.. 2002;43:6597-6600.
[Google Scholar]
Kiyama, R., Kanda, Y., Tada, Y., Fujishita, T., Kawasuji, T., Takechi, S., Fuji, M., 2003. Preparation of Heterocyclic Compounds as Integrase Inhibiting Antiviral Agents. Patent JP 2009161556.
Klinger H., Kolvenbach W., . Formation of acetylquinol from acetaldehyde and quinone in sunlight. Ber. 1898;31:1214-1216.
[Google Scholar]
Kloetzel M.C., Dayton R.P., Abadir B.Y., . Synthetic analogs of cortical hormones. I. Homogentisic acid and α,2,5-trihydroxyacetophenone derivatives from 2,5-diacetoxy-α-diazoacetophenone. J. Org. Chem.. 1955;20:38-49.
[Google Scholar]
Kneppe H., Schneider F., . Rotational viscosity coefficients γ₁ for mixtures of nematic liquid crystals. Mol. Cryst. Liq. Cryst.. 1983;97:219-230.
[Google Scholar]
Ko H.-H., Tsao L.-T., Yu K.-L., Liu C.-T., Wang J.-P., Lin C.-N., . Structure–activity relationship studies on chalcone derivatives the potent inhibition of chemical mediators release. Bioorg. Med. Chem.. 2003;11:105-111.
[Google Scholar]
Kolla S.R., Lee Y.R., . Ca(OH)₂-mediated efficient synthesis of 2-amino-5-hydroxy-4H-chromene derivatives with various substituents. Tetrahedron. 2011;67:8271-8275.
[Google Scholar]
Konieczny M.T., Maciejewski G., Konieczny W., . Selectivity adjustment in the cleavage of allyl phenyl and methyl phenyl ethers with boron trifluoride-methyl sulfide complex. Synthesis 2005:1575-1577.
[Google Scholar]
Konishi F., Esaki S., Kamiya S., . Synthesis of flavonoid glycosides. Part XI. Synthesis and taste of some flavanone and dihydrochalcone glycosides in which carbohydrate moieties are located at differing positions of the aglycons. Agric. Biol. Chem. 1983:1419-1429.
[Google Scholar]
Koskelainen, T., Otsomaa, L., Karjalainen, A., Kotovuori, P., Tenhunen, J., Rasku, S., Nore, P., Tiainen, E., Toermaekangas, O., 2004. Preparation of Phenyl Chromans, Benzo[1,4]dioxins, Indans, and Naphthalenes as Potent Inhibitors of Na⁺/Ca²⁺ Exchange Mechanism for Treatment of Arrhythmias. Patent US 20040235905.
Kraus G.A., Melekhov A., . A direct route to acylhydroquinones from α-keto acids and α-carboxamido acids. Tetrahedron Lett.. 1998;39:3957-3960.
[Google Scholar]
Kupcewicz B., Jarzęcki A.A., Małecka M., Krajewska U., Rozalski M., . Cytotoxic activity of substituted chalcones in terms of molecular electronic properties. Bioorg. Med. Chem. Lett.. 2014;24:4260-4265.
[Google Scholar]
Lal, B., Gangopadhyay, A.K., Rao, V.V.S.V., Gupte, R.D., Gole, G.V., Kulkarni-Almeida, A., Krishnan, S., Panicker, R.B., Pinto, D.S.E., 2010. Preparation of Fused Bicyclic Compounds, in Particular 1-Oxo-1,3-dihydroisoindole Derivatives, as Fibrinogen Receptor Antagonists and Their Use for Treating Thrombotic and Other Diseases. Patent US 20100256161.
Lamba M.S., Kumar S., Makrandi J.K., . One pot synthesis of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones by modified Baker–Venkataraman transformation using microwave irradiation. J. Chem. Res. 2006:133-134.
[Google Scholar]
Le B.B., Windh R.T., Ajello C.W., Leister L.K., Gu M., Chu G.-H., Tuthill P.A., Barker W.M., Koblish M., Wiant D.D., Graczyk T.M., Belanger S., Cassel J.A., Feschenko M.S., Brogdon B.L., Smith S.A., Christ D.D., Derelanko M.J., Kutz S., Little P.J., DeHaven R.N., DeHaven-Hudkins D.L., Dolle R.E., . Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859) J. Med. Chem.. 2008;51:5893-5896.
[Google Scholar]
Legoabe L.J., Petzer A., Petzer J.P., . Selected chromone derivatives as inhibitors of monoamine oxidase. Bioorg. Med. Chem. Lett.. 2012;22:5480-5484.
[Google Scholar]
Letourneau, J.J., Paradkar, V., Ohlmeyer, M.H.J., Dillard, L.W., Baldwin, J.J., Riviello, C.M., Wong, A., Rong, Y., 2005. Nitrogen Heterocycle Biaryls for Osteoporosis and Other Diseases. Patent US 2005222203.
Lim S.S., Jung S.H., Ji J., Shin K.H., Keum S.R., . Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. J. Pharm. Pharmacol.. 2001;53:653-668.
[Google Scholar]
Lindemann H., Romanoff S., . Ring closure of acetyloximes of aromatic o-hydroxyketones. J. Prakt. Chem.. 1929;122:214-231.
[Google Scholar]
Lingam, V.S.P.R., Thomas, A., Khatik, J.Y., Khairatkar, J.N., Kattige, V.G., 2010. Preparation of Chromane Derivatives as TRPV3 Modulators for Treating Pain, Inflammation and Other Disorders. Patent WO 2010128038.
Lyssikatos, J.P., Marmsater, F.P., Zhao, Q., Greschuk, J.M., 2007. Diarylamines as ErbB Inhibitors, Their Preparation, Pharmaceutical Compositions, and Use in Therapy. Patent WO 2007059257.
Ma L., Yang Z., Li C., Zhu Z., Shen X., Hu L., . Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1) J. Enzyme Inhib. Med. Chem.. 2011;26:643-648.
[Google Scholar]
Mandlik P.R., Aswar A.S., . Schiff base metal complexes of chromium(III), manganese(III), iron(III), oxovanadium(IV), zirconium(IV) and dioxouranium(VI) Pol. J. Chem.. 2003;77:129-135.
[Google Scholar]
Manrao M.R., Kohli S., Kalsi P.S., Sharma R.C., Jhooty J.S., . Synthesis and antifungal activity of coumarinimides. Indian J. Chem. Sect. B. 1984;23:1130-1132.
[Google Scholar]
Mays J.R., Hill S.A., Moyers J.T., Blagg B.S.J., . The synthesis and evaluation of flavone and isoflavone chimeras of novobiocin and derrubone. Bioorg. Med. Chem.. 2010;18:249-266.
[Google Scholar]
Mitchell D., Doecke C.W., Hay L.A., Koenig T.M., Wirth D.D., . Ortho-hydroxyl assisted deoxygenation of phenones. Regiochemical control in the synthesis of monoprotected resorcinols and related polyphenolic hydroxyl systems. Tetrahedron Lett.. 1995;36:5335-5338.
[Google Scholar]
Miyamura H., Shiramizu M., Matsubara R., Kobayashi S., . Aerobic oxidation of hydroquinone derivatives catalyzed by polymer-incarcerated platinum catalyst. Angew. Chem. Int. Ed.. 2008;47:8093-8095.
[Google Scholar]
Miyazawa T., Hamada M., Morimoto R., Murashima T., Yamada T., . Highly regioselective propanoylation of dihydroxybenzenes mediated by Candida antarctica lipase B in organic solvents. Tetrahedron Lett.. 2008;49:175-178.
[Google Scholar]
Mizuguchi E., Takemoto M., Achiwa K., . An enzyme-catalyzed synthesis of natural α-tocopherol. Tetrahedron Asymmetry. 1993;4:1961-1964.
[Google Scholar]
Mmutlane E.M., Michael J.P., Green I.R., de K.C.B., . The synthesis of ventiloquinone L, the monomer of cardinalin 3. Org. Biomol. Chem.. 2004;2:2461-2470.
[Google Scholar]
Moghaddam F.M., Ghaffarzadeh M., Abdi-Oskoui S.H., . Tandem Fries reaction-conjugate addition under microwave irradiation in dry media. One-pot synthesis of flavanones. J. Chem. Res., Synop. 1999:574-575.
[Google Scholar]
Moorthy N.S.H.N., Singh R.J., Singh H.P., Gupta S.D., . Synthesis, biological evaluation and in silico metabolic and toxicity prediction of some flavanone derivatives. Chem. Pharm. Bull.. 2006;54:1384-1390.
[Google Scholar]
Mujica-Fernaud, T., Buchholz, H., Carola, C., Rautenberg, W., Sirrenberg, C., 2004. Preparation of Oxadiazolylchromones as Modulators of Tyrosine Kinase Signal Transduction. Patent EP 1426372.
Müller H., Paul M., Hartmann D., Huch V., Blaesius D., Koeberle A., Werz O., Jauch J., . Total synthesis of myrtucommulone A. Angew. Chem. Int. Ed.. 2010;49:2045-2049.
[Google Scholar]
Mutai P., Pavadai E., Wiid I., Ngwane A., Baker B., Chibale K., . Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin. Bioorg. Med. Chem. Lett.. 2015;25:2510-2513.
[Google Scholar]
Naeimi H., Moradi L., . Microwave assisted direct ortho-acylation of phenol and naphthol derivatives by BF₃·(C₂H₅)₂O. Bull. Chem. Soc. Jpn.. 2005;78:284-287.
[Google Scholar]
Naeimi H., Moradi L., . Regioselective ortho-acylation of phenol and naphthol derivatives catalyzed by FeCl₃ under microwave conditions. Russ. J. Org. Chem.. 2007;43:1757-1759.
[Google Scholar]
Nair M.L.H.K., Shamla L.J., . Synthesis, spectral, thermal and antibacterial studies of copper(II) complexes of a Schiff base derived from 2,3-dimethyl-1-phenyl-4-aminopyrazol-5-one. Indian Chem. Soc.. 2009;86:913-919.
[Google Scholar]
Nam N.-H., Kim Y., You Y.-J., Hong D.-H., Kim H.-M., Ahn B.-Z., . Cytotoxic 2′,5′-dihydroxychalcones with unexpected antiangiogenic activity. Eur. J. Med. Chem.. 2003;38:179-187.
[Google Scholar]
Neelakantan S., Raman P.V., Tinabaye A., . A new and convenient synthesis of 4-methyl-3-phenylcoumarins and 3-phenylcoumarins. Indian J. Chem. Sect. B. 1982;21:256-267.
[Google Scholar]
Nicolosi G., Piattelli M., Sanfilippo C., . Lipase-catalyzed regioselective protection of hydroxyl groups in aromatic dihydroxy aldehydes and ketones. Tetrahedron. 1993;49:3143-3148.
[Google Scholar]
Niedermeyer T.H.J., Mikolasch A., Lalk M., . Nuclear amination catalyzed by fungal laccases: reaction products of p-hydroquinones and primary aromatic amines. J. Org. Chem.. 2005;70:2002-2008.
[Google Scholar]
Nussbaumer P., Lehr P., Billich A.J., . 2-Substituted 4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase. Med. Chem.. 2002;45:4310-4320.
[Google Scholar]
Oganesyan E.T., Vasilenko Y.K., Khachatryan M.M., Pyshchev A.I., . Synthesis of flavone derivatives having hypolipidemic activities. Khim.-Farm. Zh.. 1989;23:1353-1356.
[Google Scholar]
Park H.R., Park K.-S., Chong Y., . 2-Arylmethylaminomethyl-5,6-dihydroxychromone derivatives with selective anti-HCV activity. Bioorg. Med. Chem. Lett.. 2011;21:3202-3205.
[Google Scholar]
Parveen M., Ali A., Alam M., Khan A., Ahmad A., . Synthesis, characterization, biological evaluation and in silico screening of oxadiazinanones. Med. Chem. Res.. 2013;22:3085-3095.
[Google Scholar]
Paul S., Nanda P., Gupta R., Loupy A., . Zinc mediated Friedel-Crafts acylation in solvent-free conditions under microwave irradiation. Synthesis 2003:2877-2881.
[Google Scholar]
Paul S., Nanda P., Gupta R., . Synthesis of α-bromoalkanones using urea–hydrogen peroxide complex and sodium bromide over silica gel–acetic acid. Indian J. Chem. Sect. B. 2005;44:184-187.
[Google Scholar]
Pearce B.C., Parker R.A., Deason M.E., Dischino D.D., Gillespie E., Qureshi A.A., Wright J.J.K., Volk K., . Inhibitors of cholesterol biosynthesis. 2. hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogs of the tocotrienols. J. Med. Chem.. 1994;37:526-541.
[Google Scholar]
Petrov M.L., Androsov D.A., Abramov M.A., Abramova I.P., Dehaen W., Lyakhovetskii Y.I., . Synthesis and reactivity of 5- and 6-hydroxybenzo[b]furan-2-selenolates. Russ. J. Org. Chem.. 2006;42:1521-1527.
[Google Scholar]
Petrov M.L., Dehaen W., Abramov M.A., Abramova I.P., Androsov D.A., . 4-(2-Hydroxyaryl)-1,2,3-thiadiazoles as a source of 2-benzofuranthiolates. Russ. J. Org. Chem.. 2002;38:1510-1518.
[Google Scholar]
Pillay A., Rousseau A.L., Fernandes M.A., de Koning C.B., . Wacker oxidation methodology for the synthesis of the benzo-fused acetal core of marticin. Tetrahedron. 2012;68:7116-7121.
[Google Scholar]
Qin D.-D., Yang Z.-Y., Li T.-R., Qi G.-F., . DNA-binding study of nickel(II) and zinc(II) complexes with two novel chromenone-based Schiff-base ligands. Helv. Chim. Acta. 2009;92:525-535.
[Google Scholar]
Rajakumar P., Mohammed A.R.A., Balu P.M., Murugesan K., . Synthesis, characterization, and anti-bacterial efficacy of some novel cyclophane amide. Bioorg. Med. Chem.. 2006;14:7458-7467.
[Google Scholar]
Rane R.A., Sahu N.U., Gutte S.D., Mahajan A.A., Shah C.P., Bangalore P., . Synthesis and evaluation of novel marine bromopyrrole alkaloid-based hybrids as anticancer agents. Eur. J. Med. Chem.. 2013;63:793-799.
[Google Scholar]
Ravichandran S., Singh N., Donnelly D., Migliore M., Johnson P., Fishwick C., Luke B.T., Martin B., Maudsley S., Fugmann S.D., Moaddel R., . Pharmacophore model of the quercetin binding site of the SIRT6 protein. J. Mol. Graph. Modell.. 2014;49:38-46.
[Google Scholar]
Roma G., Di B.M., Carrieri A., Grossi G., Leoncini G., Grazia S.M., Carotti A., . Coumarin, chromone, and 4(3H)-pyrimidinone novel bicyclic and tricyclic derivatives as antiplatelet agents: synthesis, biological evaluation, and comparative molecular field analysis. Bioorg. Med. Chem.. 2003;11:123-138.
[Google Scholar]
Roma G., Di B.M., Grossi G., Piras D., Leoncini G., Bruzzese D., Signorello M.G., Fossa P., Mosti L., . Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two most effective compounds described and molecular modeling study on their interactions with phosphodiesterase 3A catalytic site. J. Med. Chem.. 2007;50:2886-2895.
[Google Scholar]
Rosenmund K.W., Lohfert H., . Synthesis of polyphenol ketones. Ber. Dtsch. Chem. Ges. B. 1928;61B:2601-2607.
[Google Scholar]
Ruchirawat S., Mutarapat T., . An efficient synthesis of lamellarin alkaloids: synthesis of lamellarin G trimethyl ether. Tetrahedron Lett.. 2001;42:1205-1208.
[Google Scholar]
Russell A., Clark S.F., . Constitution of natural tannins. VI. Coloring matters derived from 2,5-dihydroxyacetophenone. J. Am. Chem. Soc.. 1939;61:2651-2658.
[Google Scholar]
Russell A., Happoldt W.B. Jr., . Constitution of natural tannins. VIII. Coloring matters derived from anthracene-9-aldehyde. J. Am. Chem. Soc.. 1942;64:1101-1103.
[Google Scholar]
Sakamoto, K., Okuyama, K., 2014. Polymerizable Compound, Polymerizable Composition, Polymer, and Optically Anisotropic Body. Patent EP 2719683.
Sakamoto, K., Okuyama, K., 2014. Polymerizable Compound, Polymerizable Composition, Polymer, and Optically Anisotropic Material. Patent EP 2703385.
Salama T.A., Ismail M.A., Khalil A.-G.M., Elmorsy S.S., . Silicon-assisted O-heterocyclic synthesis: mild and efficient one-pot syntheses of (E)-3-benzylideneflavanones, coumarin-3-carbonitriles/carboxamides, and benzannulated spiropyran derivatives. Arkivoc 2012:242-253.
[Google Scholar]
Salavati-Niasari M., Fereshteh Z., Davar F., . Synthesis of cobalt nanoparticles from [bis(2-hydroxyacetophenato)cobalt(II)] by thermal decomposition. Polyhedron. 2009;28:1065-1068.
[Google Scholar]
Sanchez-Viesca F., Berros M., Gomez M.R., . Intramolecular weak hydrogen bonds in substituted 4-arylthiazoles. Heterocycl. Commun.. 2003;9:165-170.
[Google Scholar]
Sato S., Watanabe T., Kumagai H., Kitamura N., Matsuba S., Kumazawa T., Onodera J.-I., Suzuki M., . Convenient synthesis of 1,6,7,8-substituted 2-(3′,4′-substituted-phenyl)-4-quinolones via a 4-ethoxyflavylium salt. J. Heterocycl. Chem.. 1999;36:1189-1193.
[Google Scholar]
Schönberg A., Badran N., Starkowsky N.A., . Furo-chromones and -coumarins. VII. Degradation of visnagin, khellin and related substances; experiments with chromic acid and hydrogen peroxide; and a synthesis of eugenitin. J. Am. Chem. Soc.. 1953;75:4992-4995.
[Google Scholar]
Sharghi H., Kaboudin B., . Alumina in methanesulfonic acid (AMA) as a new efficient reagent for direct acylation of phenol derivatives and Fries rearrangement. A convenient synthesis of o-hydroxyarylketones. J. Chem. Res. 1998:2678-2695. (Miniprint)
[Google Scholar]
Sharma S.C., Swami M.P., Sharma R.C., . Nitrogen heterocyclic analogs of cannabinoids. Part I: synthesis of 6H-indolo[1,2-c][1,3]benzoxazine systems and evaluation of their biological activities. J. Indian Chem. Soc.. 1983;60:1002-1004.
[Google Scholar]
Singh H.P., Chauhan C.S., Pandeya S.N., Sharma C.S., . Chalconsemicarbazone: a new scaffold for antiepileptic drug discovery. J. Chil. Chem. Soc.. 2010;55:103-106.
[Google Scholar]
Sircar I., Hoefle M., Maxwell R.E., . Phenylenebis(oxy)bis[2,2-dimethylpentanoic acids]: agents that elevate high-density lipoproteins. J. Med. Chem.. 1983;26:1020-1027.
[Google Scholar]
Srimal R.C., Kar K., . Synthesis of 2,4-, 2,5- and 2,6-bis[3-substituted amino(propoxy/2-hydroxypropoxy)]acetophenones as biodynamic agents. Indian J. Chem. Sect. B. 1983;22:140-145.
[Google Scholar]
Summa V., Petrocchi A., Pace P., Matassa V.G., De F.R., Altamura S., Tomei L., Koch U., Neuner P., . Discovery of α,γ-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. J. Med. Chem.. 2004;47:14-17.
[Google Scholar]
Takabatake T., Miyazawa T., Kojo M., Hasegawa M., . Synthesis of phenazine 5,10-dioxides from benzofuroxan catalyzed by molecular sieves. Heterocycles. 2000;53:2151-2162.
[Google Scholar]
Thapliyal P.C., Aggarwal L.K., . Thermal cross Fries acyl and benzoyl migrations from aromatic diesters to phenols. Indian J. Chem. Sect. B. 2000;39:706-708.
[Google Scholar]
Tripathi A.K., Koul S., Taneja S.C., . Microwave-assisted facile and efficient synthesis of benzopyran. Indian J. Chem. Sect. B. 2009;48:301-304.
[Google Scholar]
Tu Q.-D., Li D., Sun Y., Han X.-Y., Yi F., Sha Y., Ren Y.-L., Ding M.-W., Feng L.-L., Wan J., . Design and syntheses of novel N′-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide as inhibitors of cyanobacterial fructose-1,6-sedoheptulose-1,7-bisphosphatase. Bioorg. Med. Chem.. 2013;21:2826-2831.
[Google Scholar]
Uchil V.R., Joshi V., . Montmorillonite K10-AlCl3 catalyzed enolization. A bifunctional system for selective bromination of hydroxyacetophenones. Indian J. Chem. Sect. B. 2003;42:408-411.
[Google Scholar]
Vandenberghe A., Willems J.F., . Sulfonation of alkyl hydroquinones. B. Soc. Chim. Belg.. 1965;74:397-406.
[Google Scholar]
Vasquez-Martinez Y., Ohri R.V., Kenyon V., Holman T.R., Sepulveda-Boza S., . Structure–activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. Bioorg. Med. Chem.. 2007;15:7408-7425.
[Google Scholar]
Veibel S., Schmidt H.W., . Diagnostic value of the titration curves of the p-carboxyphenylhydrazones of hydroxy-substituted aromatic aldehydes and ketones. Acta Chem. Scand.. 1948;2:545-549.
[Google Scholar]
Verheggen F., Ryne C., Olsson P.O.C., Arnaud L., Lognay G., Hoegberg H.E., Persson D., Haubruge E., Loefstedt C., . Electrophysiological and behavioral activity of secondary metabolites in the confused flour beetle, Tribolium confusum. J. Chem. Ecol.. 2007;33:525-539.
[Google Scholar]
Verma J.K., Verma G.S.P., . Dimeric copper(II), nickel(II) and cobalt(II) complexes of tridentate ONN donor ligands. J. Indian Chem. Soc.. 1983;60:786-787.
[Google Scholar]
Vyas G.N., Shah N.M., . Chalcones from quinacetophenone. J. Indian Chem. Soc.. 1949;26:273-276.
[Google Scholar]
Wellington K.W., Steenkamp P., Brady D., . Diamination by N-coupling using a commercial laccase. Bioorg. Med. Chem.. 2010;18:1406-1414.
[Google Scholar]
Willstaedt H., Michaelis M., . 1,4-Dihydroxy-2-acetylanthraquinone. Sven. Kem. Tidskr.. 1938;50:274-278.
[Google Scholar]
Wissner A., Carroll M.L., Green K.E., Kerwar S.S., Pickett W.C., Schaub R.E., Torley L.W., Wrenn S., Kohler C.A., . Analogs of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor. J. Med. Chem.. 1992;35:1650-1662.
[Google Scholar]
Witiak D.T., Kim S.K., Tehim A.K., Sternitzke K.D., McCreery R.L., Kim S.U., Feller D.R., Romstedt K.J., Kamanna V.S., Newman H.A.I., . Synthetic aci-reductones. 3,4-Dihydroxy-2H-1-benzopyran-2-ones and their cis- and trans-4a,5,6,7,8,8a-hexahydro diastereomers. Antiaggregatory, antilipidemic, and redox properties compared to the 4-substituted 2-hydroxytetronic acids. J. Med. Chem.. 1988;31:1437-1445.
[Google Scholar]
Won S.-J., Liu C.-T., Tsao L.-T., Weng J.-R., Ko H.-H., Wang J.-P., Lin C.-N., . Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur. J. Med. Chem.. 2005;40:103-112.
[Google Scholar]
Wu S.-Y., Ito S., Eto M., . Metabolic formation of 4-methyl-4H-1,3,2-benzodioxaphosphorins from bis(o-ethylphenyl) phenylphosphonates in house flies. Agric. Biol. Chem.. 1987;51:2935-2942.
[Google Scholar]
Wymann W.E., Davis R., Patterson J.W. Jr., Pfister J.R., . Selective alkylations of certain phenolic and enolic functions with lithium carbonate-alkyl halide. Synth. Commun.. 1988;18:1379-1384.
[Google Scholar]
Yamaguchi S., Saitoh A., Kawase Y., . The revised structure of a dihydrobenzofuran derivative isolated from Lasiolaena morii. Bull. Chem. Soc. Jpn.. 1986;59:3983-3984.
[Google Scholar]
Yamato M., Hashigaki K., Tsutsumi A., Tasaka K., . Synthesis and structure–activity relationship of spiro[isochroman-piperidine] analogs for inhibition of histamine release. II. Chem. Pharm. Bull.. 1981;29:3494-3498.
[Google Scholar]
Zbancioc A.M., Miron A., Tuchilus C., Rotinberg P., Mihai C.T., Mangalagiu I.I., Zbancioc G., . Synthesis and in vitro analysis of novel dihydroxyacetophenone derivatives with antimicrobial and antitumor activities. Med. Chem.. 2014;10:476-483.
[Google Scholar]
Zbancioc G.N., Zbancioc A.M.V., Mantu D., Miron A., Tanase C., Mangalagiu I.I., . Ultrasound-assisted synthesis of highly functionalized acetophenone derivatives in heterogeneous catalysis. Rev. Roum. Chim.. 2010;55:983-987.
[Google Scholar]
Zhao H., Brandt G.E., Galam L., Matts R.L., Blagg B.S.J., . Identification and initial SAR of silybin: an Hsp90 inhibitor. Bioorg. Med. Chem. Lett.. 2011;21:2659-2664.
[Google Scholar]
Zhao W., Sun J., Xiang H., Zeng Y.-Y., Li X.-B., Xiao H., Chen D.-Y., Ma R.-L., . Synthesis and biological evaluation of new flavonoid fatty acid esters with anti-adipogenic and enhancing glucose consumption activities. Bioorg. Med. Chem.. 2011;19:3192-3203.
[Google Scholar]

Show Sections

[1] Abdel-Rahman A.H., Hammouda M.A.A., El-Desoky S.I., . Synthesis of some new azole, azepine, pyridine, and pyrimidine derivatives using 6-hydroxy-4H-4-oxo[1]-benzopyran-3-carboxaldehyde as a versatile starting material. Heteroat. Chem.. 2005;16:20-27.
[Google Scholar]

[2] Agarwal S.K., Saxena R.C.J., . Synthesis, characterization and screening of antibacterial activity of some new Mannich bases. Indian Chem. Soc.. 1980;57:1240-1241.
[Google Scholar]

[3] Aggarwal R., Giles R.G.F., Green I.R., Oosthuizen F.J., Taylor C.P., . Syntheses in enantiopure form of four diastereoisomeric naphthopyranquinones derived from aphid insect pigments. Org. Biomol. Chem.. 2005;3:263-273.
[Google Scholar]

[4] Ali M.H., Niedbalski M., Bohnert G., Bryant D., . Silica-gel-supported ceric ammonium nitrate (CAN). A simple and efficient solid-supported reagent for oxidation of oxygenated aromatic compounds to quinones. Synth. Commun.. 2006;36:1751-1759.
[Google Scholar]

[5] Amin G.C., Shah N.M.J., . Fries migration. V. Fries migration of 4-methoxyquinol esters and 4-benzoxyquinol acetate. Indian Chem. Soc.. 1950;27:531-534.
[Google Scholar]

[6] Aponte J.C., Verástegui M., Málaga E., Zimic M., Quiliano M., Vaisberg A.J., Gilman R.H., Hammond G.B., . Synthesis, cytotoxicity, and anti-Trypanosoma cruzi activity of new chalcones. J. Med. Chem.. 2008;51:6230-6234.
[Google Scholar]

[7] Arvanitis A.G., Scholfield E.L., Grigoriadis D., Heytler P.G., Bowdle J., Chorvat R.J., . Alkylbenzyl ethers of hydroquinones as monoamine oxidase B inhibitors. Bioorg. Med. Chem. Lett.. 1996;6:115-120.
[Google Scholar]

[8] Avupati V.R., Yejella R.P., Akula A., Guntuku G.S., Doddi B.R., Vutla V.R., Anagani S.R., Adimulam L.S., Vyricharla A.K., . Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents. Bioorg. Med. Chem. Lett.. 2012;22:6442-6450.
[Google Scholar]

[9] Baker Jr., J.R., Huang, B.M., Thomas, T.P., 2011. Prodrug Complexes and Related Methods of Use. Patent WO 2011002852.

[10] Baker W., . Attempts to synthesize 5,6-dihydroxyflavone (primetin) J. Chem. Soc. 1934:1953-1954.
[Google Scholar]

[11] Bandgar B.P., Uppalla L.S., Sadavarte V.S., . Lithium perchlorate and lithium bromide catalyzed solvent free one pot rapid synthesis of 3-carboxycoumarins under microwave irradiation. J. Chem. Res., Synop. 2002:40-41.
[Google Scholar]

[12] Banerji A., Goomer N.C., . Synthesis of naturally occurring 6-oxygenated-2,2-dimethylchromenes. Indian J. Chem. Sect. B. 1984;23:885-886.
[Google Scholar]

[13] Becknell N.C., Dandu R.R., Lyons J.A., Aimone L.D., Raddatz R., Hudkins R.L., . Synthesis and evaluation of 4-alkoxy-[1′-cyclobutyl-spiro(3,4-dihydrobenzopyran-2,4′-piperidine)] analogues as histamine-3 receptor antagonists. Bioorg. Med. Chem. Lett.. 2012;22:186-189.
[Google Scholar]

[14] Beddoes R.L., Bruce J.M., Finch H., Heelam L.M.J., Hunt I.D., Mills O.S., . Benzoquinones and related compounds. Part 4. Thermolysis of the Diels-Alder adduct of 2-acetyl-5,6-dichloro-1,4-benzoquinone and cyclopentadiene: evidence for a partial retro-diene reaction. J. Chem. Soc. Perkin Trans.. 1981;1:2670-2676.
[Google Scholar]

[15] Belanger, P.C., Scheigetz, J., Rokach, J., 1985. Benzofuran and Benzothiophene Derivatives and Their Use in Inhibiting Mammalian Leukotriene Biosynthesis. Patent EP 165810.

[16] Biegasiewicz K.F., Gordon J.S. IV, Rodriguez D.A., Priefer R., . Development of a general approach to the synthesis of a library of isoflavonoid derivatives. Tetrahedron Lett.. 2014;55:5210-5212.
[Google Scholar]

[17] Billich, A., Nussbaumer, P., Schreiner, E., Schuster, I., 1999. Preparation of Chromanone and Thiochromanone Derivatives as Steroid Sulfatase Inhibitors. Patent WO 9952890.

[18] Booth B.L., Noori G.F.M., . The chemistry of nitrilium salts. Part 1. Acylation of phenols and phenol ethers with nitriles and trifluoromethanesulfonic acid. J. Chem. Soc. Perkin Trans.. 1980;1:2894-2900.
[Google Scholar]

[19] Boyer J.L., Krum J.E., Myers M.C., Fazal A.N., Wigal C.T., . Synthetic utility and mechanistic implications of the Fries rearrangement of hydroquinone diesters in boron trifluoride complexes. J. Org. Chem.. 2000;65:4712-4714.
[Google Scholar]

[20] Brimble M.A., Burgess C., Halim R., Petersson M., Ray J., . Synthesis of pyrrolo[3,2-b]benzofurans and pyrrolo[3,2-b]naphthofurans via addition of a silyloxypyrrole to activated quinones. Tetrahedron. 2004;60:5751-5758.
[Google Scholar]

[21] Brubaker A.N., De R.J., Whitmer W.L., . Synthesis and rat lens aldose reductase inhibitory activity of some benzopyran-2-ones. J. Med. Chem.. 1986;29:1094-1099.
[Google Scholar]

[22] Bruce D.B., Sorrie A.J.S., Thomson R.H., . Reactions in fused aluminum chloride–sodium chloride. J. Chem. Soc. 1953:2403-2406.
[Google Scholar]

[23] Bruce J.M., Roshan-Ali Y., . Cleavage of allyl phenyl ethers by bis(benzonitrile)palladium(II) chloride. J. Chem. Res., Synop. 1981:193.
[Google Scholar]

[24] Buckle D.R., Outred D.J., Ross J.W., Smith H., Smith R.J., Spicer B.A., Gasson B.C., . Aryloxyalkyloxy- and aralkyloxy-4-hydroxy-3-nitrocoumarins which inhibit histamine release in the rat and also antagonize the effects of a slow reacting substance of anaphylaxis. J. Med. Chem.. 1979;22:158-168.
[Google Scholar]

[25] Carola, C., Perruchon, S., Buchholz, H., 2004. Preparation of Trihydroxy and Tetrahydroxy Flavones with Anti-oxidative Properties for Use in Cosmetics and Dietary Supplements. Patent EP 1400579.

[26] Cascaval A., Finaru A., Prisecaru M., . Synthesis of some 2-substituted 4-chromanones utilizing o-hydroxyacetophenones. Rev. Roum. Chim.. 1998;43:747-751.
[Google Scholar]

[27] Casellas, P., Floutard, D., Fraisse, P., Jegham, S., 2006. Preparation of 2-Amido-4-phenylthiazole Derivatives as Chemokine Receptors Modulators, in Particular MCP-1 and CCR2b Receptor Antagonists, and Their Therapeutic Application. FR 2876692.

[28] Cassis R., Valderrama J.A., . Studies on quinones. XI. Synthesis of quinones from hydroquinones by using manganese dioxide and acid-impregnated manganese dioxide. Synth. Commun.. 1983;13:347-356.
[Google Scholar]

[29] Cecchi, R., Croci, T., Guzzi, U., Marsault, E., 1999. Phenoxypropanolamines as β3-Adrenergic Agonists. Patent WO 9965895A1.

[30] Chadha T.C., Venkataraman K., . Synthetical experiments in the chromone group. VIII. Derivatives of o-hydroxy-2,5-dihydroxy- and 2,4,5-trihydroxyacetophenone. J. Chem. Soc. 1933:1073-1076.
[Google Scholar]

[31] Chee C.F., Buckle M.J.C., Rahman N.A., . An efficient one-pot synthesis of flavones. Tetrahedron Lett.. 2011;52:3120-3123.
[Google Scholar]

[32] Chee C.F., Lee Y.K., Buckle M.J.C., Abd Rahman N., . Synthesis of (±)-kuwanon V and (±)-dorsterone methyl ethers via Diels-Alder reaction. Tetrahedron Lett.. 2011;52:1797-1799.
[Google Scholar]

[33] Chen A.-H., Kuo W.-B., Chen C.-W., . Photohydrodimerization of 6-methoxyflavone to 6,6″-dimethoxy-2,2″-biflavanones. J. Chin. Chem. Soc.. 2004;51:1389-1394.
[Google Scholar]

[34] Cheng J.-H., Hung C.-F., Yang S.-C., Wang J.-P., Won S.-J., Lin C.-N., . Synthesis and cytotoxic, anti-inflammatory, and anti-oxidant activities of 2′,5′-dialkoxylchalcones as cancer chemopreventive agents. Bioorg. Med. Chem.. 2008;16:7270-7276.
[Google Scholar]

[35] Cooper S.C., Sammes P.G., . (1,5)-Acetyl shifts in cycloadducts derived from 2-acetyl-1,4-benzoquinones. J. Chem. Soc., Chem. Commun. 1980:633-634.
[Google Scholar]

[36] Coowar, D., Couche, E., Koncina, E., Dubois, A., 2010. Preparation of Hydroquinones for Treatment of Neurodegeneration. Patent WO 2010128038.

[37] Cushman M., Zhu H., Geahlen R.L., Kraker A.J., . Synthesis and biochemical evaluation of a series of aminoflavones as potential inhibitors of protein-tyrosine kinases p56^lck, EGFr, and p60^ν-8rc. J. Med. Chem.. 1994;37:3353-3362.
[Google Scholar]

[38] Dandu R.R., Lyons J.A., Raddatz R., Huang Z., Aimone L.D., Hudkins R.L., . Synthesis and evaluation of a new series of 1′-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4′-piperidine] derivatives as high affinity and selective histamine-3 receptor (H3R) antagonists. Bioorg. Med. Chem. Lett.. 2012;22:2151-2153.
[Google Scholar]

[39] De S.K., Gibbs R.A., . An efficient and practical procedure for the synthesis of 4-substituted coumarins. Synthesis 2005:1231-1233.
[Google Scholar]

[40] Desai R.D., Mavani C.K., . Heterocyclic compounds. XX. Kostanecki acetylation of quinacetophenone, quinobenzophenone, and γ-orcacetophenone, and the synthesis of 6-hydroxy- and 5-hydroxychromones and -coumarins. Proc. – Indian Acad. Sci. Sect. A. 1947;25:353-358.
[Google Scholar]

[41] Desai R.D., Trivedi J.J., Trivedi J.P., . Heterocyclic compounds. XXVII. Bromination and nitration of 6-hydroxy-2-methylchromone. J. Sci. Ind. Res.. 1954;13B:328-330.
[Google Scholar]

[42] DeShong P., Li W., Kennington J.W. Jr., Ammon H.L., Leginvs J.M., . A nitrone-based cycloaddition approach to the synthesis of the glycosyl system of nogalomycin, menogaril, and their congeners. J. Org. Chem.. 1991;56:1364-1373.
[Google Scholar]

[43] Dixit M., Sharon A., Maulik P.R., Goel A., . A controlled synthesis of nature-mimicking benzofurans and their corresponding dimers. Synlett 2006:1497-1502.
[Google Scholar]

[44] Doble M., Karthikeyan S., Padmaswar P.A., Akamanchi K.G., . QSAR studies of paeonol analogues for inhibition of platelet aggregation. Bioorg. Med. Chem.. 2005;13:5996-6001.
[Google Scholar]

[45] Dong X., Liu T., Yan J., Wu P., Chen J., Hu Y., . Synthesis, biological evaluation and quantitative structure–activities relationship of flavonoids as vasorelaxant agents. Bioorg. Med. Chem.. 2006;17:716-726.
[Google Scholar]

[46] Doppler T., Schmid H., Hansen H.J., . Photochemistry of 1,2-benzisoxazoles in strongly acidic solution. Helv. Chim. Acta. 1979;62:314-325.
[Google Scholar]

[47] Eggler, J.F., Masamune, H., Marfat, A., Melvin, L.S., 1990. Preparation Substituted 1-[3-(Heteroarylmethoxy)phenyl]alkanols and Related Compounds in the Treatment of Asthma, Arthritis and Related Diseases. Patent EP 391624.

[48] El Telbani E., El Desoky S., Hammad M.A., Abdel Rahman A.H., Schmidt R.R., . C-glycosides of visnagin analogues. Eur. J. Org. Chem.. 1998;1998:2317-2322.
[Google Scholar]

[49] El-Desoky S.I., Abozeid M.A., Kandeel E.A., Abdel-Rahman A.H., . Domino reactions of 3-vinylchromone leading to different heterocyclic compounds. J. Heterocycl. Chem.. 2014;51:1270-1276.
[Google Scholar]

[50] El-Desoky S.I., Al-Shihry S.S., . Synthesis and reactions of some new benzopyranone derivatives with potential biological activities. J. Heterocycl. Chem.. 2008;45:1855-1864.
[Google Scholar]

[51] El-Desoky S.I., Badria F.A., Abozeid M.A., Kandeel E.A., Abdel-Rahman A.H., . Synthesis and antitumor studies of novel benzopyrano-1,2,3-selenadiazole and spiro[benzopyrano]-1,3,4-thiadiazoline derivatives. Med. Chem. Res.. 2013;22:2105-2114.
[Google Scholar]

[52] Erickson R.H., Natalie K.J. Jr., Bock W., Lu Z., Farzin F., Sherrill R.G., Meloni D.J., Patch R.J., Rzesotarski W.J., Clifton J., Pontecorvo M.J., Bailey M.A., Naper K., Karbon W., . (Aminoalkoxy)chromones. Selective σ receptor ligands. J. Med. Chem.. 1992;35:1526-1535.
[Google Scholar]

[53] Feng, K.-C., Li, Y.-S., Yang, J., Zang, H., Gu, H., Ananthavel, S.P., Liang, R.-C., 2004. Novel Fluorinated Dye Stabilizers in Fluorinated Dielectric Solvent. Patent US 20040131958.

[54] Fillaut J.-L., Andries J., Marwaha R.D., Lanoe P.-H., Lohio O., Toupet L., Gareth W.J.A., . Flavonol based ruthenium acetylides as fluorescent chemosensors for lead ions. J. Organomet. Chem.. 2008;693:228-234.
[Google Scholar]

[55] Fisher, M.J., Happ, A.M., Jakubowski, J.A., Kinnick, M.D., Kline, A.D., Martinelli, M.J., Morin Jr., J.M., Paal, M., Rühter, G., Ruterbories, K.J., Sall, D.J., Schotten, T., Skelton, M.A., Stenzel, W., Vasileff, R.T., 1998. Preparation of [(Aminoiminomethyl)benzyloxy]isoquinolinylacetates, -benzopyranylacetates, and Related Compounds as Glycoprotein IIb/IIIa Antagonists. Patent US 5731324.

[56] Fougerousse A., Gonzalez E., Brouillard R., . A convenient method for synthesizing 2-aryl-3-hydroxy-4-oxo-4H-1-benzopyrans or flavonols. J. Org. Chem.. 2000;65:583-586.
[Google Scholar]

[57] Fujise S., Kasahara A., Sato K., Sasaki S., Kamio H., . Syntheses of flavanones. VIII. Syntheses and optical resolution of 6-aminoflavanones. Nippon Kagaku Zasshi. 1954;75:431-435.
[Google Scholar]

[58] Fullam E., Talbot J., Abuhammed A., Westwood I., Davies S.G., Russell A.J., Sim E., . Design, synthesis and structure–activity relationships of 3,5-diaryl-1H-pyrazoles as inhibitors of arylamine N-acetyltransferase. Bioorg. Med. Chem. Lett.. 2013;23:2759-2764.
[Google Scholar]

[59] Gerlach U., Brendel J., Lang H.-J., Paulus E.F., Weidmann K., Brüggemann A., Busch A.E., Suessbrich H., Bleich M., Greger R., . Synthesis and activity of novel and selective I_Ks-channel blockers. J. Med. Chem.. 2001;44:3831-3837.
[Google Scholar]

[60] Gesson J.P., Jacquesy J.C., Jouannetaud M.P., Morellet G., . Hydroxylation of benzaldehyde and aromatic ketones by hydrogen peroxide in a superacid medium. Tetrahedron Lett.. 1983;24:3095-3098.
[Google Scholar]

[61] Gie G.J., . Synthesis of coumarano-3′,2′,2,3-coumarans-estrogenic substances. Arkiv. Kemi, Mineral. Geol.. 1945;19A:15.
[Google Scholar]

[62] Hellwinkel D., Bohnet S., . Dibenzocyclooctene-, dibenzochalcocine-, and diarenochalconinediones. Chem. Ber.. 1987;120:1151-1173.
[Google Scholar]

[63] Horii V.Z., . p-Thiocyanophenylhydrazones. Yakugaku Zasshi. 1937;57:298-306.
[Google Scholar]

[64] Hsieh H.-K., Lee T.-H., Wang J.-P., Wang J.-J., Lin C.-N., . Synthesis and anti-inflammatory effect of chalcones and related compounds. Pharm. Res.. 1998;15:39-46.
[Google Scholar]

[65] Huang K.-S., Li S.-R., Wang Y.-F., Lin Y.-L., Chen Y.-H., Tsai T.-W., Yang C.-H., Wang E.-C., . Synthesis of certain benzoheterocyclic compounds from 2-hydroxyacetophenone via cyclization and ring-closing metathesis. J. Chin. Chem. Soc.. 2005;52:159-167.
[Google Scholar]

[66] Ishizuka N., Matsumura K.-I., Sakai K., Fujimoto M., Mihara S.-I., Yamamori T., . Structure–activity relationships of a novel class of endothelin-a receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4-(4-methoxyphenyl)-2H-chromene-3-carboxylic acid (S-1255). 1. Study on structure–activity relationships and basic structure crucial for ETA antagonism. J. Med. Chem.. 2002;45:2041-2055.
[Google Scholar]

[67] Jayashree B.S., Thejaswini J.C., Nayak Y., Kumar D.V., . Synthesis of novel flavone acyl esters and correlation of log P value with antioxidant and antimicrobial activity. Asian J. Chem.. 2010;22:1055-1066.
[Google Scholar]

[68] Jones R.M., Van D.W.R.W., Lindsey C.C., Hoarau C., Ung T., Pettus T.R.R., . A mild anionic method for generating o-quinone methides: facile preparations of ortho-functionalized phenols. J. Org. Chem.. 2001;66:3435-3441.
[Google Scholar]

[69] Kabbe H.-J., Widdig A., . Synthesis and reactions of 4-chromanones. Angew. Chem. Int. Ed.. 1982;21:247-256.
[Google Scholar]

[70] Kallan N.C., Spencer K.L., Blake J.F., Xu R., Heizer J., Bencsik J.R., Mitchell I.S., Gloor S.L., Martinson M., Risom T., Gross S.D., Morales T.H., Wu W.-I., Vigers G.P.A., Brandhuber B.J., Skelton N.J., . Discovery and SAR of spirochromane Akt inhibitors. Bioorg. Med. Chem. Lett.. 2011;21:2410-2414.
[Google Scholar]

[71] Keshk E.M., . Benzofuranyl-pyran-2-ones, -pyridazines, and -pyridones from naturally occurring furochromones (visnagin and khellin) Heteroatom Chem.. 2004;15:85-91.
[Google Scholar]

[72] Khanna R.N., Singh K.P., Sharma J., . Study in crossover Fries migration. Org. Prep. Proced. Int.. 1992;24:687-690.
[Google Scholar]

[73] Kim J.N., Im Y.J., Kim J.M., . Synthesis of ortho-hydroxyacetophenone derivatives from Baylis-Hillman acetates. Tetrahedron Lett.. 2002;43:6597-6600.
[Google Scholar]

[74] Kiyama, R., Kanda, Y., Tada, Y., Fujishita, T., Kawasuji, T., Takechi, S., Fuji, M., 2003. Preparation of Heterocyclic Compounds as Integrase Inhibiting Antiviral Agents. Patent JP 2009161556.

[75] Klinger H., Kolvenbach W., . Formation of acetylquinol from acetaldehyde and quinone in sunlight. Ber. 1898;31:1214-1216.
[Google Scholar]

[76] Kloetzel M.C., Dayton R.P., Abadir B.Y., . Synthetic analogs of cortical hormones. I. Homogentisic acid and α,2,5-trihydroxyacetophenone derivatives from 2,5-diacetoxy-α-diazoacetophenone. J. Org. Chem.. 1955;20:38-49.
[Google Scholar]

[77] Kneppe H., Schneider F., . Rotational viscosity coefficients γ₁ for mixtures of nematic liquid crystals. Mol. Cryst. Liq. Cryst.. 1983;97:219-230.
[Google Scholar]

[78] Ko H.-H., Tsao L.-T., Yu K.-L., Liu C.-T., Wang J.-P., Lin C.-N., . Structure–activity relationship studies on chalcone derivatives the potent inhibition of chemical mediators release. Bioorg. Med. Chem.. 2003;11:105-111.
[Google Scholar]

[79] Kolla S.R., Lee Y.R., . Ca(OH)₂-mediated efficient synthesis of 2-amino-5-hydroxy-4H-chromene derivatives with various substituents. Tetrahedron. 2011;67:8271-8275.
[Google Scholar]

[80] Konieczny M.T., Maciejewski G., Konieczny W., . Selectivity adjustment in the cleavage of allyl phenyl and methyl phenyl ethers with boron trifluoride-methyl sulfide complex. Synthesis 2005:1575-1577.
[Google Scholar]

[81] Konishi F., Esaki S., Kamiya S., . Synthesis of flavonoid glycosides. Part XI. Synthesis and taste of some flavanone and dihydrochalcone glycosides in which carbohydrate moieties are located at differing positions of the aglycons. Agric. Biol. Chem. 1983:1419-1429.
[Google Scholar]

[82] Koskelainen, T., Otsomaa, L., Karjalainen, A., Kotovuori, P., Tenhunen, J., Rasku, S., Nore, P., Tiainen, E., Toermaekangas, O., 2004. Preparation of Phenyl Chromans, Benzo[1,4]dioxins, Indans, and Naphthalenes as Potent Inhibitors of Na⁺/Ca²⁺ Exchange Mechanism for Treatment of Arrhythmias. Patent US 20040235905.

[83] Kraus G.A., Melekhov A., . A direct route to acylhydroquinones from α-keto acids and α-carboxamido acids. Tetrahedron Lett.. 1998;39:3957-3960.
[Google Scholar]

[84] Kupcewicz B., Jarzęcki A.A., Małecka M., Krajewska U., Rozalski M., . Cytotoxic activity of substituted chalcones in terms of molecular electronic properties. Bioorg. Med. Chem. Lett.. 2014;24:4260-4265.
[Google Scholar]

[85] Lal, B., Gangopadhyay, A.K., Rao, V.V.S.V., Gupte, R.D., Gole, G.V., Kulkarni-Almeida, A., Krishnan, S., Panicker, R.B., Pinto, D.S.E., 2010. Preparation of Fused Bicyclic Compounds, in Particular 1-Oxo-1,3-dihydroisoindole Derivatives, as Fibrinogen Receptor Antagonists and Their Use for Treating Thrombotic and Other Diseases. Patent US 20100256161.

[86] Lamba M.S., Kumar S., Makrandi J.K., . One pot synthesis of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones by modified Baker–Venkataraman transformation using microwave irradiation. J. Chem. Res. 2006:133-134.
[Google Scholar]

[87] Le B.B., Windh R.T., Ajello C.W., Leister L.K., Gu M., Chu G.-H., Tuthill P.A., Barker W.M., Koblish M., Wiant D.D., Graczyk T.M., Belanger S., Cassel J.A., Feschenko M.S., Brogdon B.L., Smith S.A., Christ D.D., Derelanko M.J., Kutz S., Little P.J., DeHaven R.N., DeHaven-Hudkins D.L., Dolle R.E., . Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4′-piperidine]-4-yl)benzamide (ADL5859) J. Med. Chem.. 2008;51:5893-5896.
[Google Scholar]

[88] Legoabe L.J., Petzer A., Petzer J.P., . Selected chromone derivatives as inhibitors of monoamine oxidase. Bioorg. Med. Chem. Lett.. 2012;22:5480-5484.
[Google Scholar]

[89] Letourneau, J.J., Paradkar, V., Ohlmeyer, M.H.J., Dillard, L.W., Baldwin, J.J., Riviello, C.M., Wong, A., Rong, Y., 2005. Nitrogen Heterocycle Biaryls for Osteoporosis and Other Diseases. Patent US 2005222203.

[90] Lim S.S., Jung S.H., Ji J., Shin K.H., Keum S.R., . Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. J. Pharm. Pharmacol.. 2001;53:653-668.
[Google Scholar]

[91] Lindemann H., Romanoff S., . Ring closure of acetyloximes of aromatic o-hydroxyketones. J. Prakt. Chem.. 1929;122:214-231.
[Google Scholar]

[92] Lingam, V.S.P.R., Thomas, A., Khatik, J.Y., Khairatkar, J.N., Kattige, V.G., 2010. Preparation of Chromane Derivatives as TRPV3 Modulators for Treating Pain, Inflammation and Other Disorders. Patent WO 2010128038.

[93] Lyssikatos, J.P., Marmsater, F.P., Zhao, Q., Greschuk, J.M., 2007. Diarylamines as ErbB Inhibitors, Their Preparation, Pharmaceutical Compositions, and Use in Therapy. Patent WO 2007059257.

[94] Ma L., Yang Z., Li C., Zhu Z., Shen X., Hu L., . Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1) J. Enzyme Inhib. Med. Chem.. 2011;26:643-648.
[Google Scholar]

[95] Mandlik P.R., Aswar A.S., . Schiff base metal complexes of chromium(III), manganese(III), iron(III), oxovanadium(IV), zirconium(IV) and dioxouranium(VI) Pol. J. Chem.. 2003;77:129-135.
[Google Scholar]

[96] Manrao M.R., Kohli S., Kalsi P.S., Sharma R.C., Jhooty J.S., . Synthesis and antifungal activity of coumarinimides. Indian J. Chem. Sect. B. 1984;23:1130-1132.
[Google Scholar]

[97] Mays J.R., Hill S.A., Moyers J.T., Blagg B.S.J., . The synthesis and evaluation of flavone and isoflavone chimeras of novobiocin and derrubone. Bioorg. Med. Chem.. 2010;18:249-266.
[Google Scholar]

[98] Mitchell D., Doecke C.W., Hay L.A., Koenig T.M., Wirth D.D., . Ortho-hydroxyl assisted deoxygenation of phenones. Regiochemical control in the synthesis of monoprotected resorcinols and related polyphenolic hydroxyl systems. Tetrahedron Lett.. 1995;36:5335-5338.
[Google Scholar]

[99] Miyamura H., Shiramizu M., Matsubara R., Kobayashi S., . Aerobic oxidation of hydroquinone derivatives catalyzed by polymer-incarcerated platinum catalyst. Angew. Chem. Int. Ed.. 2008;47:8093-8095.
[Google Scholar]

[100] Miyazawa T., Hamada M., Morimoto R., Murashima T., Yamada T., . Highly regioselective propanoylation of dihydroxybenzenes mediated by Candida antarctica lipase B in organic solvents. Tetrahedron Lett.. 2008;49:175-178.
[Google Scholar]

[101] Mizuguchi E., Takemoto M., Achiwa K., . An enzyme-catalyzed synthesis of natural α-tocopherol. Tetrahedron Asymmetry. 1993;4:1961-1964.
[Google Scholar]

[102] Mmutlane E.M., Michael J.P., Green I.R., de K.C.B., . The synthesis of ventiloquinone L, the monomer of cardinalin 3. Org. Biomol. Chem.. 2004;2:2461-2470.
[Google Scholar]

[103] Moghaddam F.M., Ghaffarzadeh M., Abdi-Oskoui S.H., . Tandem Fries reaction-conjugate addition under microwave irradiation in dry media. One-pot synthesis of flavanones. J. Chem. Res., Synop. 1999:574-575.
[Google Scholar]

[104] Moorthy N.S.H.N., Singh R.J., Singh H.P., Gupta S.D., . Synthesis, biological evaluation and in silico metabolic and toxicity prediction of some flavanone derivatives. Chem. Pharm. Bull.. 2006;54:1384-1390.
[Google Scholar]

[105] Mujica-Fernaud, T., Buchholz, H., Carola, C., Rautenberg, W., Sirrenberg, C., 2004. Preparation of Oxadiazolylchromones as Modulators of Tyrosine Kinase Signal Transduction. Patent EP 1426372.

[106] Müller H., Paul M., Hartmann D., Huch V., Blaesius D., Koeberle A., Werz O., Jauch J., . Total synthesis of myrtucommulone A. Angew. Chem. Int. Ed.. 2010;49:2045-2049.
[Google Scholar]

[107] Mutai P., Pavadai E., Wiid I., Ngwane A., Baker B., Chibale K., . Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin. Bioorg. Med. Chem. Lett.. 2015;25:2510-2513.
[Google Scholar]

[108] Naeimi H., Moradi L., . Microwave assisted direct ortho-acylation of phenol and naphthol derivatives by BF₃·(C₂H₅)₂O. Bull. Chem. Soc. Jpn.. 2005;78:284-287.
[Google Scholar]

[109] Naeimi H., Moradi L., . Regioselective ortho-acylation of phenol and naphthol derivatives catalyzed by FeCl₃ under microwave conditions. Russ. J. Org. Chem.. 2007;43:1757-1759.
[Google Scholar]

[110] Nair M.L.H.K., Shamla L.J., . Synthesis, spectral, thermal and antibacterial studies of copper(II) complexes of a Schiff base derived from 2,3-dimethyl-1-phenyl-4-aminopyrazol-5-one. Indian Chem. Soc.. 2009;86:913-919.
[Google Scholar]

[111] Nam N.-H., Kim Y., You Y.-J., Hong D.-H., Kim H.-M., Ahn B.-Z., . Cytotoxic 2′,5′-dihydroxychalcones with unexpected antiangiogenic activity. Eur. J. Med. Chem.. 2003;38:179-187.
[Google Scholar]

[112] Neelakantan S., Raman P.V., Tinabaye A., . A new and convenient synthesis of 4-methyl-3-phenylcoumarins and 3-phenylcoumarins. Indian J. Chem. Sect. B. 1982;21:256-267.
[Google Scholar]

[113] Nicolosi G., Piattelli M., Sanfilippo C., . Lipase-catalyzed regioselective protection of hydroxyl groups in aromatic dihydroxy aldehydes and ketones. Tetrahedron. 1993;49:3143-3148.
[Google Scholar]

[114] Niedermeyer T.H.J., Mikolasch A., Lalk M., . Nuclear amination catalyzed by fungal laccases: reaction products of p-hydroquinones and primary aromatic amines. J. Org. Chem.. 2005;70:2002-2008.
[Google Scholar]

[115] Nussbaumer P., Lehr P., Billich A.J., . 2-Substituted 4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase. Med. Chem.. 2002;45:4310-4320.
[Google Scholar]

[116] Oganesyan E.T., Vasilenko Y.K., Khachatryan M.M., Pyshchev A.I., . Synthesis of flavone derivatives having hypolipidemic activities. Khim.-Farm. Zh.. 1989;23:1353-1356.
[Google Scholar]

[117] Park H.R., Park K.-S., Chong Y., . 2-Arylmethylaminomethyl-5,6-dihydroxychromone derivatives with selective anti-HCV activity. Bioorg. Med. Chem. Lett.. 2011;21:3202-3205.
[Google Scholar]

[118] Parveen M., Ali A., Alam M., Khan A., Ahmad A., . Synthesis, characterization, biological evaluation and in silico screening of oxadiazinanones. Med. Chem. Res.. 2013;22:3085-3095.
[Google Scholar]

[119] Paul S., Nanda P., Gupta R., Loupy A., . Zinc mediated Friedel-Crafts acylation in solvent-free conditions under microwave irradiation. Synthesis 2003:2877-2881.
[Google Scholar]

[120] Paul S., Nanda P., Gupta R., . Synthesis of α-bromoalkanones using urea–hydrogen peroxide complex and sodium bromide over silica gel–acetic acid. Indian J. Chem. Sect. B. 2005;44:184-187.
[Google Scholar]

[121] Pearce B.C., Parker R.A., Deason M.E., Dischino D.D., Gillespie E., Qureshi A.A., Wright J.J.K., Volk K., . Inhibitors of cholesterol biosynthesis. 2. hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogs of the tocotrienols. J. Med. Chem.. 1994;37:526-541.
[Google Scholar]

[122] Petrov M.L., Androsov D.A., Abramov M.A., Abramova I.P., Dehaen W., Lyakhovetskii Y.I., . Synthesis and reactivity of 5- and 6-hydroxybenzo[b]furan-2-selenolates. Russ. J. Org. Chem.. 2006;42:1521-1527.
[Google Scholar]

[123] Petrov M.L., Dehaen W., Abramov M.A., Abramova I.P., Androsov D.A., . 4-(2-Hydroxyaryl)-1,2,3-thiadiazoles as a source of 2-benzofuranthiolates. Russ. J. Org. Chem.. 2002;38:1510-1518.
[Google Scholar]

[124] Pillay A., Rousseau A.L., Fernandes M.A., de Koning C.B., . Wacker oxidation methodology for the synthesis of the benzo-fused acetal core of marticin. Tetrahedron. 2012;68:7116-7121.
[Google Scholar]

[125] Qin D.-D., Yang Z.-Y., Li T.-R., Qi G.-F., . DNA-binding study of nickel(II) and zinc(II) complexes with two novel chromenone-based Schiff-base ligands. Helv. Chim. Acta. 2009;92:525-535.
[Google Scholar]

[126] Rajakumar P., Mohammed A.R.A., Balu P.M., Murugesan K., . Synthesis, characterization, and anti-bacterial efficacy of some novel cyclophane amide. Bioorg. Med. Chem.. 2006;14:7458-7467.
[Google Scholar]

[127] Rane R.A., Sahu N.U., Gutte S.D., Mahajan A.A., Shah C.P., Bangalore P., . Synthesis and evaluation of novel marine bromopyrrole alkaloid-based hybrids as anticancer agents. Eur. J. Med. Chem.. 2013;63:793-799.
[Google Scholar]

[128] Ravichandran S., Singh N., Donnelly D., Migliore M., Johnson P., Fishwick C., Luke B.T., Martin B., Maudsley S., Fugmann S.D., Moaddel R., . Pharmacophore model of the quercetin binding site of the SIRT6 protein. J. Mol. Graph. Modell.. 2014;49:38-46.
[Google Scholar]

[129] Roma G., Di B.M., Carrieri A., Grossi G., Leoncini G., Grazia S.M., Carotti A., . Coumarin, chromone, and 4(3H)-pyrimidinone novel bicyclic and tricyclic derivatives as antiplatelet agents: synthesis, biological evaluation, and comparative molecular field analysis. Bioorg. Med. Chem.. 2003;11:123-138.
[Google Scholar]

[130] Roma G., Di B.M., Grossi G., Piras D., Leoncini G., Bruzzese D., Signorello M.G., Fossa P., Mosti L., . Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two most effective compounds described and molecular modeling study on their interactions with phosphodiesterase 3A catalytic site. J. Med. Chem.. 2007;50:2886-2895.
[Google Scholar]

[131] Rosenmund K.W., Lohfert H., . Synthesis of polyphenol ketones. Ber. Dtsch. Chem. Ges. B. 1928;61B:2601-2607.
[Google Scholar]

[132] Ruchirawat S., Mutarapat T., . An efficient synthesis of lamellarin alkaloids: synthesis of lamellarin G trimethyl ether. Tetrahedron Lett.. 2001;42:1205-1208.
[Google Scholar]

[133] Russell A., Clark S.F., . Constitution of natural tannins. VI. Coloring matters derived from 2,5-dihydroxyacetophenone. J. Am. Chem. Soc.. 1939;61:2651-2658.
[Google Scholar]

[134] Russell A., Happoldt W.B. Jr., . Constitution of natural tannins. VIII. Coloring matters derived from anthracene-9-aldehyde. J. Am. Chem. Soc.. 1942;64:1101-1103.
[Google Scholar]

[135] Sakamoto, K., Okuyama, K., 2014. Polymerizable Compound, Polymerizable Composition, Polymer, and Optically Anisotropic Body. Patent EP 2719683.

[136] Sakamoto, K., Okuyama, K., 2014. Polymerizable Compound, Polymerizable Composition, Polymer, and Optically Anisotropic Material. Patent EP 2703385.

[137] Salama T.A., Ismail M.A., Khalil A.-G.M., Elmorsy S.S., . Silicon-assisted O-heterocyclic synthesis: mild and efficient one-pot syntheses of (E)-3-benzylideneflavanones, coumarin-3-carbonitriles/carboxamides, and benzannulated spiropyran derivatives. Arkivoc 2012:242-253.
[Google Scholar]

[138] Salavati-Niasari M., Fereshteh Z., Davar F., . Synthesis of cobalt nanoparticles from [bis(2-hydroxyacetophenato)cobalt(II)] by thermal decomposition. Polyhedron. 2009;28:1065-1068.
[Google Scholar]

[139] Sanchez-Viesca F., Berros M., Gomez M.R., . Intramolecular weak hydrogen bonds in substituted 4-arylthiazoles. Heterocycl. Commun.. 2003;9:165-170.
[Google Scholar]

[140] Sato S., Watanabe T., Kumagai H., Kitamura N., Matsuba S., Kumazawa T., Onodera J.-I., Suzuki M., . Convenient synthesis of 1,6,7,8-substituted 2-(3′,4′-substituted-phenyl)-4-quinolones via a 4-ethoxyflavylium salt. J. Heterocycl. Chem.. 1999;36:1189-1193.
[Google Scholar]

[141] Schönberg A., Badran N., Starkowsky N.A., . Furo-chromones and -coumarins. VII. Degradation of visnagin, khellin and related substances; experiments with chromic acid and hydrogen peroxide; and a synthesis of eugenitin. J. Am. Chem. Soc.. 1953;75:4992-4995.
[Google Scholar]

[142] Sharghi H., Kaboudin B., . Alumina in methanesulfonic acid (AMA) as a new efficient reagent for direct acylation of phenol derivatives and Fries rearrangement. A convenient synthesis of o-hydroxyarylketones. J. Chem. Res. 1998:2678-2695. (Miniprint)
[Google Scholar]

[143] Sharma S.C., Swami M.P., Sharma R.C., . Nitrogen heterocyclic analogs of cannabinoids. Part I: synthesis of 6H-indolo[1,2-c][1,3]benzoxazine systems and evaluation of their biological activities. J. Indian Chem. Soc.. 1983;60:1002-1004.
[Google Scholar]

[144] Singh H.P., Chauhan C.S., Pandeya S.N., Sharma C.S., . Chalconsemicarbazone: a new scaffold for antiepileptic drug discovery. J. Chil. Chem. Soc.. 2010;55:103-106.
[Google Scholar]

[145] Sircar I., Hoefle M., Maxwell R.E., . Phenylenebis(oxy)bis[2,2-dimethylpentanoic acids]: agents that elevate high-density lipoproteins. J. Med. Chem.. 1983;26:1020-1027.
[Google Scholar]

[146] Srimal R.C., Kar K., . Synthesis of 2,4-, 2,5- and 2,6-bis[3-substituted amino(propoxy/2-hydroxypropoxy)]acetophenones as biodynamic agents. Indian J. Chem. Sect. B. 1983;22:140-145.
[Google Scholar]

[147] Summa V., Petrocchi A., Pace P., Matassa V.G., De F.R., Altamura S., Tomei L., Koch U., Neuner P., . Discovery of α,γ-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. J. Med. Chem.. 2004;47:14-17.
[Google Scholar]

[148] Takabatake T., Miyazawa T., Kojo M., Hasegawa M., . Synthesis of phenazine 5,10-dioxides from benzofuroxan catalyzed by molecular sieves. Heterocycles. 2000;53:2151-2162.
[Google Scholar]

[149] Thapliyal P.C., Aggarwal L.K., . Thermal cross Fries acyl and benzoyl migrations from aromatic diesters to phenols. Indian J. Chem. Sect. B. 2000;39:706-708.
[Google Scholar]

[150] Tripathi A.K., Koul S., Taneja S.C., . Microwave-assisted facile and efficient synthesis of benzopyran. Indian J. Chem. Sect. B. 2009;48:301-304.
[Google Scholar]

[151] Tu Q.-D., Li D., Sun Y., Han X.-Y., Yi F., Sha Y., Ren Y.-L., Ding M.-W., Feng L.-L., Wan J., . Design and syntheses of novel N′-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide as inhibitors of cyanobacterial fructose-1,6-sedoheptulose-1,7-bisphosphatase. Bioorg. Med. Chem.. 2013;21:2826-2831.
[Google Scholar]

[152] Uchil V.R., Joshi V., . Montmorillonite K10-AlCl3 catalyzed enolization. A bifunctional system for selective bromination of hydroxyacetophenones. Indian J. Chem. Sect. B. 2003;42:408-411.
[Google Scholar]

[153] Vandenberghe A., Willems J.F., . Sulfonation of alkyl hydroquinones. B. Soc. Chim. Belg.. 1965;74:397-406.
[Google Scholar]

[154] Vasquez-Martinez Y., Ohri R.V., Kenyon V., Holman T.R., Sepulveda-Boza S., . Structure–activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. Bioorg. Med. Chem.. 2007;15:7408-7425.
[Google Scholar]

[155] Veibel S., Schmidt H.W., . Diagnostic value of the titration curves of the p-carboxyphenylhydrazones of hydroxy-substituted aromatic aldehydes and ketones. Acta Chem. Scand.. 1948;2:545-549.
[Google Scholar]

[156] Verheggen F., Ryne C., Olsson P.O.C., Arnaud L., Lognay G., Hoegberg H.E., Persson D., Haubruge E., Loefstedt C., . Electrophysiological and behavioral activity of secondary metabolites in the confused flour beetle, Tribolium confusum. J. Chem. Ecol.. 2007;33:525-539.
[Google Scholar]

[157] Verma J.K., Verma G.S.P., . Dimeric copper(II), nickel(II) and cobalt(II) complexes of tridentate ONN donor ligands. J. Indian Chem. Soc.. 1983;60:786-787.
[Google Scholar]

[158] Vyas G.N., Shah N.M., . Chalcones from quinacetophenone. J. Indian Chem. Soc.. 1949;26:273-276.
[Google Scholar]

[159] Wellington K.W., Steenkamp P., Brady D., . Diamination by N-coupling using a commercial laccase. Bioorg. Med. Chem.. 2010;18:1406-1414.
[Google Scholar]

[160] Willstaedt H., Michaelis M., . 1,4-Dihydroxy-2-acetylanthraquinone. Sven. Kem. Tidskr.. 1938;50:274-278.
[Google Scholar]

[161] Wissner A., Carroll M.L., Green K.E., Kerwar S.S., Pickett W.C., Schaub R.E., Torley L.W., Wrenn S., Kohler C.A., . Analogs of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor. J. Med. Chem.. 1992;35:1650-1662.
[Google Scholar]

[162] Witiak D.T., Kim S.K., Tehim A.K., Sternitzke K.D., McCreery R.L., Kim S.U., Feller D.R., Romstedt K.J., Kamanna V.S., Newman H.A.I., . Synthetic aci-reductones. 3,4-Dihydroxy-2H-1-benzopyran-2-ones and their cis- and trans-4a,5,6,7,8,8a-hexahydro diastereomers. Antiaggregatory, antilipidemic, and redox properties compared to the 4-substituted 2-hydroxytetronic acids. J. Med. Chem.. 1988;31:1437-1445.
[Google Scholar]

[163] Won S.-J., Liu C.-T., Tsao L.-T., Weng J.-R., Ko H.-H., Wang J.-P., Lin C.-N., . Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur. J. Med. Chem.. 2005;40:103-112.
[Google Scholar]

[164] Wu S.-Y., Ito S., Eto M., . Metabolic formation of 4-methyl-4H-1,3,2-benzodioxaphosphorins from bis(o-ethylphenyl) phenylphosphonates in house flies. Agric. Biol. Chem.. 1987;51:2935-2942.
[Google Scholar]

[165] Wymann W.E., Davis R., Patterson J.W. Jr., Pfister J.R., . Selective alkylations of certain phenolic and enolic functions with lithium carbonate-alkyl halide. Synth. Commun.. 1988;18:1379-1384.
[Google Scholar]

[166] Yamaguchi S., Saitoh A., Kawase Y., . The revised structure of a dihydrobenzofuran derivative isolated from Lasiolaena morii. Bull. Chem. Soc. Jpn.. 1986;59:3983-3984.
[Google Scholar]

[167] Yamato M., Hashigaki K., Tsutsumi A., Tasaka K., . Synthesis and structure–activity relationship of spiro[isochroman-piperidine] analogs for inhibition of histamine release. II. Chem. Pharm. Bull.. 1981;29:3494-3498.
[Google Scholar]

[168] Zbancioc A.M., Miron A., Tuchilus C., Rotinberg P., Mihai C.T., Mangalagiu I.I., Zbancioc G., . Synthesis and in vitro analysis of novel dihydroxyacetophenone derivatives with antimicrobial and antitumor activities. Med. Chem.. 2014;10:476-483.
[Google Scholar]

[169] Zbancioc G.N., Zbancioc A.M.V., Mantu D., Miron A., Tanase C., Mangalagiu I.I., . Ultrasound-assisted synthesis of highly functionalized acetophenone derivatives in heterogeneous catalysis. Rev. Roum. Chim.. 2010;55:983-987.
[Google Scholar]

[170] Zhao H., Brandt G.E., Galam L., Matts R.L., Blagg B.S.J., . Identification and initial SAR of silybin: an Hsp90 inhibitor. Bioorg. Med. Chem. Lett.. 2011;21:2659-2664.
[Google Scholar]

[171] Zhao W., Sun J., Xiang H., Zeng Y.-Y., Li X.-B., Xiao H., Chen D.-Y., Ma R.-L., . Synthesis and biological evaluation of new flavonoid fatty acid esters with anti-adipogenic and enhancing glucose consumption activities. Bioorg. Med. Chem.. 2011;19:3192-3203.
[Google Scholar]

Quinacetophenone: A simple precursor to privileged organic motifs

Abstract

Keywords

Hydroxyacetophenone

Chalcone

Chromone

Flavone

Chromanone

Coumarin

1 Introduction

2 Preparation methods

2.1 Friedel–Crafts acetylation

2.2 Fries rearrangement

2.3 Hoesch reaction

2.4 From benzoquinone

3 Reactions

3.1 Hydroxyl moiety based reactions

3.1.1 Alkylation

3.1.2 Acylation

3.2 Active methylene moiety based reactions

3.2.1 Mannich reaction

3.2.2 Claisen–Schmidt reaction

3.2.3 Synthesis of α,γ-diketo acid (DKA)

3.2.4 Synthesis of β-diketone

3.2.5 Synthesis of β-hydroxy carbonyl compound

3.2.6 Bromination

3.3 Carbonyl moiety based reactions

3.3.1 Acetal formation

3.3.2 Horner–Emmons–Wadsworth reaction

3.3.3 Condensation reactions

3.3.4 Synthesis of oxadiazinanone derivative

3.3.5 Reduction

3.4 Methyl ketone moiety based reactions

3.4.1 Synthesis of azoles

3.4.2 Synthesis of indole heterocycle

3.5 Hydroxyacetyl moiety based reactions

3.5.1 Synthesis of chromones

3.5.2 Synthesis of chromanones

3.5.3 Synthesis of flavonoids

3.6 Electrophilic substitution reactions

3.6.1 Nitration

3.6.2 Halogenation

3.7 Miscellaneous reactions

3.7.1 Synthesis of phenazine derivative

3.7.2 Synthesis of quinone derivatives

3.7.3 Synthesis of benzofurans

3.7.4 Synthesis of coumarins

4 Conclusion

References

Suggested read for related articles: